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Study to Investigate Idelalisib in Combination With Chemotherapeutic Agents, Immunomodulatory Agents and Anti-CD20 Monoclonal Antibody (mAb) in Participants With Relapsed or Refractory Indolent B-cell Non-Hodgkin's Lymphoma, Mantle Cell Lymphoma or Chronic Lymphocytic Leukemia

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ClinicalTrials.gov Identifier: NCT01088048
Recruitment Status : Completed
First Posted : March 17, 2010
Results First Posted : March 18, 2021
Last Update Posted : March 18, 2021
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Indolent Non-Hodgkin's Lymphoma
Chronic Lymphocytic Leukemia
Mantle Cell Lymphoma
Interventions Drug: Idelalisib
Drug: Rituximab
Drug: Bendamustine
Drug: Ofatumumab
Drug: Fludarabine
Drug: Everolimus
Drug: Bortezomib
Drug: Chlorambucil
Drug: Lenalidomide
Enrollment 241
Recruitment Details Participants were enrolled at study sites in United States. The first participant was screened on 25 March 2010. The last study visit occurred on 28 April 2015.
Pre-assignment Details 277 participants were screened. Per prespecified analysis, participants were grouped by disease (chronic lymphocytic leukemia, indolent non-Hodgkin lymphoma, mantle cell lymphoma) and by treatment regimen (cohort).
Arm/Group Title Idelalisib + Rituximab Idelalisib + Bendamustine Idelalisib + Everolimus Idelalisib + Bortezomib Idelalisib + Rituximab + Bendamustine Idelalisib + Ofatumumab Idelalisib + Fludarabine Idelalisib + Chlorambucil Idelalisib + Rituximab + Chlorambucil Idelalisib + Rituximab + Lenalidomide
Hide Arm/Group Description

Participants with chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin lymphoma (iNHL) received treatments as follows:

Cohort 1a: Idelalisib (IDELA) 100 mg orally twice daily (BID) on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 intravenously (IV) on Days 1, 8, 15 & 22, Cycles 1 & 2

Cohort 2a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Cohort 3e: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Cohort 4a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle, starting Cycle 2 Day 1 with the 5th dose of rituximab + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Participants with CLL and iNHL received treatments as follows:

Cohort 1b: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 2b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3f: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3g: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 4b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle starting Cycle 2, Day 3 (after the Cycle 2 bendamustine dosing) + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Participants with mantle cell lymphoma (MCL) received treatments as follows:

Cohort 5a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + everolimus 10 mg orally once daily on Days 1 - 28 of each 28-day cycle

Participants with MCL received treatments as follows:

Cohort 5b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 8 & 15 of each 28-day cycle

Participants with CLL, iNHL and MCL received treatments as follows:

Cohort 3a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle from Cycles 1 - 6

Cohort 5c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Participants with CLL received treatments as follows:

Cohort 3c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + ofatumumab 12 doses (300 mg (Day 1 or Day 2, Dose 1), followed 1 week later by 1,000 mg weekly for 7 doses (Doses 2 - 8), followed 5 weeks later by 1,000 mg every 4 weeks for 4 doses (Doses 9 - 12))

Participants with CLL received treatments as follows:

Cohort 3d: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + fludarabine 40 mg/m^2 orally on Days 1 - 5 of each 28-day cycle, Cycles 1 - 6

Participants with CLL received treatments as follows:

Cohort 6a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12

Participants with CLL received treatments as follows:

Cohort 6b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12

Participants with CLL and iNHL received treatments as follows:

Cohort 7a: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 5 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Cohort 7b: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 10 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Cohort 7c: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 20 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Period Title: Overall Study
Started 51 51 18 18 33 21 12 15 15 7
Participants With CLL 19 18 0 0 15 21 12 15 14 1
Participants With Indolent NHL 32 33 0 0 14 0 0 0 1 6
Participants With MCL 0 0 18 18 4 0 0 0 0 0
Completed 29 24 4 4 16 10 6 10 8 3
Not Completed 22 27 14 14 17 11 6 5 7 4
Reason Not Completed
Adverse Event             7             9             7             5             6             3             3             0             2             2
Withdrew Consent             1             1             1             1             2             1             0             2             2             1
Concomitant Medication Prohibited             1             0             0             0             0             0             0             0             0             0
Investigator Request             2             2             0             0             3             1             1             0             0             0
Patient Non-compliance             0             1             0             0             0             0             0             0             0             0
Disease Progression             7             4             3             5             3             3             2             1             0             0
Death             1             5             3             3             1             3             0             0             3             1
Other             3             5             0             0             2             0             0             2             0             0
Arm/Group Title Idelalisib + Rituximab Idelalisib + Bendamustine Idelalisib + Everolimus Idelalisib + Bortezomib Idelalisib + Rituximab + Bendamustine Idelalisib + Ofatumumab Idelalisib + Fludarabine Idelalisib + Chlorambucil Idelalisib + Rituximab + Chlorambucil Idelalisib + Rituximab + Lenalidomide Total
Hide Arm/Group Description

Participants with CLL and iNHL received treatments as follows:

Cohort 1a: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15 & 22, Cycles 1 & 2

Cohort 2a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Cohort 3e: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Cohort 4a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle, starting Cycle 2 Day 1 with the 5th dose of rituximab + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Participants with CLL and iNHL received treatments as follows:

Cohort 1b: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 2b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3f: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3g: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 4b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle starting Cycle 2, Day 3 (after the Cycle 2 bendamustine dosing) + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Participants with MCL received treatments as follows:

Cohort 5a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + everolimus 10 mg orally once daily on Days 1 - 28 of each 28-day cycle

Participants with MCL received treatments as follows:

Cohort 5b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 8 & 15 of each 28-day cycle

Participants with CLL, iNHL and MCL received treatments as follows:

Cohort 3a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle from Cycles 1 - 6

Cohort 5c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Participants with CLL received treatments as follows:

Cohort 3c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + ofatumumab 12 doses (300 mg (Day 1 or Day 2, Dose 1), followed 1 week later by 1,000 mg weekly for 7 doses (Doses 2 - 8), followed 5 weeks later by 1,000 mg every 4 weeks for 4 doses (Doses 9 - 12))

Participants with CLL received treatments as follows:

Cohort 3d: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + fludarabine 40 mg/m^2 orally on Days 1 - 5 of each 28-day cycle, Cycles 1 - 6

Participants with CLL received treatments as follows:

Cohort 6a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12

Participants with CLL received treatments as follows:

Cohort 6b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12

Participants with CLL and iNHL received treatments as follows:

Cohort 7a: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 5 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Cohort 7b: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 10 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Cohort 7c: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 20 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Total of all reporting groups
Overall Number of Baseline Participants 51 51 18 18 33 21 12 15 15 7 241
Hide Baseline Analysis Population Description
The intent-to-treat (ITT) analysis set included participants who received at least 1 dose of study drug (Idelalisib or combination drugs). Per prespecified analysis, participants were grouped by disease (CLL, iNHL, MCL) and by treatment regimen (cohort).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 51 participants 51 participants 18 participants 18 participants 33 participants 21 participants 12 participants 15 participants 15 participants 7 participants 241 participants
65  (10.1) 61  (11.2) 69  (7.1) 72  (6.0) 60  (8.3) 66  (9.7) 69  (7.1) 63  (7.8) 68  (10.0) 61  (8.3) 64  (9.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 51 participants 18 participants 18 participants 33 participants 21 participants 12 participants 15 participants 15 participants 7 participants 241 participants
Female
16
  31.4%
21
  41.2%
7
  38.9%
3
  16.7%
12
  36.4%
6
  28.6%
4
  33.3%
1
   6.7%
4
  26.7%
2
  28.6%
76
  31.5%
Male
35
  68.6%
30
  58.8%
11
  61.1%
15
  83.3%
21
  63.6%
15
  71.4%
8
  66.7%
14
  93.3%
11
  73.3%
5
  71.4%
165
  68.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 51 participants 18 participants 18 participants 33 participants 21 participants 12 participants 15 participants 15 participants 7 participants 241 participants
White/Caucasian 42 45 16 14 29 20 8 14 15 6 209
Black or African American 2 3 0 0 1 0 1 1 0 1 9
Asian 5 1 1 2 1 0 1 0 0 0 11
Other 0 0 0 0 0 1 0 0 0 0 1
Not Reported 2 2 1 2 2 0 2 0 0 0 11
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 51 participants 18 participants 18 participants 33 participants 21 participants 12 participants 15 participants 15 participants 7 participants 241 participants
Hispanic or Latino 0 2 0 1 0 0 0 1 0 0 4
Not Hispanic or Latino 51 49 18 17 31 21 11 14 15 7 234
Missing 0 0 0 0 2 0 1 0 0 0 3
1.Primary Outcome
Title Duration of Exposure to IDELA
Hide Description Duration of exposure to IDELA was summarized using descriptive statistics.
Time Frame First dose date up to 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included participants who received at least 1 dose of study drug (idelalisib or combination drugs). Per prespecified analysis, participants for this outcome measure were grouped by disease and treatment regimen (cohort).
Arm/Group Title Idelalisib + Rituximab Idelalisib + Bendamustine Idelalisib + Everolimus Idelalisib + Bortezomib Idelalisib + Rituximab + Bendamustine Idelalisib + Ofatumumab Idelalisib + Fludarabine Idelalisib + Chlorambucil Idelalisib + Rituximab + Chlorambucil Idelalisib + Rituximab + Lenalidomide
Hide Arm/Group Description:

Participants with chronic CLL and iNHL received treatments as follows:

Cohort 1a: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15 & 22, Cycles 1 & 2

