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Ibrutinib With Rituximab in Adults With Waldenström's Macroglobulinemia

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ClinicalTrials.gov Identifier: NCT02165397
Recruitment Status : Completed
First Posted : June 17, 2014
Results First Posted : November 16, 2020
Last Update Posted : March 3, 2021
Sponsor:
Collaborator:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Pharmacyclics LLC.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Waldenström's Macroglobulinemia
Interventions Drug: Ibrutinib
Drug: Placebo
Drug: Rituximab
Enrollment 181
Recruitment Details This study was conducted in 48 sites (10 in the United States, 30 in Europe, 4 in Canada and 4 in Australia).
Pre-assignment Details Participants were randomized in a 1:1 ratio to receive ibrutinib + rituximab (Ibr+R) or placebo + rituximab (Pbo+R). Separately, participants refractory to treatment with rituximab were enrolled in an open-label ibrutinib monotherapy substudy to further investigate the safety and efficacy of ibrutinib.
Arm/Group Title Ibrutinib + Rituximab Placebo + Rituximab Open-Label Substudy: Ibrutinib
Hide Arm/Group Description

Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment.

Rituximab: 375 mg/m^2 intravenous (IV) per package insert weekly for four consecutive weeks (Day 1 of Weeks 1-4), followed by a second four-weekly rituximab course after a three-month interval (Weeks 17-20) for a total of 8 infusions of rituximab.

Placebo: 3 capsules of placebo orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment.

Rituximab: 375 mg/m^2 IV per package insert weekly for four consecutive weeks (Day 1 of Weeks 1-4), followed by a second four-weekly rituximab course after a three-month interval (Weeks 17-20) for a total of 8 infusions of rituximab.

Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment. Participants (rituximab refractory) were treated in an open-label substudy independently of the 2 randomized main treatment arms.
Period Title: Overall Study
Started 75 75 31
Completed [1] 61 56 21
Not Completed 14 19 10
Reason Not Completed
Death             7             10             8
Lost to Follow-up             1             3             0
Withdrawal by Subject             6             6             1
Other, Not Specified             0             0             1
[1]
On-study until study termination by sponsor.
Arm/Group Title Ibrutinib + Rituximab Placebo + Rituximab Open-Label Substudy: Ibrutinib Total
Hide Arm/Group Description

Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment.

Rituximab: 375 mg/m^2 IV per package insert weekly for four consecutive weeks (Day 1 of Weeks 1-4), followed by a second four-weekly rituximab course after a three-month interval (Weeks 17-20) for a total of 8 infusions of rituximab.

Placebo: 3 capsules of placebo orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment.

Rituximab: 375 mg/m^2 IV per package insert weekly for four consecutive weeks (Day 1 of Weeks 1-4), followed by a second four-weekly rituximab course after a three-month interval (Weeks 17-20) for a total of 8 infusions of rituximab.

Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment. Participants (rituximab refractory) were treated in an open-label substudy independently of the 2 randomized main treatment arms. Total of all reporting groups
Overall Number of Baseline Participants 75 75 31 181
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 75 participants 75 participants 31 participants 181 participants
< 65 years old
28
  37.3%
30
  40.0%
14
  45.2%
72
  39.8%
>= 65 years old
47
  62.7%
45
  60.0%
17
  54.8%
109
  60.2%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 75 participants 75 participants 31 participants 181 participants
Female
30
  40.0%
21
  28.0%
11
  35.5%
62
  34.3%
Male
45
  60.0%
54
  72.0%
20
  64.5%
119
  65.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 75 participants 75 participants 31 participants 181 participants
Hispanic or Latino
3
   4.0%
1
   1.3%
1
   3.2%
5
   2.8%
Not Hispanic or Latino
72
  96.0%
74
  98.7%
30
  96.8%
176
  97.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 75 participants 75 participants 31 participants 181 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
3
   4.0%
0
   0.0%
2
   6.5%
5
   2.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   1.3%
1
   1.3%
0
   0.0%
2
   1.1%
White
58
  77.3%
60
  80.0%
26
  83.9%
144
  79.6%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
13
  17.3%
14
  18.7%
3
   9.7%
30
  16.6%
1.Primary Outcome
Title Progression Free Survival (PFS) Based on Independent Review Committee (IRC) Assessment - Kaplan Meier Landmark Estimates at Month 54
Hide Description

PFS was defined as the time from date randomization to date of first IRC-confirmed disease progression (PD) assessed according to the modified VIth International Workshop on Waldenström's Macroglobulinemia (IWWM) criteria (National Comprehensive Cancer Network [NCCN] 2014) or death due to any cause, whichever occurs first, regardless of the use of subsequent antineoplastic therapy prior to documented PD or death.

As the median PFS was not reached in the Ibrutinib + Rituximab arm at the time of the analysis, Kaplan Meier landmark estimate of the PFS rate at 54 months (that is, the estimated percentage of participants with PFS at Month 54) is presented.