Cohort 2a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Cohort 3e: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Cohort 4a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle, starting Cycle 2 Day 1 with the 5th dose of rituximab + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Participants with CLL and iNHL received treatments as follows:

Cohort 1b: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 2b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3f: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3g: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 4b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle starting Cycle 2, Day 3 (after the Cycle 2 bendamustine dosing) + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Participants with MCL received treatments as follows:

Cohort 5a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + everolimus 10 mg orally once daily on Days 1 - 28 of each 28-day cycle

Participants with MCL received treatments as follows:

Cohort 5b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 8 & 15 of each 28-day cycle

Participants with CLL, iNHL and MCL received treatments as follows:

Cohort 3a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle from Cycles 1 - 6

Cohort 5c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Participants with CLL received treatments as follows:

Cohort 3c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + ofatumumab 12 doses (300 mg (Day 1 or Day 2, Dose 1), followed 1 week later by 1,000 mg weekly for 7 doses (Doses 2 - 8), followed 5 weeks later by 1,000 mg every 4 weeks for 4 doses (Doses 9 - 12))

Participants with CLL received treatments as follows:

Cohort 3d: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + fludarabine 40 mg/m^2 orally on Days 1 - 5 of each 28-day cycle, Cycles 1 - 6

Participants with CLL received treatments as follows:

Cohort 6a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12

Participants with CLL received treatments as follows:

Cohort 6b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12

Participants with CLL and iNHL received treatments as follows:

Cohort 7a: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 5 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Cohort 7b: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 10 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Cohort 7c: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 20 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Overall Number of Participants Analyzed 51 51 18 18 33 21 12 15 15 7
Mean (Standard Deviation)
Unit of Measure: months
8.1  (3.74) 7.6  (3.96) 4.2  (3.92) 5.1  (3.90) 8.0  (4.16) 8.3  (4.03) 8.9  (3.57) 8.8  (3.76) 8.7  (3.01) 7.7  (4.78)
2.Primary Outcome
Title Toxicity of Administration of IDELA
Hide Description Percentage of participants experiencing toxicities of administration of IDELA were measured according to the Common Terminology Criteria for Adverse Events v4.02
Time Frame First dose date up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the ITT analysis set were analyzed. Per prespecified analysis, participants for this outcome measure were grouped by disease and treatment regimen (cohort).
Arm/Group Title Idelalisib + Rituximab Idelalisib + Bendamustine Idelalisib + Everolimus Idelalisib + Bortezomib Idelalisib + Rituximab + Bendamustine Idelalisib + Ofatumumab Idelalisib + Fludarabine Idelalisib + Chlorambucil Idelalisib + Rituximab + Chlorambucil Idelalisib + Rituximab + Lenalidomide
Hide Arm/Group Description:

Participants with chronic CLL and iNHL received treatments as follows:

Cohort 1a: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15 & 22, Cycles 1 & 2

Cohort 2a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Cohort 3e: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Cohort 4a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle, starting Cycle 2 Day 1 with the 5th dose of rituximab + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Participants with CLL and iNHL received treatments as follows:

Cohort 1b: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 2b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3f: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3g: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 4b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle starting Cycle 2, Day 3 (after the Cycle 2 bendamustine dosing) + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Participants with MCL received treatments as follows:

Cohort 5a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + everolimus 10 mg orally once daily on Days 1 - 28 of each 28-day cycle

Participants with MCL received treatments as follows:

Cohort 5b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 8 & 15 of each 28-day cycle

Participants with CLL, iNHL and MCL received treatments as follows:

Cohort 3a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle from Cycles 1 - 6

Cohort 5c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Participants with CLL received treatments as follows:

Cohort 3c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + ofatumumab 12 doses (300 mg (Day 1 or Day 2, Dose 1), followed 1 week later by 1,000 mg weekly for 7 doses (Doses 2 - 8), followed 5 weeks later by 1,000 mg every 4 weeks for 4 doses (Doses 9 - 12))

Participants with CLL received treatments as follows:

Cohort 3d: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + fludarabine 40 mg/m^2 orally on Days 1 - 5 of each 28-day cycle, Cycles 1 - 6

Participants with CLL received treatments as follows:

Cohort 6a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12

Participants with CLL received treatments as follows:

Cohort 6b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12

Participants with CLL and iNHL received treatments as follows:

Cohort 7a: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 5 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Cohort 7b: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 10 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Cohort 7c: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 20 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Overall Number of Participants Analyzed 51 51 18 18 33 21 12 15 15 7
Measure Type: Number
Unit of Measure: percentage of participants
100.0 100.0 100.0 83.33 100.0 100.0 100.0 100.0 100.0 100.0
3.Secondary Outcome
Title Overall Response Rate
Hide Description

Overall Response Rate (ORR) was defined as the percentage of participants achieving a complete response (CR) or partial response (PR).

The response definitions were based on the following standard criteria established for each indication:

  • CLL: International Workshop on chronic lymphocytic leukemia (IWCLL),2008
  • iNHL & MCL: Cheson, 2007
Time Frame Up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the ITT analysis set were analyzed. Per prespecified analysis, participants for this outcome measure were grouped by disease and treatment regimen (cohort).
Arm/Group Title Idelalisib + Rituximab Idelalisib + Bendamustine Idelalisib + Everolimus Idelalisib + Bortezomib Idelalisib + Rituximab + Bendamustine Idelalisib + Ofatumumab Idelalisib + Fludarabine Idelalisib + Chlorambucil Idelalisib + Rituximab + Chlorambucil Idelalisib + Rituximab + Lenalidomide
Hide Arm/Group Description:

Participants with chronic CLL and iNHL received treatments as follows:

Cohort 1a: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15 & 22, Cycles 1 & 2

Cohort 2a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Cohort 3e: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Cohort 4a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle, starting Cycle 2 Day 1 with the 5th dose of rituximab + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Participants with CLL and iNHL received treatments as follows:

Cohort 1b: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 2b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3f: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3g: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 4b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle starting Cycle 2, Day 3 (after the Cycle 2 bendamustine dosing) + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Participants with MCL received treatments as follows:

Cohort 5a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + everolimus 10 mg orally once daily on Days 1 - 28 of each 28-day cycle

Participants with MCL received treatments as follows:

Cohort 5b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 8 & 15 of each 28-day cycle

Participants with CLL, iNHL and MCL received treatments as follows:

Cohort 3a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle from Cycles 1 - 6

Cohort 5c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Participants with CLL received treatments as follows:

Cohort 3c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + ofatumumab 12 doses (300 mg (Day 1 or Day 2, Dose 1), followed 1 week later by 1,000 mg weekly for 7 doses (Doses 2 - 8), followed 5 weeks later by 1,000 mg every 4 weeks for 4 doses (Doses 9 - 12))

Participants with CLL received treatments as follows:

Cohort 3d: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + fludarabine 40 mg/m^2 orally on Days 1 - 5 of each 28-day cycle, Cycles 1 - 6

Participants with CLL received treatments as follows:

Cohort 6a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12

Participants with CLL received treatments as follows:

Cohort 6b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12

Participants with CLL and iNHL received treatments as follows:

Cohort 7a: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 5 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Cohort 7b: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 10 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Cohort 7c: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 20 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Overall Number of Participants Analyzed 51 51 18 18 33 21 12 15 15 7
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
78.4
(64.7 to 88.7)
84.3
(71.4 to 93.0)
44.4
(21.5 to 69.2)
61.1
(35.7 to 82.7)
81.8
(64.5 to 93.0)
71.4
(47.8 to 88.7)
91.7
(61.5 to 99.8)
66.7
(38.4 to 88.2)
93.3
(68.1 to 99.8)
71.4
(29.0 to 96.3)
4.Secondary Outcome
Title Duration of Response
Hide Description Duration of response (DOR) was defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of disease progression or death from any cause.
Time Frame Up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the ITT analysis set with available data were analyzed. Per prespecified analysis, participants for this outcome measure were grouped by disease and treatment regimen (cohort).
Arm/Group Title Idelalisib + Rituximab Idelalisib + Bendamustine Idelalisib + Everolimus Idelalisib + Bortezomib Idelalisib + Rituximab + Bendamustine Idelalisib + Ofatumumab Idelalisib + Fludarabine Idelalisib + Chlorambucil Idelalisib + Rituximab + Chlorambucil Idelalisib + Rituximab + Lenalidomide
Hide Arm/Group Description:

Participants with chronic CLL and iNHL received treatments as follows:

Cohort 1a: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15 & 22, Cycles 1 & 2

Cohort 2a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Cohort 3e: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Cohort 4a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle, starting Cycle 2 Day 1 with the 5th dose of rituximab + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Participants with CLL and iNHL received treatments as follows:

Cohort 1b: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 2b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3f: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3g: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 4b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle starting Cycle 2, Day 3 (after the Cycle 2 bendamustine dosing) + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Participants with MCL received treatments as follows:

Cohort 5a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + everolimus 10 mg orally once daily on Days 1 - 28 of each 28-day cycle

Participants with MCL received treatments as follows:

Cohort 5b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 8 & 15 of each 28-day cycle

Participants with CLL, iNHL and MCL received treatments as follows:

Cohort 3a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle from Cycles 1 - 6

Cohort 5c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Participants with CLL received treatments as follows:

Cohort 3c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + ofatumumab 12 doses (300 mg (Day 1 or Day 2, Dose 1), followed 1 week later by 1,000 mg weekly for 7 doses (Doses 2 - 8), followed 5 weeks later by 1,000 mg every 4 weeks for 4 doses (Doses 9 - 12))

Participants with CLL received treatments as follows:

Cohort 3d: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + fludarabine 40 mg/m^2 orally on Days 1 - 5 of each 28-day cycle, Cycles 1 - 6

Participants with CLL received treatments as follows:

Cohort 6a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12

Participants with CLL received treatments as follows:

Cohort 6b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12

Participants with CLL and iNHL received treatments as follows:

Cohort 7a: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 5 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Cohort 7b: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 10 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Cohort 7c: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 20 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Overall Number of Participants Analyzed 40 43 8 11 27 15 11 10 14 5
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
5.6 [2] 
(1.1 to NA)
9.3
(4.9 to 9.3)
NA [3] 
(9.9 to NA)
NA [3] 
(9.4 to NA)
NA [3] 
(3.5 to NA)
NA [1] 
(NA to NA)
NA [3] 
(4.4 to NA)
NA [3] 
(1.3 to NA)
[1]
NA = Not Reached; too few events to estimate the median and the lower and upper limits of the confidence interval
[2]
NA = Not Reached; too few events to estimate the upper limit of the confidence interval
[3]
NA = Not Reached; too few events to estimate the median and the upper limit of the confidence interval
5.Secondary Outcome
Title Time to Response
Hide Description Time to response (TTR) was defined as the interval from the start of study drug to the first documentation of CR or PR.
Time Frame Up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the ITT analysis set with available data were analyzed. Per prespecified analysis, participants for this outcome measure were grouped by disease and treatment regimen (cohort).
Arm/Group Title Idelalisib + Rituximab Idelalisib + Bendamustine Idelalisib + Everolimus Idelalisib + Bortezomib Idelalisib + Rituximab + Bendamustine Idelalisib + Ofatumumab Idelalisib + Fludarabine Idelalisib + Chlorambucil Idelalisib + Rituximab + Chlorambucil Idelalisib + Rituximab + Lenalidomide
Hide Arm/Group Description:

Participants with chronic CLL and iNHL received treatments as follows:

Cohort 1a: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15 & 22, Cycles 1 & 2

Cohort 2a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Cohort 3e: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Cohort 4a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle, starting Cycle 2 Day 1 with the 5th dose of rituximab + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Participants with CLL and iNHL received treatments as follows:

Cohort 1b: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 2b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3f: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3g: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 4b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle starting Cycle 2, Day 3 (after the Cycle 2 bendamustine dosing) + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Participants with MCL received treatments as follows:

Cohort 5a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + everolimus 10 mg orally once daily on Days 1 - 28 of each 28-day cycle

Participants with MCL received treatments as follows:

Cohort 5b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 8 & 15 of each 28-day cycle

Participants with CLL, iNHL and MCL received treatments as follows:

Cohort 3a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle from Cycles 1 - 6

Cohort 5c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Participants with CLL received treatments as follows:

Cohort 3c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + ofatumumab 12 doses (300 mg (Day 1 or Day 2, Dose 1), followed 1 week later by 1,000 mg weekly for 7 doses (Doses 2 - 8), followed 5 weeks later by 1,000 mg every 4 weeks for 4 doses (Doses 9 - 12))

Participants with CLL received treatments as follows:

Cohort 3d: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + fludarabine 40 mg/m^2 orally on Days 1 - 5 of each 28-day cycle, Cycles 1 - 6

Participants with CLL received treatments as follows:

Cohort 6a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12

Participants with CLL received treatments as follows:

Cohort 6b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12

Participants with CLL and iNHL received treatments as follows:

Cohort 7a: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 5 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Cohort 7b: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 10 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Cohort 7c: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 20 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Overall Number of Participants Analyzed 40 43 8 11 27 15 11 10 14 5
Median (Inter-Quartile Range)
Unit of Measure: months
1.9
(1.9 to 2.1)
1.9
(1.9 to 2.0)
1.9
(1.9 to 2.6)
1.9
(1.9 to 1.9)
1.9
(1.9 to 2.0)
1.9
(1.9 to 2.3)
1.9
(1.8 to 1.9)
1.9
(1.9 to 1.9)
1.9
(1.9 to 3.7)
3.0
(2.6 to 4.0)
6.Secondary Outcome
Title Progression-free Survival
Hide Description

Progression free survival (PFS) was defined as the interval from the start of study drug to the earlier of the first documentation of disease progression or death from any cause.

The response definitions were based on the following standard criteria established for each indication:

  • CLL: International Workshop on chronic lymphocytic leukemia (IWCLL), 2008
  • iNHL & MCL: Cheson, 2007
Time Frame Up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the ITT analysis set were analyzed. Per prespecified analysis, participants for this outcome measure were grouped by disease and treatment regimen (cohort).
Arm/Group Title Idelalisib + Rituximab Idelalisib + Bendamustine Idelalisib + Everolimus Idelalisib + Bortezomib Idelalisib + Rituximab + Bendamustine Idelalisib + Ofatumumab Idelalisib + Fludarabine Idelalisib + Chlorambucil Idelalisib + Rituximab + Chlorambucil Idelalisib + Rituximab + Lenalidomide
Hide Arm/Group Description:

Participants with chronic CLL and iNHL received treatments as follows:

Cohort 1a: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15 & 22, Cycles 1 & 2

Cohort 2a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Cohort 3e: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Cohort 4a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle, starting Cycle 2 Day 1 with the 5th dose of rituximab + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Participants with CLL and iNHL received treatments as follows:

Cohort 1b: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 2b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3f: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3g: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 4b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle starting Cycle 2, Day 3 (after the Cycle 2 bendamustine dosing) + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Participants with MCL received treatments as follows:

Cohort 5a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + everolimus 10 mg orally once daily on Days 1 - 28 of each 28-day cycle

Participants with MCL received treatments as follows:

Cohort 5b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 8 & 15 of each 28-day cycle

Participants with CLL, iNHL and MCL received treatments as follows:

Cohort 3a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle from Cycles 1 - 6

Cohort 5c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Participants with CLL received treatments as follows:

Cohort 3c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + ofatumumab 12 doses (300 mg (Day 1 or Day 2, Dose 1), followed 1 week later by 1,000 mg weekly for 7 doses (Doses 2 - 8), followed 5 weeks later by 1,000 mg every 4 weeks for 4 doses (Doses 9 - 12))

Participants with CLL received treatments as follows:

Cohort 3d: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + fludarabine 40 mg/m^2 orally on Days 1 - 5 of each 28-day cycle, Cycles 1 - 6

Participants with CLL received treatments as follows:

Cohort 6a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12

Participants with CLL received treatments as follows:

Cohort 6b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12

Participants with CLL and iNHL received treatments as follows:

Cohort 7a: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 5 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Cohort 7b: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 10 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Cohort 7c: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 20 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Overall Number of Participants Analyzed 51 51 18 18 33 21 12 15 15 7
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
4.3
(1.6 to 11.1)
8.1 [2] 
(1.8 to NA)
NA [3] 
(11.7 to NA)
NA [3] 
(8.7 to NA)
NA [3] 
(5.4 to NA)
NA [1] 
(NA to NA)
NA [3] 
(6.7 to NA)
NA [3] 
(5.5 to NA)
[1]
NA = Not Reached; too few events to estimate the median and the lower and upper limits of the confidence interval
[2]
NA = Not Reached; too few events to estimate the upper limit of the confidence interval
[3]
NA = Not Reached; too few events to estimate the median and the upper limit of the confidence interval
7.Secondary Outcome
Title Overall Survival
Hide Description Overall Survival (OS) was defined as the interval from the start of study drug to death from any cause.
Time Frame Up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the ITT analysis set were analyzed. Per prespecified analysis, participants for this outcome measure were grouped by disease and treatment regimen (cohort).
Arm/Group Title Idelalisib + Rituximab Idelalisib + Bendamustine Idelalisib + Everolimus Idelalisib + Bortezomib Idelalisib + Rituximab + Bendamustine Idelalisib + Ofatumumab Idelalisib + Fludarabine Idelalisib + Chlorambucil Idelalisib + Rituximab + Chlorambucil Idelalisib + Rituximab + Lenalidomide
Hide Arm/Group Description:

Participants with chronic CLL and iNHL received treatments as follows:

Cohort 1a: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15 & 22, Cycles 1 & 2

Cohort 2a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Cohort 3e: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Cohort 4a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle, starting Cycle 2 Day 1 with the 5th dose of rituximab + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Participants with CLL and iNHL received treatments as follows:

Cohort 1b: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 2b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3f: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3g: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 4b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle starting Cycle 2, Day 3 (after the Cycle 2 bendamustine dosing) + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Participants with MCL received treatments as follows:

Cohort 5a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + everolimus 10 mg orally once daily on Days 1 - 28 of each 28-day cycle

Participants with MCL received treatments as follows:

Cohort 5b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 8 & 15 of each 28-day cycle

Participants with CLL, iNHL and MCL received treatments as follows:

Cohort 3a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle from Cycles 1 - 6

Cohort 5c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Participants with CLL received treatments as follows:

Cohort 3c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + ofatumumab 12 doses (300 mg (Day 1 or Day 2, Dose 1), followed 1 week later by 1,000 mg weekly for 7 doses (Doses 2 - 8), followed 5 weeks later by 1,000 mg every 4 weeks for 4 doses (Doses 9 - 12))

Participants with CLL received treatments as follows:

Cohort 3d: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + fludarabine 40 mg/m^2 orally on Days 1 - 5 of each 28-day cycle, Cycles 1 - 6

Participants with CLL received treatments as follows:

Cohort 6a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12

Participants with CLL received treatments as follows:

Cohort 6b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12

Participants with CLL and iNHL received treatments as follows:

Cohort 7a: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 5 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Cohort 7b: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 10 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Cohort 7c: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 20 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Overall Number of Participants Analyzed 51 51 18 18 33 21 12 15 15 7
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [2] 
(3.4 to NA)
NA [2] 
(5.2 to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [2] 
(6.3 to NA)
NA [1] 
(NA to NA)
NA [2] 
(6.7 to NA)
NA [2] 
(5.5 to NA)
[1]
NA = Not Reached; too few events to estimate the median and the lower and upper limits of the confidence interval
[2]
NA = Not Reached; too few events to estimate the median and the upper limit of the confidence interval
8.Secondary Outcome
Title Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5)
Hide Description [Not Specified]
Time Frame Predose, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0 hours postdose at Week 0; predose, 1.5 hours postdose at Weeks 4, 12, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic (PK) analysis set included data from participants in the ITT analysis set who had the necessary baseline and on-study measurements to provide interpretable results for the specific parameters of interest. Per prespecified analysis, data were summarized for participants in Cohort 1a 1b, who received idelalisib 100 mg and for participants in Cohorts 2a, 2b, 3a, 3b, 3c, 3d, 3e, 3f, 3g 5a, 5b, and 5c who received idelalisib 150 mg.
Arm/Group Title Idelalisib 100 mg (Cohort 1) Idelalisib 150 mg (Cohorts 2 and 3) Idelalisib 150 mg (Cohort 5)
Hide Arm/Group Description:

Participants analyzed for this group included participants from Cohort 1 (subcohort 1a and 1b) who received the treatments as follows:

Cohort 1a: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15 & 22, Cycles 1 & 2

Cohort 1b: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycle 1 - 6

Participants analyzed for this group included participants from Cohort 2a, 2b, 3a, 3b, 3c, 3e, 3f, 3g who received the treatments as follows:

Cohort 2a: IDELA 150 mg orally (po) BID, D1 - D28 of each cycle + rituximab 375 mg/m^2 IV on D1, D8, D15, & D22, C1 & C2

Cohort 2b: IDELA 150 mg po BID, D1 - D28 of each cycle + bendamustine 90 mg/m^2 IV, D1 & D2, C1 - C6

Cohorts 3a and 3b: IDELA 150 mg po BID, D1 - D28 of each cycle + rituximab 375 mg/m^2 IV on D1, C1 - C6 + bendamustine 90 mg/m^2 (Cohort 3a only) IV, D1 & D2, C1 - C6 + bendamustine 70 mg/m^2 (Cohort 3b only) IV on D1 & D2, C1 - C6

Cohort 3c: IDELA 150 mg po BID, D1 - D28 of each cycle + ofatumumab 12 doses (300 mg (D1 or D2, Dose 1), followed 1 week later by 1,000 mg weekly for 7 doses (Doses 2 - 8), followed 5 weeks later by 1,000 mg every 4 weeks for 4 doses (Doses 9 - 12))

Cohort 3d: IDELA 150 mg po BID, D1 - D28 of each cycle + fludarabine 40 mg/m^2 po D1 - D5, C1 - C6

Cohort 3e: IDELA 150 mg po BID, D1 - D28 of each cycle + rituximab 375 mg/m^2 IV on D1, D8, D15, & D22, C1 & C2

Cohorts 3f and 3g: IDELA 150 mg po BID, D1 - D28 of each cycle + bendamustine 90 mg/m^2 (cohort 3f only) IV, D1 & D2, C1 - C6 + bendamustine 70 mg/m^2 (Cohort 3g only) IV, D1 & D2, C1 - C6

C= Cycle D= Day Cycle length= 28 days

Participants analyzed for this group included participants from Cohort 5 (subcohorts 5a, 5b, and 5c) who received the treatments as follows:

Cohort 5a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + everolimus 10 mg orally once daily on Days 1 - 28 of each 28-day cycle

Cohort 5b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 8 & 15 of each 28-day cycle

Cohort 5c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Overall Number of Participants Analyzed 24 123 45
Mean (Standard Deviation)
Unit of Measure: ng/mL
Pre-dose (Week 0) Number Analyzed 24 participants 111 participants 36 participants
0.4  (2.16) 68.8  (396.94) 0.0  (0.0)
0.5 hr post-dose (Week 0) Number Analyzed 7 participants 22 participants 1 participants
437.6  (380.08) 1231.4  (1238.20) 1380.0
1.0 hr post-dose (Week 0) Number Analyzed 7 participants 22 participants 1 participants
1022.4  (652.92) 1789.3  (1162.31) 1600.0
1.5 hr post-dose (Week 0) Number Analyzed 24 participants 112 participants 36 participants
1434.0  (835.25) 2017.3  (1241.96) 1564.7  (983.46)
2.0 hr post-dose (Week 0) Number Analyzed 7 participants 21 participants 1 participants
1282.7  (789.24) 1732.8  (744.87) 1400.0
3.0 hr post-dose (Week 0) Number Analyzed 7 participants 22 participants 1 participants
1001.0  (633.99) 1296.1  (509.80) 1170.0
4.0 hr post-dose (Week 0) Number Analyzed 7 participants 22 participants 1 participants
788.4  (629.67) 910.0  (420.79) 795.0
6.0 hr post-dose (Week 0) Number Analyzed 7 participants 21 participants 1 participants
523.7  (418.80) 486.0  (276.75) 517.0
Pre-dose (Week 4) Number Analyzed 22 participants 99 participants 29 participants
416.5  (636.01) 364.1  (341.84) 408.0  (699.35)
1.5 hr post-dose (Week 4) Number Analyzed 20 participants 95 participants 24 participants
1297.2  (681.43) 1808.1  (931.67) 1877.9  (859.74)
Pre-dose (Week 12) Number Analyzed 19 participants 78 participants 16 participants
361.9  (580.70) 351.4  (389.78) 433.9  (529.79)
1.5 hr post-dose (Week 12) Number Analyzed 17 participants 77 participants 12 participants
1309.5  (750.50) 1883.0  (973.26) 1426.8  (917.02)
Pre-dose (Week 24) Number Analyzed 11 participants 76 participants 7 participants
369.9  (461.67) 419.7  (359.03) 549.1  (622.95)
1.5 hr post-dose (Week 24) Number Analyzed 8 participants 72 participants 5 participants
1061.6  (567.90) 1840.1  (1035.91) 885.6  (568.81)
9.Secondary Outcome
Title Plasma Concentration of IDELA (Cohort 4)
Hide Description [Not Specified]
Time Frame Predose at Week 0; predose, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0 hours postdose at Week 4; predose, 1.5 hours postdose at Week 12; and predose, 1.5 hours postdose at Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PK analysis set with available data were analyzed. Per prespecified analysis, data were summarized for participants in Cohort 4a, 4b who received idelalisib 150mg.
Arm/Group Title Idelalisib 150 mg (Cohort 4)
Hide Arm/Group Description:

Participants analyzed for this group included participants from Cohort 4 (subcohorts 4a and 4b) who received the treatments as follows:

Cohort 4a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle, starting Cycle 2 Day 1 with the 5th dose of rituximab + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Cohort 4b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle starting Cycle 2, Day 3 (after the Cycle 2 bendamustine dosing) + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Overall Number of Participants Analyzed 18
Mean (Standard Deviation)
Unit of Measure: ng/mL
Pre-dose (Week 0) Number Analyzed 3 participants
0.0  (0.0)
Pre-dose (Week 4) Number Analyzed 13 participants
0.0  (0.0)
0.5 hr post-dose (Week 4) Number Analyzed 2 participants
1119.5  (1513.99)
1.0 hr post-dose (Week 4) Number Analyzed 2 participants
994.5  (601.75)
1.5 hr post-dose (Week 4) Number Analyzed 12 participants
1758.2  (1414.07)
2.0 hr post-dose (Week 4) Number Analyzed 2 participants
737.0  (108.89)
3.0 hr post-dose (Week 4) Number Analyzed 2 participants
605.0  (18.38)
4.0 hr post-dose (Week 4) Number Analyzed 2 participants
547.0  (158.39)
6.0 hr post-dose (Week 4) Number Analyzed 2 participants
524.0  (404.47)
Pre-dose (Week 12) Number Analyzed 13 participants
401.9  (344.93)
1.5 hr post-dose (Week 12) Number Analyzed 11 participants
2018.2  (1703.98)
Pre-dose (Week 24) Number Analyzed 12 participants
752.5  (967.91)
1.5 hr post-dose (Week 24) Number Analyzed 10 participants
2251.1  (1744.44)
10.Secondary Outcome
Title Plasma Concentration of IDELA (Cohort 6)
Hide Description [Not Specified]
Time Frame Predose, 1.5 hours postdose at Weeks 0, 4, 12 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PK analysis set with available data were analyzed. Per prespecified analysis, data were summarized for participants in Cohort 6a, 6b who received idelalisib 150mg.
Arm/Group Title Idelalisib 150 mg (Cohort 6)
Hide Arm/Group Description:

Participants analyzed for this group included participants from Cohort 6 (subcohorts 6a and 6b) who received the treatments as follows

Cohort 6a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12

Cohort 6b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12

Overall Number of Participants Analyzed 30
Mean (Standard Deviation)
Unit of Measure: ng/mL
Pre-dose (Week 0) Number Analyzed 30 participants
0.0  (0.0)
1.5 hr post-dose (Week 0) Number Analyzed 27 participants
1930.7  (1220.87)
Pre-dose (Week 4) Number Analyzed 24 participants
530.8  (563.59)
1.5 hr post-dose (Week 4) Number Analyzed 22 participants
1869.8  (1001.39)
Pre-dose (Week 12) Number Analyzed 25 participants
677.9  (940.94)
1.5 hr post-dose (Week 12) Number Analyzed 18 participants
1733.0  (941.94)
Pre-dose (Week 24) Number Analyzed 21 participants
346.8  (377.84)
1.5 hr post-dose (Week 24) Number Analyzed 19 participants
1710.7  (1235.08)
11.Secondary Outcome
Title Plasma Concentration of IDELA (Cohort 7)
Hide Description [Not Specified]
Time Frame Predose, 1.5 hours postdose at Weeks 0, 5 and 13
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PK analysis set with available data were analyzed. Per prespecified analysis, data were summarized for participants in Cohort 7a, 7b, 7c who received idelalisib 150mg.
Arm/Group Title Idelalisib 150 mg (Cohort 7)
Hide Arm/Group Description:

Participants analyzed for this group included participants from Cohort 7 (subcohorts 7a, 7b, and 7c) who received the treatments as follows:

Cohort 7a: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 5 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Cohort 7b: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 10 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Cohort 7c: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 20 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Overall Number of Participants Analyzed 7
Mean (Standard Deviation)
Unit of Measure: ng/mL
Pre-dose (Week 0) Number Analyzed 7 participants
NA [1]   (NA)
1.5 hr post-dose (Week 0) Number Analyzed 7 participants
1603.1  (1196.78)
Pre-dose (Week 5) Number Analyzed 6 participants
20.7  (50.13)
1.5 hr post-dose (Week 5) Number Analyzed 6 participants
1621.3  (663.80)
Pre-dose (Week 13) Number Analyzed 4 participants
354.8  (278.62)
1.5 hr post-dose (Week 13) Number Analyzed 3 participants
592.7  (597.52)
[1]
Values were below the limit of quantitation
12.Secondary Outcome
Title Sub-study: Plasma Concentration of IDELA (Cohorts 1-4)
Hide Description [Not Specified]
Time Frame pre dose and 0.5, 1, 1.5, 2.0, 3.0, 4.0, and 6.0 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with CLL or iNHL from the PK Analysis Set in Cohorts 1, 2, 3, and 4 who participated in the PK substudy were analyzed. Per prespecified analysis, data were summarized for participants in Cohort 1a, 1b who received idelalisib 100mg and Cohorts 2a, 2b, 3a, 3c, 3d, 3e, 3f, 3g, 4a, 4b who received idelalisib 150 mg in the PK substudy.
Arm/Group Title Idelalisib 100 mg (Cohort 1a, 1b) Idelalisib 150 mg (Cohorts 2a, 2b, 3a, 3c, 3d, 3e, 3f, 3g, 4a, 4b)
Hide Arm/Group Description:

Participants analyzed for this group included participants from Cohort 1 who received the treatments as follows:

Cohort 1a: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15 & 22, Cycles 1 & 2

Cohort 1b: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Participants included for analysis received treatments as follows:

Cohort 2a: IDELA 150 mg po BID, D1 - D28 of each cycle + rituximab 375 mg/m^2 IV on D1, D8, D15, & D22, C1 & C2

Cohort 2b: IDELA 150 mg po BID, D1 - D28 of each cycle + bendamustine 90 mg/m^2 IV, D1 & D2, C1 - C6

Cohorts 3a and 3b: IDELA 150 mg po BID, D1 - D28 of each cycle + rituximab 375 mg/m^2 IV on D1, C1 - C6 + bendamustine 90 mg/m^2 (Cohort 3a only) IV, D1 & D2, C1 - C6 + bendamustine 70 mg/m^2 (Cohort 3b only) IV on D1 & D2, C1 - C6

Cohort 3c: IDELA 150 mg po BID, D1 - D28 of each cycle + ofatumumab 12 doses (300 mg (D1 or D2, Dose 1), followed 1 week later by 1,000 mg weekly for 7 doses (Doses 2 - 8), followed 5 weeks later by 1,000 mg every 4 weeks for 4 doses (Doses 9 - 12))

Cohort 3d: IDELA 150 mg po BID, D1 - D28 of each cycle + fludarabine 40 mg/m^2 po D1 - D5, C1 - C6

Cohort 3e: IDELA 150 mg po BID, D1 - D28 of each cycle + rituximab 375 mg/m^2 IV on D1, D8, D15, & D22, C1 & C2

Cohorts 3f and 3g: IDELA 150 mg po BID, D1 - D28 of each cycle + bendamustine 90 mg/m^2 (Cohort 3f only) IV, D1 & D2, C1 - C6 + bendamustine 70 mg/m^2 (Cohort 3g only) IV, D1 & D2, C1 - C6

Cohort 4a: IDELA 150 mg po BID, D1 - D28 of each cycle (starting C2 D1) + rituximab 375 mg/m^2 IV, D1, D8, D15, & D22, C1 & C2

Cohort 4b: IDELA 150 mg po BID, D1 - D28 of each cycle (starting C2, D3) + bendamustine 90 mg/m^2 IV, D1 & D2, C1 - C6

C= Cycle D= Day Cycle length= 28 days

Overall Number of Participants Analyzed 7 24
Mean (Standard Deviation)
Unit of Measure: ng/mL
Pre-dose Number Analyzed 7 participants 24 participants
1.5  (4.01) 0.0  (0.0)
0.5 hr post-dose Number Analyzed 7 participants 24 participants
437.6  (380.08) 1222.1  (1224.95)
1.0 hr post-dose Number Analyzed 7 participants 24 participants
1022.4  (652.92) 1723.1  (1140.00)
1.5 hr post-dose Number Analyzed 7 participants 24 participants
1264.7  (868.41) 1599.2  (746.58)
2.0 hr post-dose Number Analyzed 7 participants 23 participants
1282.7  (789.24) 1646.2  (766.31)
3.0 hr post-dose Number Analyzed 7 participants 24 participants
1001.0  (633.99) 1238.5  (524.77)
4.0 hr post-dose Number Analyzed 7 participants 24 participants
788.4  (629.67) 879.8  (416.25)
6.0 hr post-dose Number Analyzed 7 participants 23 participants
523.7  (418.80) 489.3  (277.82)
13.Secondary Outcome
Title Plasma Concentration of Bendamustine
Hide Description [Not Specified]
Time Frame Predose, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0 hours postdose at Week 0
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PK analysis set with available data were analyzed. Per prespecified analysis, data were summarized for participants in Cohorts 1b, 2b, 3a, 3b, 3f, 3g, 4b, 5c who received bendamustine.
Arm/Group Title Bendamustine (Cohorts 1b, 2b, 3a, 3b, 3f, 3g, 4b, 5c)
Hide Arm/Group Description:

Participants included for analysis received treatments as follows:

Cohort 1b: IDELA 100 mg po BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 2b: IDELA 150 mg po BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3a: IDELA 150 mg po BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3b: IDELA 150 mg po BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle from Cycles 1 - 6

Cohort 3f: IDELA 150 mg po BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3g: IDELA 150 mg po BID on Days 1 - 28 of each 28-day cycle + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 4b: IDELA 150 mg po BID on Days 1 - 28 of each 28-day cycle starting Cycle 2, Day 3 (after the Cycle 2 bendamustine dosing) + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 5c: IDELA 150 mg po BID on Days 1 - 28 + rituximab 375 mg/m^2 IV on Day 1, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2, Cycles 1 - 6 (Cycle length= 28 days)

Overall Number of Participants Analyzed 19
Mean (Standard Deviation)
Unit of Measure: ng/mL
Pre-dose (Week 0) Number Analyzed 19 participants
NA [1]   (NA)
0.25 hr post-dose (Week 0) Number Analyzed 18 participants
3484.1  (2617.17)
0.5 hr post-dose (Week 0) Number Analyzed 18 participants
4694.7  (3570.78)
0.75 hr post-dose (Week 0) Number Analyzed 19 participants
3433.2  (2991.15)
1.0 hr post-dose (Week 0) Number Analyzed 18 participants
2847.2  (2462.90)
1.25 hr post-dose (Week 0) Number Analyzed 18 participants
1916.4  (1551.50)
1.5 hr post-dose (Week 0) Number Analyzed 17 participants
1211.2  (1093.74)
2.0 hr post-dose (Week 0) Number Analyzed 18 participants
514.0  (489.76)
3.0 hr post-dose (Week 0) Number Analyzed 18 participants
463.4  (1529.30)
4.0 hr post-dose (Week 0) Number Analyzed 18 participants
78.5  (238.30)
5.0 hr post-dose (Week 0) Number Analyzed 18 participants
15.3  (36.79)
6.0 hr post-dose (Week 0) Number Analyzed 16 participants
4.4  (6.58)
[1]
Values were below the limit of quantitation
14.Secondary Outcome
Title Plasma Concentration of Everolimus
Hide Description [Not Specified]
Time Frame Predose, 1.5 hours postdose at Weeks 0 and 4
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PK analysis set with available data were analyzed. Data were summarized for participants in Cohort 5a who received everolimus.
Arm/Group Title Everolimus (Cohort 5a)
Hide Arm/Group Description:

Participants analyzed for this group included participants from Cohort 5 (subcohort 5a) who received the treatments as follows:

Cohort 5a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + everolimus 10 mg orally once daily on Days 1 - 28 of each 28-day cycle

Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: ng/mL
Pre-dose (Week 0) Number Analyzed 4 participants
NA [1]   (NA)
1.5 hr post-dose (Week 0) Number Analyzed 6 participants
93.0  (63.50)
Pre-dose (Week 4) Number Analyzed 2 participants
3.0  (3.79)
1.5 hr post-dose (Week 4) Number Analyzed 2 participants
56.3  (67.48)
[1]
Values were below the limit of quantitation
15.Secondary Outcome
Title Plasma Concentration of Lenalidomide
Hide Description [Not Specified]
Time Frame Predose, 1.5 hours postdose at Week 1 and predose at Week 5
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PK analysis set with available data were analyzed. Per prespecified analysis, data were summarized for participants in Cohort 7a, 7b, 7c who received lenalidomide.
Arm/Group Title Lenalidomide (Cohort 7a, 7b, 7c)
Hide Arm/Group Description:

Participants analyzed for this group included participants from Cohort 7 (subcohorts 7a, 7b, and 7c) who received the treatments as follows:

Cohort 7a: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 5 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Cohort 7b: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 10 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Cohort 7c: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 20 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Overall Number of Participants Analyzed 7
Mean (Standard Deviation)
Unit of Measure: ng/mL
Pre-dose (Week 1) Number Analyzed 7 participants
NA [1]   (NA)
1.5 hr post-dose (Week 1) Number Analyzed 6 participants
51.6  (31.77)
Pre-dose (Week 5) Number Analyzed 2 participants
NA [1]   (NA)
[1]
Values were below the limit of quantitation
Time Frame First dose date up to 5 years
Adverse Event Reporting Description The ITT analysis set included participants who received at least 1 dose of study drug (IDELA or combination drugs). Per prespecified analysis, participants were grouped by disease (CLL, iNHL, MCL) and by treatment regimen (cohort).
 