Time Frame Month 54 (median time on study: 49.7 months [Ibr+R and Pbo+R] and 57.9 months [Open-Label Ibr])
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat population: all randomized/enrolled participants
Arm/Group Title Ibrutinib + Rituximab Placebo + Rituximab Open-Label Substudy: Ibrutinib
Hide Arm/Group Description:

Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment.

Rituximab: 375 mg/m^2 IV per package insert weekly for four consecutive weeks (Day 1 of Weeks 1-4), followed by a second four-weekly rituximab course after a three-month interval (Weeks 17-20) for a total of 8 infusions of rituximab.

Placebo: 3 capsules of placebo orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment.

Rituximab: 375 mg/m^2 IV per package insert weekly for four consecutive weeks (Day 1 of Weeks 1-4), followed by a second four-weekly rituximab course after a three-month interval (Weeks 17-20) for a total of 8 infusions of rituximab.

Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment. Participants (rituximab refractory) were treated in an open-label substudy independently of the 2 randomized main treatment arms.
Overall Number of Participants Analyzed 75 75 31
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
68.0
(54.8 to 78.1)
25.3
(15.3 to 36.6)
39.7
(22.3 to 56.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ibrutinib + Rituximab, Placebo + Rituximab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The treatment effect was tested with a stratified log rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.250
Confidence Interval (2-Sided) 95%
0.148 to 0.420
Estimation Comments The hazard ratio and its 95% confidence interval were based on a Cox regression model stratified by the randomization stratification factors.
2.Secondary Outcome
Title Overall Response Rate (ORR) Based on IRC Assessment Up to 3 Years After Last Participant Randomized
Hide Description ORR, defined as the percentage of participants achieving a best overall response of protocol-specified complete response (CR), very good partial response (VGPR), or partial response (PR) per the IRC assessment at or prior to initiation of subsequent antineoplastic therapy and confirmed by 2 consecutive assessments. IRC assessment of response was conducted according to the modified VIth IWWM (NCCN 2014) criteria and incorporated assessments from the central radiology review. CR required complete resolution of lymphadenopathy/splenomegaly if present at baseline. VGPR and PR required reduction in lymphadenopathy/splenomegaly if present at baseline.. Kaplan-Meier estimate.
Time Frame Median time on study: 49.7 months (Ibr+R and Pbo+R) and 57.9 months (Open-Label Ibr)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat population: all randomized/enrolled participants
Arm/Group Title Ibrutinib + Rituximab Placebo + Rituximab Open-Label Substudy: Ibrutinib
Hide Arm/Group Description:

Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment.

Rituximab: 375 mg/m2 IV per package insert weekly for four consecutive weeks (Day 1 of Weeks 1-4), followed by a second four-weekly rituximab course after a three-month interval (Weeks 17-20) for a total of 8 infusions of rituximab.

Placebo: 3 capsules of placebo orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment.

Rituximab: 375 mg/m2 IV per package insert weekly for four consecutive weeks (Day 1 of Weeks 1-4), followed by a second four-weekly rituximab course after a three-month interval (Weeks 17-20) for a total of 8 infusions of rituximab.

Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment. Participants (rituximab refractory) were treated in an open-label substudy independently of the 2 randomized main treatment arms.
Overall Number of Participants Analyzed 75 75 31
Measure Type: Number
Unit of Measure: percentage of participants
76.0 30.7 77.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ibrutinib + Rituximab, Placebo + Rituximab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Response rate was compared using Cochran-Mantel-Haenszel (CMH) chi-square test.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 2.526
Confidence Interval (2-Sided) 95%
1.753 to 3.639
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Time to Next Treatment (TnT) Time From the Date of Randomization to the Start Date of Any Subsequent WM Treatment.
Hide Description

TTnT was measured from the date of randomization to the start date of any subsequent WM treatment. Participants without subsequent treatment were censored at the date of the last study visit.

As the median TTnT was not reached in the Ibrutinib + Rituximab arm and the Open-Label Substudy arm at the time of the analysis, Kaplan Meier landmark estimate of the TTnT rate at 54 months (that is, the estimated percentage of participants not receiving subsequent WM treatment at Month 54) are presented.

Time Frame Month 54 (median time on study: 49.7 months [Ibr+R and Pbo+R] and 57.9 months [Open-Label Ibr])
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat population: all randomized/enrolled participants
Arm/Group Title Ibrutinib + Rituximab Placebo + Rituximab Open-Label Substudy: Ibrutinib
Hide Arm/Group Description:

Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment.

Rituximab: 375 mg/m^2 IV per package insert weekly for four consecutive weeks (Day 1 of Weeks 1-4), followed by a second four-weekly rituximab course after a three-month interval (Weeks 17-20) for a total of 8 infusions of rituximab.

Placebo: 3 capsules of placebo orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment.

Rituximab: 375 mg/m^2 IV per package insert weekly for four consecutive weeks (Day 1 of Weeks 1-4), followed by a second four-weekly rituximab course after a three-month interval (Weeks 17-20) for a total of 8 infusions of rituximab.

Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment. Participants (rituximab refractory) were treated in an open-label substudy independently of the 2 randomized main treatment arms.
Overall Number of Participants Analyzed 75 75 31
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
87.4
(77.2 to 93.3)
29.4
(18.2 to 41.6)
64.6
(44.1 to 79.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ibrutinib + Rituximab, Placebo + Rituximab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value is from a stratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.102
Confidence Interval (2-Sided) 95%
0.049 to 0.212
Estimation Comments Hazard ratio is estimated using a stratified Cox regression model.
4.Secondary Outcome
Title Percentage of Participants With Sustained Hemoglobin (Hgb) Improvement Up to 3 Years After Last Participant Randomized
Hide Description Percentage of participants achieving a sustained improvement in Hgb at or prior to initiation of subsequent antineoplastic therapy. Hgb improvement is defined as an increase of ≥ 2 g/dL over baseline regardless of baseline value, or an increase to >11 g/dL with a ≥0.5 g/dL improvement if baseline is ≤ 11 g/dL. Sustained Hgb improvement is defined as improvement that is sustained continuously for ≥ 56 days (8 weeks) without blood transfusion or growth factors, which includes hemoglobin > 110 g/L with at least a 5 g/L improvement if baseline ≤110 g/L or increase ≥20 g/L over baseline.
Time Frame Median time on study: 49.7 months (Ibr+R and Pbo+R) and 57.9 months (Open-Label Ibr)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat population: all randomized/enrolled participants
Arm/Group Title Ibrutinib + Rituximab Placebo + Rituximab Open-Label Substudy: Ibrutinib
Hide Arm/Group Description:

Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment.

Rituximab: 375 mg/m^2 IV per package insert weekly for four consecutive weeks (Day 1 of Weeks 1-4), followed by a second four-weekly rituximab course after a three-month interval (Weeks 17-20) for a total of 8 infusions of rituximab.

Placebo: 3 capsules of placebo orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment.

Rituximab: 375 mg/m^2 IV per package insert weekly for four consecutive weeks (Day 1 of Weeks 1-4), followed by a second four-weekly rituximab course after a three-month interval (Weeks 17-20) for a total of 8 infusions of rituximab.

Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment. Participants (rituximab refractory) were treated in an open-label substudy independently of the 2 randomized main treatment arms.
Overall Number of Participants Analyzed 75 75 31
Measure Type: Number
Unit of Measure: percentage of participants
77.3 42.7 71.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ibrutinib + Rituximab, Placebo + Rituximab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 1.813
Confidence Interval (2-Sided) 95%
1.357 to 2.421
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants With ≥ 3 Points Increase From Baseline by Week 25 in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Subscale Score
Hide Description Percentage of participants with ≥ 3 points increase from baseline by Week 25 in the FACIT-Fatigue subscale score.The FACIT-Fatigue is a 13-item questionnaire that assesses participant reported fatigue and its impact upon daily activities and function over the past 7 days. Each of the 13 items of the FACIT-Fatigue Scale ranges from 0-4, with a range of possible total scores from 0 (extreme fatigue) to 52 (no fatigue). Scores below 30 indicate severe fatigue.
Time Frame Baseline, 25 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat population: all randomized/enrolled participants
Arm/Group Title Ibrutinib + Rituximab Placebo + Rituximab Open-Label Substudy: Ibrutinib
Hide Arm/Group Description:

Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment.

Rituximab: 375 mg/m^2 IV per package insert weekly for four consecutive weeks (Day 1 of Weeks 1-4), followed by a second four-weekly rituximab course after a three-month interval (Weeks 17-20) for a total of 8 infusions of rituximab.

Placebo: 3 capsules of placebo orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment.

Rituximab: 375 mg/m^2 IV per package insert weekly for four consecutive weeks (Day 1 of Weeks 1-4), followed by a second four-weekly rituximab course after a three-month interval (Weeks 17-20) for a total of 8 infusions of rituximab.

Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment. Participants (rituximab refractory) were treated in an open-label substudy independently of the 2 randomized main treatment arms.
Overall Number of Participants Analyzed 75 75 31
Measure Type: Number
Unit of Measure: percentage of participants
68.0 54.7 87.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ibrutinib + Rituximab, Placebo + Rituximab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1059
Comments CMH chi squared test
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 1.238
Confidence Interval (2-Sided) 95%
0.955 to 1.603
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Overall Survival (OS) - Kaplan Meier Landmark Estimates at Month 54
Hide Description

OS, defined as the time from the date of randomization to the date of death from any cause. All deaths observed as the time of the analysis were considered as events. For participants who were not known to have died at the time of the analysis, OS data were censored at the date last known alive.

As the median OS was not reached in any treatment arm at the time of the analysis, Kaplan Meier point estimates of the OS rate (that is, the estimated percentage of participants still surviving at Month 54) are presented.

Time Frame Month 54 (median time on study: 49.7 months [Ibr+R and Pbo+R] and 57.9 months [Open-Label Ibr])
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat population: all randomized/enrolled participants
Arm/Group Title Ibrutinib + Rituximab Placebo + Rituximab Open-Label Substudy: Ibrutinib
Hide Arm/Group Description:

Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment.