Arm/Group Title Idelalisib + Rituximab Idelalisib + Bendamustine Idelalisib + Everolimus Idelalisib + Bortezomib Idelalisib + Rituximab + Bendamustine Idelalisib + Ofatumumab Idelalisib + Fludarabine Idelalisib + Chlorambucil Idelalisib + Rituximab + Chlorambucil Idelalisib + Rituximab + Lenalidomide
Hide Arm/Group Description

Participants with chronic CLL and iNHL received treatments as follows:

Cohort 1a: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15 & 22, Cycles 1 & 2

Cohort 2a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Cohort 3e: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Cohort 4a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle, starting Cycle 2 Day 1 with the 5th dose of rituximab + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Participants with CLL and iNHL received treatments as follows:

Cohort 1b: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 2b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3f: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3g: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 4b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle starting Cycle 2, Day 3 (after the Cycle 2 bendamustine dosing) + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Participants with MCL received treatments as follows:

Cohort 5a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + everolimus 10 mg orally once daily on Days 1 - 28 of each 28-day cycle

Participants with MCL received treatments as follows:

Cohort 5b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 8 & 15 of each 28-day cycle

Participants with CLL, iNHL and MCL received treatments as follows:

Cohort 3a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Cohort 3b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle from Cycles 1 - 6

Cohort 5c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Participants with CLL received treatments as follows:

Cohort 3c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + ofatumumab 12 doses (300 mg (Day 1 or Day 2, Dose 1), followed 1 week later by 1,000 mg weekly for 7 doses (Doses 2 - 8), followed 5 weeks later by 1,000 mg every 4 weeks for 4 doses (Doses 9 - 12))

Participants with CLL received treatments as follows:

Cohort 3d: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + fludarabine 40 mg/m^2 orally on Days 1 - 5 of each 28-day cycle, Cycles 1 - 6

Participants with CLL received treatments as follows:

Cohort 6a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12

Participants with CLL received treatments as follows:

Cohort 6b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12

Participants with CLL and iNHL received treatments as follows:

Cohort 7a: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 5 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Cohort 7b: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 10 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

Cohort 7c: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 20 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles

All-Cause Mortality
Idelalisib + Rituximab Idelalisib + Bendamustine Idelalisib + Everolimus Idelalisib + Bortezomib Idelalisib + Rituximab + Bendamustine Idelalisib + Ofatumumab Idelalisib + Fludarabine Idelalisib + Chlorambucil Idelalisib + Rituximab + Chlorambucil Idelalisib + Rituximab + Lenalidomide
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/51 (1.96%)   6/51 (11.76%)   4/18 (22.22%)   3/18 (16.67%)   1/33 (3.03%)   4/21 (19.05%)   2/12 (16.67%)   0/15 (0.00%)   3/15 (20.00%)   2/7 (28.57%) 
Hide Serious Adverse Events
Idelalisib + Rituximab Idelalisib + Bendamustine Idelalisib + Everolimus Idelalisib + Bortezomib Idelalisib + Rituximab + Bendamustine Idelalisib + Ofatumumab Idelalisib + Fludarabine Idelalisib + Chlorambucil Idelalisib + Rituximab + Chlorambucil Idelalisib + Rituximab + Lenalidomide
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   20/51 (39.22%)   37/51 (72.55%)   14/18 (77.78%)   6/18 (33.33%)   17/33 (51.52%)   12/21 (57.14%)   9/12 (75.00%)   9/15 (60.00%)   8/15 (53.33%)   5/7 (71.43%) 
Blood and lymphatic system disorders                     
Anaemia  1  0/51 (0.00%)  2/51 (3.92%)  1/18 (5.56%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Autoimmune haemolytic anaemia  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Coombs positive haemolytic anaemia  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/7 (0.00%) 
Febrile neutropenia  1  3/51 (5.88%)  5/51 (9.80%)  2/18 (11.11%)  0/18 (0.00%)  1/33 (3.03%)  1/21 (4.76%)  1/12 (8.33%)  4/15 (26.67%)  2/15 (13.33%)  0/7 (0.00%) 
Immune thrombocytopenic purpura  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Neutropenia  1  0/51 (0.00%)  2/51 (3.92%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Pancytopenia  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Thrombocytopenia  1  1/51 (1.96%)  2/51 (3.92%)  1/18 (5.56%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  1/7 (14.29%) 
Cardiac disorders                     
Atrial fibrillation  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  2/33 (6.06%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Cardiac arrest  1  1/51 (1.96%)  0/51 (0.00%)  0/18 (0.00%)  1/18 (5.56%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Cardiac failure  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Supraventricular tachycardia  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Endocrine disorders                     
Endocrine disorder  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  1/21 (4.76%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Eye disorders                     
Retinal detachment  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Uveitis  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Gastrointestinal disorders                     
Abdominal pain  1  2/51 (3.92%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Colitis  1  2/51 (3.92%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  1/21 (4.76%)  0/12 (0.00%)  2/15 (13.33%)  1/15 (6.67%)  1/7 (14.29%) 
Colitis ischaemic  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Colitis microscopic  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  1/18 (5.56%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Diarrhoea  1  2/51 (3.92%)  2/51 (3.92%)  0/18 (0.00%)  1/18 (5.56%)  2/33 (6.06%)  1/21 (4.76%)  0/12 (0.00%)  1/15 (6.67%)  2/15 (13.33%)  0/7 (0.00%) 
Dysphagia  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Gastrointestinal haemorrhage  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  1/21 (4.76%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Gingival bleeding  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Intestinal obstruction  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Large intestinal ulcer  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Mouth haemorrhage  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Nausea  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Neutropenic colitis  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Peptic ulcer  1  1/51 (1.96%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Rectal haemorrhage  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Stomatitis  1  0/51 (0.00%)  0/51 (0.00%)  1/18 (5.56%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Vomiting  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
General disorders                     
Asthenia  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Chest pain  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Fatigue  1  0/51 (0.00%)  2/51 (3.92%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Generalised oedema  1  1/51 (1.96%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Mucosal inflammation  1  0/51 (0.00%)  0/51 (0.00%)  1/18 (5.56%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Multi-organ failure  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  1/21 (4.76%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Pyrexia  1  1/51 (1.96%)  10/51 (19.61%)  1/18 (5.56%)  1/18 (5.56%)  5/33 (15.15%)  2/21 (9.52%)  1/12 (8.33%)  1/15 (6.67%)  0/15 (0.00%)  2/7 (28.57%) 
Hepatobiliary disorders                     
Cholecystitis  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Cholecystitis acute  1  1/51 (1.96%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Cholecystitis chronic  1  1/51 (1.96%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Hepatic failure  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/7 (14.29%) 
Hepatitis  1  1/51 (1.96%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Immune system disorders                     
Hypersensitivity  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Infections and infestations                     
Aspergillus infection  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  2/15 (13.33%)  0/7 (0.00%) 
Atypical pneumonia  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Bacteraemia  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Bacterial infection  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  1/21 (4.76%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Bronchiolitis  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  1/18 (5.56%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Bronchitis  1  1/51 (1.96%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  1/21 (4.76%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Bronchopulmonary aspergillosis  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Candida infection  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  1/21 (4.76%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Cellulitis  1  1/51 (1.96%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Clostridium difficile colitis  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Clostridium difficile infection  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Cytomegalovirus gastrointestinal infection  1  1/51 (1.96%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Cytomegalovirus infection  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Cytomegalovirus viraemia  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/7 (0.00%) 
Diverticulitis  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Encephalitis  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Enterococcal bacteraemia  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Escherichia bacteraemia  1  0/51 (0.00%)  2/51 (3.92%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Escherichia sepsis  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Folliculitis  1  0/51 (0.00%)  0/51 (0.00%)  1/18 (5.56%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Gastroenteritis  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Gastroenteritis salmonella  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/7 (0.00%) 
Groin abscess  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Herpes zoster  1  1/51 (1.96%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Herpes zoster disseminated  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Herpes zoster pharyngitis  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Human herpesvirus 6 infection  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  2/12 (16.67%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Listeria sepsis  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Listeriosis  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Lung infection  1  0/51 (0.00%)  0/51 (0.00%)  1/18 (5.56%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Mycobacterium avium complex infection  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Neutropenic sepsis  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  1/21 (4.76%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Ophthalmic herpes zoster  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Perirectal abscess  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Pneumocystis jirovecii pneumonia  1  0/51 (0.00%)  2/51 (3.92%)  1/18 (5.56%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  1/12 (8.33%)  2/15 (13.33%)  1/15 (6.67%)  0/7 (0.00%) 
Pneumonia  1  4/51 (7.84%)  10/51 (19.61%)  2/18 (11.11%)  0/18 (0.00%)  1/33 (3.03%)  3/21 (14.29%)  1/12 (8.33%)  1/15 (6.67%)  1/15 (6.67%)  0/7 (0.00%) 
Pneumonia bacterial  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Pneumonia fungal  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  1/7 (14.29%) 
Pneumonia haemophilus  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Pneumonia influenzal  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Pseudomonal bacteraemia  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Sepsis  1  0/51 (0.00%)  4/51 (7.84%)  0/18 (0.00%)  1/18 (5.56%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  1/15 (6.67%)  1/15 (6.67%)  0/7 (0.00%) 
Septic shock  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Staphylococcal bacteraemia  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Streptococcal bacteraemia  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Tooth infection  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Upper respiratory tract infection  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  1/21 (4.76%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Urinary tract infection  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Vaginal infection  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Viral upper respiratory tract infection  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Injury, poisoning and procedural complications                     
Fall  1  1/51 (1.96%)  0/51 (0.00%)  0/18 (0.00%)  1/18 (5.56%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Pelvic fracture  1  1/51 (1.96%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Subdural haematoma  1  1/51 (1.96%)  1/51 (1.96%)  0/18 (0.00%)  1/18 (5.56%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Investigations                     
Alanine aminotransferase increased  1  1/51 (1.96%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  2/7 (28.57%) 
Aspartate aminotransferase increased  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  2/7 (28.57%) 
Blood bilirubin increased  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/7 (14.29%) 
Blood lactate dehydrogenase increased  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  2/7 (28.57%) 
Hepatic enzyme increased  1  1/51 (1.96%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Transaminases increased  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  1/21 (4.76%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Weight decreased  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Metabolism and nutrition disorders                     
Decreased appetite  1  1/51 (1.96%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Failure to thrive  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Hypercalcaemia  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  1/18 (5.56%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Hyperglycaemia  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Hyperkalaemia  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Hyperuricaemia  1  1/51 (1.96%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Hypoglycaemia  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Hypokalaemia  1  0/51 (0.00%)  2/51 (3.92%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Hyponatraemia  1  0/51 (0.00%)  0/51 (0.00%)  1/18 (5.56%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Lactic acidosis  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Tumour lysis syndrome  1  0/51 (0.00%)  2/51 (3.92%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  2/12 (16.67%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Musculoskeletal and connective tissue disorders                     
Arthralgia  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Myalgia  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Rhabdomyolysis  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                     
Acute myeloid leukaemia  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  1/21 (4.76%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Renal cell carcinoma  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/7 (14.29%) 
Nervous system disorders                     
Cerebral ischaemia  1  1/51 (1.96%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Cerebrovascular accident  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Dizziness  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Lethargy  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Normal pressure hydrocephalus  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Syncope  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  1/21 (4.76%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Psychiatric disorders                     
Depression  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Suicidal ideation  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Renal and urinary disorders                     
Acute kidney injury  1  2/51 (3.92%)  0/51 (0.00%)  3/18 (16.67%)  1/18 (5.56%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/7 (14.29%) 
Hydronephrosis  1  0/51 (0.00%)  0/51 (0.00%)  1/18 (5.56%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Obstructive uropathy  1  0/51 (0.00%)  0/51 (0.00%)  1/18 (5.56%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Urinary tract obstruction  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Reproductive system and breast disorders                     
Pelvic pain  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Vaginal haemorrhage  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Respiratory, thoracic and mediastinal disorders                     
Acute respiratory failure  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  2/15 (13.33%)  0/7 (0.00%) 
Bronchial secretion retention  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Bronchiectasis  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Epistaxis  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Hypoxia  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Organising pneumonia  1  0/51 (0.00%)  0/51 (0.00%)  1/18 (5.56%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Pleural effusion  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  1/18 (5.56%)  0/33 (0.00%)  1/21 (4.76%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Pleuritic pain  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Pneumonitis  1  1/51 (1.96%)  2/51 (3.92%)  1/18 (5.56%)  1/18 (5.56%)  0/33 (0.00%)  1/21 (4.76%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Pulmonary embolism  1  0/51 (0.00%)  0/51 (0.00%)  1/18 (5.56%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Pulmonary haemorrhage  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Respiratory distress  1  0/51 (0.00%)  0/51 (0.00%)  1/18 (5.56%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Respiratory failure  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  1/18 (5.56%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/7 (14.29%) 