Rituximab: 375 mg/m^2 IV per package insert weekly for four consecutive weeks (Day 1 of Weeks 1-4), followed by a second four-weekly rituximab course after a three-month interval (Weeks 17-20) for a total of 8 infusions of rituximab.

Placebo: 3 capsules of placebo orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment.

Rituximab: 375 mg/m^2 IV per package insert weekly for four consecutive weeks (Day 1 of Weeks 1-4), followed by a second four-weekly rituximab course after a three-month interval (Weeks 17-20) for a total of 8 infusions of rituximab.

Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment. Participants (rituximab refractory) were treated in an open-label substudy independently of the 2 randomized main treatment arms.
Overall Number of Participants Analyzed 75 75 31
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
86.4
(73.7 to 93.3)
84.2
(71.3 to 91.6)
73.4
(53.7 to 85.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ibrutinib + Rituximab, Placebo + Rituximab
Comments Data cutoff 18 December 2019
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.643
Comments P-value is from unstratified log rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.808
Confidence Interval (2-Sided) 95%
0.328 to 1.99
Estimation Comments Hazard ratio is estimated using unstratified Cox regression model with treatment as the only covariate.
Time Frame From first dose of study drug up to 30 days after the last dose of study drug. Median duration of treatment was 47.7 months for the Ibr+R arm, 15.5 months for the Pbo+R arm, and 40.7 months for the Open-Label Ibr arm.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Ibrutinib + Rituximab Placebo + Rituximab Open-Label Substudy: Ibrutinib
Hide Arm/Group Description

Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment.

Rituximab: 375 mg/m^2 IV per package insert weekly for four consecutive weeks (Day 1 of Weeks 1-4), followed by a second four-weekly rituximab course after a three-month interval (Weeks 17-20) for a total of 8 infusions of rituximab.

Placebo: 3 capsules of placebo orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment.

Rituximab: 375 mg/m^2 IV per package insert weekly for four consecutive weeks (Day 1 of Weeks 1-4), followed by a second four-weekly rituximab course after a three-month interval (Weeks 17-20) for a total of 8 infusions of rituximab.

Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1 in Week 1 until progression, discontinuation due to toxicity or other reasons to discontinue treatment.
All-Cause Mortality
Ibrutinib + Rituximab Placebo + Rituximab Open-Label Substudy: Ibrutinib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   9/75 (12.00%)   10/75 (13.33%)   8/31 (25.81%) 
Hide Serious Adverse Events
Ibrutinib + Rituximab Placebo + Rituximab Open-Label Substudy: Ibrutinib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   40/75 (53.33%)   25/75 (33.33%)   16/31 (51.61%) 
Blood and lymphatic system disorders       
Anaemia  1  2/75 (2.67%)  0/75 (0.00%)  0/31 (0.00%) 
Febrile neutropenia  1  0/75 (0.00%)  0/75 (0.00%)  1/31 (3.23%) 
Immune thrombocytopenic purpura  1  0/75 (0.00%)  1/75 (1.33%)  0/31 (0.00%) 
Leukopenia  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Neutropenia  1  0/75 (0.00%)  0/75 (0.00%)  1/31 (3.23%) 
Thrombocytopenia  1  0/75 (0.00%)  0/75 (0.00%)  1/31 (3.23%) 
Cardiac disorders       
Angina pectoris  1  0/75 (0.00%)  1/75 (1.33%)  0/31 (0.00%) 
Angina unstable  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Atrial fibrillation  1  8/75 (10.67%)  1/75 (1.33%)  0/31 (0.00%) 
Cardiac failure  1  2/75 (2.67%)  0/75 (0.00%)  0/31 (0.00%) 
Cardiac tamponade  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Coronary artery disease  1  0/75 (0.00%)  1/75 (1.33%)  0/31 (0.00%) 
Left ventricular failure  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Myocardial infarction  1  0/75 (0.00%)  1/75 (1.33%)  0/31 (0.00%) 
Myocardial ischaemia  1  2/75 (2.67%)  0/75 (0.00%)  0/31 (0.00%) 
Pericarditis  1  0/75 (0.00%)  1/75 (1.33%)  0/31 (0.00%) 
Prinzmetal angina  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Congenital, familial and genetic disorders       
Hypertrophic cardiomyopathy  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Eye disorders       
Ulcerative keratitis  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Gastrointestinal disorders       
Abdominal pain  1  0/75 (0.00%)  1/75 (1.33%)  0/31 (0.00%) 
Abdominal pain upper  1  0/75 (0.00%)  0/75 (0.00%)  1/31 (3.23%) 
Constipation  1  1/75 (1.33%)  1/75 (1.33%)  1/31 (3.23%) 
Diarrhoea  1  0/75 (0.00%)  1/75 (1.33%)  1/31 (3.23%) 
Faecalith  1  0/75 (0.00%)  0/75 (0.00%)  1/31 (3.23%) 
Gastrointestinal haemorrhage  1  0/75 (0.00%)  1/75 (1.33%)  0/31 (0.00%) 
Ileus  1  0/75 (0.00%)  0/75 (0.00%)  1/31 (3.23%) 
Melaena  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
General disorders       
Asthenia  1  0/75 (0.00%)  0/75 (0.00%)  1/31 (3.23%) 
Death  1 [1]  0/75 (0.00%)  1/75 (1.33%)  0/31 (0.00%) 
Fatigue  1  0/75 (0.00%)  1/75 (1.33%)  0/31 (0.00%) 
Gait disturbance  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
General physical health deterioration  1  1/75 (1.33%)  1/75 (1.33%)  0/31 (0.00%) 
Oedema peripheral  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Pyrexia  1  2/75 (2.67%)  0/75 (0.00%)  0/31 (0.00%) 
Hepatobiliary disorders       
Cholecystitis  1  1/75 (1.33%)  1/75 (1.33%)  0/31 (0.00%) 
Cholecystitis acute  1  1/75 (1.33%)  0/75 (0.00%)  1/31 (3.23%) 
Infections and infestations       
Arthritis bacterial  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Atypical pneumonia  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Cellulitis  1  2/75 (2.67%)  0/75 (0.00%)  1/31 (3.23%) 
Clostridium difficile colitis  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Enterococcal sepsis  1  0/75 (0.00%)  1/75 (1.33%)  0/31 (0.00%) 
Erysipelas  1  2/75 (2.67%)  0/75 (0.00%)  0/31 (0.00%) 
Escherichia sepsis  1  0/75 (0.00%)  0/75 (0.00%)  1/31 (3.23%) 
Gastroenteritis  1  2/75 (2.67%)  0/75 (0.00%)  0/31 (0.00%) 
Hemianopia  1  0/75 (0.00%)  0/75 (0.00%)  1/31 (3.23%) 
Orchitis  1  0/75 (0.00%)  0/75 (0.00%)  1/31 (3.23%) 
Osteomyelitis  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Pneumonia  1  8/75 (10.67%)  2/75 (2.67%)  1/31 (3.23%) 
Pneumonia bacterial  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Pneumonia pneumococcal  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Pneumonia viral  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Prostatic abscess  1  0/75 (0.00%)  0/75 (0.00%)  1/31 (3.23%) 
Pulmonary sepsis  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Respiratory syncytial virus infection  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Respiratory tract infection  1  4/75 (5.33%)  0/75 (0.00%)  1/31 (3.23%) 
Sepsis  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Septic shock  1  0/75 (0.00%)  1/75 (1.33%)  0/31 (0.00%) 
Staphylococcal bacteraemia  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Staphylococcal sepsis  1  0/75 (0.00%)  1/75 (1.33%)  0/31 (0.00%) 
Streptococcal bacteraemia  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Subcutaneous abscess  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Upper respiratory tract infection  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Urosepsis  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Injury, poisoning and procedural complications       
Fall  1  3/75 (4.00%)  0/75 (0.00%)  0/31 (0.00%) 
Femur fracture  1  1/75 (1.33%)  0/75 (0.00%)  1/31 (3.23%) 
Infusion related reaction  1  0/75 (0.00%)  5/75 (6.67%)  0/31 (0.00%) 
Lower limb fracture  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Pelvic fracture  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Spinal compression fracture  1  0/75 (0.00%)  1/75 (1.33%)  0/31 (0.00%) 
Spinal fracture  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Subdural haematoma  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Tendon injury  1  0/75 (0.00%)  1/75 (1.33%)  0/31 (0.00%) 
Investigations       
Neutrophil count decreased  1  0/75 (0.00%)  1/75 (1.33%)  0/31 (0.00%) 
Metabolism and nutrition disorders       
Dehydration  1  0/75 (0.00%)  1/75 (1.33%)  1/31 (3.23%) 
Fluid overload  1  0/75 (0.00%)  1/75 (1.33%)  0/31 (0.00%) 
Hyponatraemia  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Lactic acidosis  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  3/75 (4.00%)  0/75 (0.00%)  0/31 (0.00%) 
Breast cancer metastatic  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Fracture pain  1  0/75 (0.00%)  1/75 (1.33%)  0/31 (0.00%) 
Joint swelling  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Mobility decreased  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Musculoskeletal chest pain  1  0/75 (0.00%)  0/75 (0.00%)  1/31 (3.23%) 
Psoriatic arthropathy  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Soft tissue necrosis  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Synovial cyst  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Tendonitis  1  0/75 (0.00%)  1/75 (1.33%)  0/31 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Benign pancreatic neoplasm  1  0/75 (0.00%)  1/75 (1.33%)  0/31 (0.00%) 
Bing-Neel syndrome  1  0/75 (0.00%)  1/75 (1.33%)  0/31 (0.00%) 
Breast cancer  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Diffuse large B-cell lymphoma  1  0/75 (0.00%)  0/75 (0.00%)  1/31 (3.23%) 
Invasive lobular breast carcinoma  1  0/75 (0.00%)  1/75 (1.33%)  0/31 (0.00%) 
Prostate cancer  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Renal cell carcinoma  1  0/75 (0.00%)  0/75 (0.00%)  1/31 (3.23%) 
Small cell lung cancer  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Squamous cell carcinoma  1  1/75 (1.33%)  1/75 (1.33%)  0/31 (0.00%) 
Nervous system disorders       
Aphasia  1  0/75 (0.00%)  0/75 (0.00%)  1/31 (3.23%) 
Haemorrhage intracranial  1  0/75 (0.00%)  1/75 (1.33%)  0/31 (0.00%) 
Lumbar radiculopathy  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Syncope  1  1/75 (1.33%)  0/75 (0.00%)  2/31 (6.45%) 
Transient ischaemic attack  1  0/75 (0.00%)  0/75 (0.00%)  1/31 (3.23%) 
Renal and urinary disorders       
Acute kidney injury  1  2/75 (2.67%)  0/75 (0.00%)  0/31 (0.00%) 
Dysuria  1  0/75 (0.00%)  1/75 (1.33%)  0/31 (0.00%) 
Haematuria  1  0/75 (0.00%)  1/75 (1.33%)  0/31 (0.00%) 
Urinary retention  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Reproductive system and breast disorders       
Prostatitis  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Bronchopneumopathy  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Dyspnoea  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Epistaxis  1  1/75 (1.33%)  1/75 (1.33%)  0/31 (0.00%) 
Lung disorder  1  2/75 (2.67%)  0/75 (0.00%)  0/31 (0.00%) 
Pleural effusion  1  0/75 (0.00%)  1/75 (1.33%)  1/31 (3.23%) 
Pulmonary oedema  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Skin and subcutaneous tissue disorders       
Eczema  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Purpura  1  1/75 (1.33%)  0/75 (0.00%)  0/31 (0.00%) 