Skin and subcutaneous tissue disorders                     
Angioedema  1  0/51 (0.00%)  0/51 (0.00%)  1/18 (5.56%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Drug eruption  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Erythema multiforme  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Rash  1  1/51 (1.96%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  3/33 (9.09%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Rash erythematous  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Rash maculo-papular  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Skin ulcer  1  0/51 (0.00%)  0/51 (0.00%)  1/18 (5.56%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Vascular disorders                     
Deep vein thrombosis  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Haemorrhage  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Hypotension  1  0/51 (0.00%)  0/51 (0.00%)  1/18 (5.56%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/7 (0.00%) 
Orthostatic hypotension  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
1
Term from vocabulary, MedDRA 18.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Idelalisib + Rituximab Idelalisib + Bendamustine Idelalisib + Everolimus Idelalisib + Bortezomib Idelalisib + Rituximab + Bendamustine Idelalisib + Ofatumumab Idelalisib + Fludarabine Idelalisib + Chlorambucil Idelalisib + Rituximab + Chlorambucil Idelalisib + Rituximab + Lenalidomide
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   51/51 (100.00%)   51/51 (100.00%)   18/18 (100.00%)   15/18 (83.33%)   33/33 (100.00%)   21/21 (100.00%)   12/12 (100.00%)   15/15 (100.00%)   15/15 (100.00%)   7/7 (100.00%) 
Blood and lymphatic system disorders                     
Anaemia  1  6/51 (11.76%)  13/51 (25.49%)  5/18 (27.78%)  5/18 (27.78%)  4/33 (12.12%)  3/21 (14.29%)  3/12 (25.00%)  3/15 (20.00%)  4/15 (26.67%)  0/7 (0.00%) 
Coombs positive haemolytic anaemia  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/7 (0.00%) 
Eosinophilia  1  0/51 (0.00%)  0/51 (0.00%)  1/18 (5.56%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Febrile neutropenia  1  0/51 (0.00%)  3/51 (5.88%)  1/18 (5.56%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/7 (0.00%) 
Hypoglobulinaemia  1  1/51 (1.96%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Iron deficiency anaemia  1  1/51 (1.96%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  2/21 (9.52%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Leukopenia  1  3/51 (5.88%)  6/51 (11.76%)  2/18 (11.11%)  2/18 (11.11%)  4/33 (12.12%)  0/21 (0.00%)  0/12 (0.00%)  4/15 (26.67%)  0/15 (0.00%)  0/7 (0.00%) 
Lymphadenopathy  1  1/51 (1.96%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/7 (0.00%) 
Lymphocytosis  1  1/51 (1.96%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Lymphopenia  1  0/51 (0.00%)  2/51 (3.92%)  1/18 (5.56%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Neutropenia  1  15/51 (29.41%)  27/51 (52.94%)  7/18 (38.89%)  4/18 (22.22%)  13/33 (39.39%)  6/21 (28.57%)  6/12 (50.00%)  9/15 (60.00%)  7/15 (46.67%)  2/7 (28.57%) 
Pancytopenia  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Thrombocytopenia  1  4/51 (7.84%)  14/51 (27.45%)  11/18 (61.11%)  4/18 (22.22%)  3/33 (9.09%)  3/21 (14.29%)  1/12 (8.33%)  5/15 (33.33%)  3/15 (20.00%)  0/7 (0.00%) 
Cardiac disorders                     
Angina pectoris  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Atrial fibrillation  1  1/51 (1.96%)  1/51 (1.96%)  3/18 (16.67%)  0/18 (0.00%)  0/33 (0.00%)  1/21 (4.76%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Cardiac failure congestive  1  0/51 (0.00%)  2/51 (3.92%)  1/18 (5.56%)  1/18 (5.56%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Cardiomyopathy  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Palpitations  1  1/51 (1.96%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  3/12 (25.00%)  0/15 (0.00%)  0/15 (0.00%)  1/7 (14.29%) 
Pulseless electrical activity  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Sinus tachycardia  1  0/51 (0.00%)  3/51 (5.88%)  1/18 (5.56%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Tachycardia  1  0/51 (0.00%)  0/51 (0.00%)  1/18 (5.56%)  0/18 (0.00%)  0/33 (0.00%)  1/21 (4.76%)  0/12 (0.00%)  0/15 (0.00%)  2/15 (13.33%)  0/7 (0.00%) 
Ear and labyrinth disorders                     
Ear pain  1  2/51 (3.92%)  3/51 (5.88%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Vertigo  1  5/51 (9.80%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Eye disorders                     
Cataract  1  1/51 (1.96%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Dry eye  1  1/51 (1.96%)  0/51 (0.00%)  2/18 (11.11%)  1/18 (5.56%)  3/33 (9.09%)  1/21 (4.76%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  2/7 (28.57%) 
Eye irritation  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Eyelid thickening  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Lacrimation increased  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  3/7 (42.86%) 
Periorbital oedema  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Vision blurred  1  3/51 (5.88%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  2/12 (16.67%)  0/15 (0.00%)  0/15 (0.00%)  1/7 (14.29%) 
Visual impairment  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Vitreous floaters  1  0/51 (0.00%)  0/51 (0.00%)  1/18 (5.56%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Gastrointestinal disorders                     
Abdominal discomfort  1  1/51 (1.96%)  1/51 (1.96%)  1/18 (5.56%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Abdominal distension  1  2/51 (3.92%)  1/51 (1.96%)  2/18 (11.11%)  2/18 (11.11%)  1/33 (3.03%)  1/21 (4.76%)  0/12 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/7 (0.00%) 
Abdominal hernia  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  1/18 (5.56%)  1/33 (3.03%)  1/21 (4.76%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Abdominal pain  1  10/51 (19.61%)  6/51 (11.76%)  1/18 (5.56%)  3/18 (16.67%)  3/33 (9.09%)  2/21 (9.52%)  1/12 (8.33%)  1/15 (6.67%)  3/15 (20.00%)  1/7 (14.29%) 
Abdominal pain lower  1  0/51 (0.00%)  1/51 (1.96%)  1/18 (5.56%)  1/18 (5.56%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/7 (0.00%) 
Abdominal pain upper  1  3/51 (5.88%)  1/51 (1.96%)  1/18 (5.56%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Abdominal tenderness  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  1/18 (5.56%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Anal haemorrhage  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  1/18 (5.56%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Anal pruritus  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Aphthous stomatitis  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  1/18 (5.56%)  2/33 (6.06%)  0/21 (0.00%)  0/12 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/7 (0.00%) 
Colitis  1  1/51 (1.96%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Constipation  1  5/51 (9.80%)  11/51 (21.57%)  2/18 (11.11%)  3/18 (16.67%)  8/33 (24.24%)  4/21 (19.05%)  2/12 (16.67%)  2/15 (13.33%)  6/15 (40.00%)  6/7 (85.71%) 
Diarrhoea  1  20/51 (39.22%)  14/51 (27.45%)  9/18 (50.00%)  7/18 (38.89%)  12/33 (36.36%)  11/21 (52.38%)  6/12 (50.00%)  6/15 (40.00%)  8/15 (53.33%)  2/7 (28.57%) 
Dry mouth  1  1/51 (1.96%)  2/51 (3.92%)  1/18 (5.56%)  0/18 (0.00%)  0/33 (0.00%)  1/21 (4.76%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Dyspepsia  1  1/51 (1.96%)  9/51 (17.65%)  1/18 (5.56%)  0/18 (0.00%)  2/33 (6.06%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  2/15 (13.33%)  0/7 (0.00%) 
Dysphagia  1  3/51 (5.88%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Faeces soft  1  1/51 (1.96%)  2/51 (3.92%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Flatulence  1  3/51 (5.88%)  2/51 (3.92%)  0/18 (0.00%)  1/18 (5.56%)  0/33 (0.00%)  1/21 (4.76%)  1/12 (8.33%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Gastritis  1  1/51 (1.96%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Gastrooesophageal reflux disease  1  1/51 (1.96%)  5/51 (9.80%)  0/18 (0.00%)  0/18 (0.00%)  2/33 (6.06%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  1/15 (6.67%)  1/7 (14.29%) 
Gingival bleeding  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/7 (0.00%) 
Gingival pain  1  1/51 (1.96%)  0/51 (0.00%)  1/18 (5.56%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Glossitis  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/7 (0.00%) 
Glossodynia  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  2/21 (9.52%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Haematochezia  1  0/51 (0.00%)  0/51 (0.00%)  1/18 (5.56%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  2/12 (16.67%)  0/15 (0.00%)  0/15 (0.00%)  1/7 (14.29%) 
Large intestine polyp  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Lip blister  1  0/51 (0.00%)  0/51 (0.00%)  1/18 (5.56%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Mouth ulceration  1  1/51 (1.96%)  1/51 (1.96%)  1/18 (5.56%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  2/12 (16.67%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Nausea  1  17/51 (33.33%)  19/51 (37.25%)  2/18 (11.11%)  3/18 (16.67%)  14/33 (42.42%)  6/21 (28.57%)  4/12 (33.33%)  4/15 (26.67%)  6/15 (40.00%)  4/7 (57.14%) 
Noninfective gingivitis  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Oesophagitis  1  1/51 (1.96%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  1/21 (4.76%)  0/12 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/7 (0.00%) 
Oral dysaesthesia  1  1/51 (1.96%)  0/51 (0.00%)  1/18 (5.56%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Oral pain  1  1/51 (1.96%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  2/33 (6.06%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Proctitis  1  0/51 (0.00%)  0/51 (0.00%)  1/18 (5.56%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Retching  1  2/51 (3.92%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Stomatitis  1  4/51 (7.84%)  4/51 (7.84%)  2/18 (11.11%)  1/18 (5.56%)  2/33 (6.06%)  1/21 (4.76%)  0/12 (0.00%)  2/15 (13.33%)  0/15 (0.00%)  2/7 (28.57%) 
Toothache  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  2/15 (13.33%)  0/15 (0.00%)  0/7 (0.00%) 
Vomiting  1  5/51 (9.80%)  6/51 (11.76%)  2/18 (11.11%)  1/18 (5.56%)  6/33 (18.18%)  3/21 (14.29%)  3/12 (25.00%)  4/15 (26.67%)  1/15 (6.67%)  2/7 (28.57%) 
General disorders                     
Asthenia  1  5/51 (9.80%)  4/51 (7.84%)  3/18 (16.67%)  2/18 (11.11%)  2/33 (6.06%)  1/21 (4.76%)  2/12 (16.67%)  0/15 (0.00%)  2/15 (13.33%)  0/7 (0.00%) 
Catheter site pain  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Chest discomfort  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  1/15 (6.67%)  2/15 (13.33%)  0/7 (0.00%) 
Chest pain  1  1/51 (1.96%)  1/51 (1.96%)  1/18 (5.56%)  1/18 (5.56%)  1/33 (3.03%)  1/21 (4.76%)  1/12 (8.33%)  1/15 (6.67%)  1/15 (6.67%)  0/7 (0.00%) 
Chills  1  8/51 (15.69%)  11/51 (21.57%)  4/18 (22.22%)  2/18 (11.11%)  4/33 (12.12%)  3/21 (14.29%)  0/12 (0.00%)  6/15 (40.00%)  1/15 (6.67%)  1/7 (14.29%) 
Face oedema  1  0/51 (0.00%)  1/51 (1.96%)  1/18 (5.56%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Fatigue  1  18/51 (35.29%)  24/51 (47.06%)  5/18 (27.78%)  4/18 (22.22%)  12/33 (36.36%)  4/21 (19.05%)  5/12 (41.67%)  4/15 (26.67%)  5/15 (33.33%)  4/7 (57.14%) 
Gait disturbance  1  1/51 (1.96%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Inflammation  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  1/18 (5.56%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Influenza like illness  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  1/18 (5.56%)  0/33 (0.00%)  1/21 (4.76%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Infusion site pain  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  3/33 (9.09%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Injection site discomfort  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  1/18 (5.56%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Injection site erythema  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  1/18 (5.56%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Injection site reaction  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  1/18 (5.56%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Malaise  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  1/21 (4.76%)  0/12 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/7 (0.00%) 
Mucosal inflammation  1  2/51 (3.92%)  3/51 (5.88%)  3/18 (16.67%)  0/18 (0.00%)  2/33 (6.06%)  1/21 (4.76%)  2/12 (16.67%)  0/15 (0.00%)  1/15 (6.67%)  1/7 (14.29%) 
Oedema  1  1/51 (1.96%)  2/51 (3.92%)  2/18 (11.11%)  0/18 (0.00%)  2/33 (6.06%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Oedema peripheral  1  4/51 (7.84%)  4/51 (7.84%)  3/18 (16.67%)  3/18 (16.67%)  4/33 (12.12%)  3/21 (14.29%)  2/12 (16.67%)  3/15 (20.00%)  2/15 (13.33%)  1/7 (14.29%) 
Pain  1  5/51 (9.80%)  4/51 (7.84%)  3/18 (16.67%)  2/18 (11.11%)  3/33 (9.09%)  0/21 (0.00%)  2/12 (16.67%)  3/15 (20.00%)  2/15 (13.33%)  0/7 (0.00%) 
Peripheral swelling  1  1/51 (1.96%)  0/51 (0.00%)  1/18 (5.56%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Pyrexia  1  18/51 (35.29%)  26/51 (50.98%)  4/18 (22.22%)  3/18 (16.67%)  18/33 (54.55%)  6/21 (28.57%)  4/12 (33.33%)  3/15 (20.00%)  8/15 (53.33%)  1/7 (14.29%) 
Hepatobiliary disorders                     
Cholecystitis acute  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/7 (0.00%) 
Immune system disorders                     
Anaphylactic reaction  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Drug hypersensitivity  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Hypersensitivity  1  2/51 (3.92%)  1/51 (1.96%)  1/18 (5.56%)  1/18 (5.56%)  0/33 (0.00%)  1/21 (4.76%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  1/7 (14.29%) 
Hypogammaglobulinaemia  1  1/51 (1.96%)  0/51 (0.00%)  1/18 (5.56%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  2/15 (13.33%)  0/7 (0.00%) 
Seasonal allergy  1  2/51 (3.92%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  1/33 (3.03%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Infections and infestations                     
Aspergillus infection  1  0/51 (0.00%)  1/51 (1.96%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Bacteraemia  1  0/51 (0.00%)  0/51 (0.00%)  1/18 (5.56%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/7 (0.00%) 
Bronchitis  1  3/51 (5.88%)  2/51 (3.92%)  0/18 (0.00%)  1/18 (5.56%)  1/33 (3.03%)  0/21 (0.00%)  0/12 (0.00%)  1/15 (6.67%)  1/15 (6.67%)  0/7 (0.00%) 
Campylobacter infection  1  0/51 (0.00%)  0/51 (0.00%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/7 (0.00%) 
Candida infection  1  1/51 (1.96%)  3/51 (5.88%)  0/18 (0.00%)  0/18 (0.00%)  0/33 (0.00%)  0/21 (0.00%)  1/12 (8.33%)  0/15 (0.00%)