Vascular disorders       
Circulatory collapse  1  0/75 (0.00%)  1/75 (1.33%)  0/31 (0.00%) 
Hypertension  1  1/75 (1.33%)  1/75 (1.33%)  0/31 (0.00%) 
Hypotension  1  0/75 (0.00%)  1/75 (1.33%)  0/31 (0.00%) 
1
Term from vocabulary, MedDRA 22.1
Indicates events were collected by systematic assessment
[1]
Cause of death unknown
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ibrutinib + Rituximab Placebo + Rituximab Open-Label Substudy: Ibrutinib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   75/75 (100.00%)   75/75 (100.00%)   30/31 (96.77%) 
Blood and lymphatic system disorders       
Anaemia  1  17/75 (22.67%)  21/75 (28.00%)  5/31 (16.13%) 
Increased tendency to bruise  1  9/75 (12.00%)  2/75 (2.67%)  8/31 (25.81%) 
Lymphadenopathy  1  0/75 (0.00%)  0/75 (0.00%)  2/31 (6.45%) 
Neutropenia  1  12/75 (16.00%)  7/75 (9.33%)  9/31 (29.03%) 
Spontaneous haematoma  1  0/75 (0.00%)  0/75 (0.00%)  2/31 (6.45%) 
Thrombocytopenia  1  5/75 (6.67%)  8/75 (10.67%)  6/31 (19.35%) 
Cardiac disorders       
Atrial fibrillation  1  11/75 (14.67%)  1/75 (1.33%)  0/31 (0.00%) 
Palpitations  1  4/75 (5.33%)  0/75 (0.00%)  2/31 (6.45%) 
Ear and labyrinth disorders       
Tinnitus  1  0/75 (0.00%)  0/75 (0.00%)  4/31 (12.90%) 
Eye disorders       
Cataract  1  7/75 (9.33%)  1/75 (1.33%)  4/31 (12.90%) 
Diplopia  1  0/75 (0.00%)  0/75 (0.00%)  2/31 (6.45%) 
Dry eye  1  5/75 (6.67%)  5/75 (6.67%)  3/31 (9.68%) 
Eye irritation  1  6/75 (8.00%)  1/75 (1.33%)  0/31 (0.00%) 
Lacrimation increased  1  9/75 (12.00%)  3/75 (4.00%)  0/31 (0.00%) 
Photophobia  1  6/75 (8.00%)  2/75 (2.67%)  0/31 (0.00%) 
Vision blurred  1  7/75 (9.33%)  2/75 (2.67%)  4/31 (12.90%) 
Visual acuity reduced  1  9/75 (12.00%)  3/75 (4.00%)  0/31 (0.00%) 
Vitreous detachment  1  0/75 (0.00%)  0/75 (0.00%)  2/31 (6.45%) 
Vitreous floaters  1  4/75 (5.33%)  2/75 (2.67%)  2/31 (6.45%) 
Gastrointestinal disorders       
Abdominal discomfort  1  0/75 (0.00%)  0/75 (0.00%)  3/31 (9.68%) 
Abdominal distension  1  0/75 (0.00%)  0/75 (0.00%)  2/31 (6.45%) 
Abdominal pain  1  4/75 (5.33%)  2/75 (2.67%)  4/31 (12.90%) 
Abdominal pain upper  1  4/75 (5.33%)  2/75 (2.67%)  2/31 (6.45%) 
Constipation  1  9/75 (12.00%)  9/75 (12.00%)  5/31 (16.13%) 
Diarrhoea  1  23/75 (30.67%)  11/75 (14.67%)  14/31 (45.16%) 
Dry mouth  1  4/75 (5.33%)  0/75 (0.00%)  0/31 (0.00%) 
Dyspepsia  1  13/75 (17.33%)  1/75 (1.33%)  2/31 (6.45%) 
Gastritis  1  4/75 (5.33%)  0/75 (0.00%)  0/31 (0.00%) 
Gastrooesophageal reflux disease  1  7/75 (9.33%)  1/75 (1.33%)  3/31 (9.68%) 
Gingival bleeding  1  0/75 (0.00%)  0/75 (0.00%)  2/31 (6.45%) 
Nausea  1  17/75 (22.67%)  9/75 (12.00%)  7/31 (22.58%) 
Stomatitis  1  4/75 (5.33%)  1/75 (1.33%)  0/31 (0.00%) 
Vomiting  1  5/75 (6.67%)  8/75 (10.67%)  0/31 (0.00%) 
General disorders       
Asthenia  1  12/75 (16.00%)  19/75 (25.33%)  4/31 (12.90%) 
Chest pain  1  4/75 (5.33%)  0/75 (0.00%)  0/31 (0.00%) 
Chills  1  0/75 (0.00%)  0/75 (0.00%)  2/31 (6.45%) 
Fatigue  1  13/75 (17.33%)  18/75 (24.00%)  5/31 (16.13%) 
Influenza like illness  1  4/75 (5.33%)  4/75 (5.33%)  0/31 (0.00%) 
Oedema peripheral  1  17/75 (22.67%)  9/75 (12.00%)  5/31 (16.13%) 
Pyrexia  1  12/75 (16.00%)  12/75 (16.00%)  11/31 (35.48%) 
Infections and infestations       
Bronchitis  1  11/75 (14.67%)  5/75 (6.67%)  3/31 (9.68%) 
Cellulitis  1  4/75 (5.33%)  1/75 (1.33%)  3/31 (9.68%) 
Conjunctivitis  1  4/75 (5.33%)  3/75 (4.00%)  4/31 (12.90%) 
Folliculitis  1  4/75 (5.33%)  1/75 (1.33%)  0/31 (0.00%) 
Herpes zoster  1  6/75 (8.00%)  1/75 (1.33%)  2/31 (6.45%) 
Influenza  1  10/75 (13.33%)  5/75 (6.67%)  2/31 (6.45%) 
Localised infection  1  0/75 (0.00%)  0/75 (0.00%)  2/31 (6.45%) 
Nasopharyngitis  1  12/75 (16.00%)  7/75 (9.33%)  3/31 (9.68%) 
Oral herpes  1  6/75 (8.00%)  0/75 (0.00%)  0/31 (0.00%) 
Paronychia  1  0/75 (0.00%)  0/75 (0.00%)  2/31 (6.45%) 
Pneumonia  1  5/75 (6.67%)  2/75 (2.67%)  2/31 (6.45%) 
Respiratory tract infection  1  6/75 (8.00%)  2/75 (2.67%)  5/31 (16.13%) 
Respiratory tract infection viral  1  0/75 (0.00%)  0/75 (0.00%)  2/31 (6.45%) 
Rhinitis  1  4/75 (5.33%)  1/75 (1.33%)  2/31 (6.45%) 
Sinusitis  1  4/75 (5.33%)  2/75 (2.67%)  4/31 (12.90%) 
Upper respiratory tract infection  1  10/75 (13.33%)  3/75 (4.00%)  6/31 (19.35%) 
Urinary tract infection  1  11/75 (14.67%)  0/75 (0.00%)  3/31 (9.68%) 
Injury, poisoning and procedural complications       
Contusion  1  7/75 (9.33%)  1/75 (1.33%)  2/31 (6.45%) 
Fall  1  7/75 (9.33%)  3/75 (4.00%)  3/31 (9.68%) 
Infusion related reaction  1  32/75 (42.67%)  43/75 (57.33%)  0/31 (0.00%) 
Traumatic haematoma  1  5/75 (6.67%)  0/75 (0.00%)  0/31 (0.00%) 
Investigations       
Blood Creatinine Increased  1  5/75 (6.67%)  0/75 (0.00%)  0/31 (0.00%) 
Blood Uric Acid Increased  1  4/75 (5.33%)  0/75 (0.00%)  0/31 (0.00%) 
Metabolism and nutrition disorders       
Decreased appetite  1  3/75 (4.00%)  7/75 (9.33%)  3/31 (9.68%) 
Gout  1  4/75 (5.33%)  1/75 (1.33%)  0/31 (0.00%) 
Hyperuricaemia  1  4/75 (5.33%)  4/75 (5.33%)  2/31 (6.45%) 
Hypokalaemia  1  9/75 (12.00%)  1/75 (1.33%)  2/31 (6.45%) 
Hyponatraemia  1  5/75 (6.67%)  2/75 (2.67%)  0/31 (0.00%) 
Iron deficiency  1  4/75 (5.33%)  0/75 (0.00%)  0/31 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  19/75 (25.33%)  9/75 (12.00%)  7/31 (22.58%) 
Back pain  1  13/75 (17.33%)  7/75 (9.33%)  9/31 (29.03%) 
Muscle spasms  1  16/75 (21.33%)  9/75 (12.00%)  5/31 (16.13%) 
Muscular weakness  1  0/75 (0.00%)  0/75 (0.00%)  2/31 (6.45%) 
Musculoskeletal chest pain  1  0/75 (0.00%)  0/75 (0.00%)  2/31 (6.45%) 
Myalgia  1  5/75 (6.67%)  3/75 (4.00%)  2/31 (6.45%) 
Osteoarthritis  1  4/75 (5.33%)  1/75 (1.33%)  0/31 (0.00%) 
Pain in extremity  1  10/75 (13.33%)  6/75 (8.00%)  5/31 (16.13%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Basal cell carcinoma  1  4/75 (5.33%)  4/75 (5.33%)  0/31 (0.00%) 
Tumour flare  1  6/75 (8.00%)  35/75 (46.67%)  0/31 (0.00%) 
Nervous system disorders       
Dizziness  1  10/75 (13.33%)  6/75 (8.00%)  4/31 (12.90%) 
Headache  1  13/75 (17.33%)  17/75 (22.67%)  7/31 (22.58%) 
Paraesthesia  1  4/75 (5.33%)  4/75 (5.33%)  2/31 (6.45%) 
Peripheral sensory neuropathy  1  5/75 (6.67%)  4/75 (5.33%)  2/31 (6.45%) 
Sciatica  1  6/75 (8.00%)  0/75 (0.00%)  3/31 (9.68%) 
Psychiatric disorders       
Depression  1  0/75 (0.00%)  0/75 (0.00%)  3/31 (9.68%) 
Insomnia  1  12/75 (16.00%)  3/75 (4.00%)  2/31 (6.45%) 
Renal and urinary disorders       
Haematuria  1  0/75 (0.00%)  0/75 (0.00%)  2/31 (6.45%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  16/75 (21.33%)  8/75 (10.67%)  9/31 (29.03%) 
Dyspnoea  1  8/75 (10.67%)  10/75 (13.33%)  3/31 (9.68%) 
Epistaxis  1  8/75 (10.67%)  7/75 (9.33%)  4/31 (12.90%) 
Oropharyngeal pain  1  4/75 (5.33%)  2/75 (2.67%)  3/31 (9.68%) 
Productive cough  1  3/75 (4.00%)  4/75 (5.33%)  0/31 (0.00%) 
Rhinorrhoea  1  5/75 (6.67%)  5/75 (6.67%)  2/31 (6.45%) 
Skin and subcutaneous tissue disorders       
Actinic keratosis  1  0/75 (0.00%)  0/75 (0.00%)  2/31 (6.45%) 
Dermatitis contact  1  0/75 (0.00%)  0/75 (0.00%)  2/31 (6.45%) 
Dry skin  1  0/75 (0.00%)  0/75 (0.00%)  6/31 (19.35%) 
Ecchymosis  1  9/75 (12.00%)  0/75 (0.00%)  0/31 (0.00%) 
Onychoclasis  1  0/75 (0.00%)  0/75 (0.00%)  4/31 (12.90%) 
Onycholysis  1  0/75 (0.00%)  0/75 (0.00%)  2/31 (6.45%) 
Petechiae  1  7/75 (9.33%)  0/75 (0.00%)  4/31 (12.90%) 
Pruritus  1  6/75 (8.00%)  4/75 (5.33%)  2/31 (6.45%) 
Psoriasis  1  0/75 (0.00%)  0/75 (0.00%)  2/31 (6.45%) 
Rash erythematous  1  7/75 (9.33%)  2/75 (2.67%)  0/31 (0.00%) 
Rash maculo-papular  1  5/75 (6.67%)  3/75 (4.00%)  3/31 (9.68%) 
Skin lesion  1  4/75 (5.33%)  0/75 (0.00%)  0/31 (0.00%) 
Vascular disorders       
Hypertension  1  18/75 (24.00%)  3/75 (4.00%)  8/31 (25.81%) 
Hypotension  1  0/75 (0.00%)  0/75 (0.00%)  3/31 (9.68%) 
1
Term from vocabulary, MedDRA 22.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
  1. Institution/Investigator will not publish without Sponsor prior review and approval
  2. Institution/Investigator will not publish until the earlier of (i) results of study are submitted for publication (ii) notification that submission of the multicenter results are no longer planned (iii) 18 months after study termination.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Lori Styles
Organization: Pharmacyclics LLC, An AbbVie Company
Phone: (408) 215-3770
EMail: lstyles@pcyc.com
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Responsible Party: Pharmacyclics LLC.
ClinicalTrials.gov Identifier: NCT02165397    
Other Study ID Numbers: PCYC-1127-CA
First Submitted: June 9, 2014
First Posted: June 17, 2014
Results First Submitted: October 20, 2020
Results First Posted: November 16, 2020
Last Update Posted: March 3, 2021