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Trial record 25 of 143 for:    Venetoclax AND Leukemia

A Study to Evaluate the Benefit of Venetoclax Plus Rituximab Compared With Bendamustine Plus Rituximab in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) (MURANO)

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ClinicalTrials.gov Identifier: NCT02005471
Recruitment Status : Active, not recruiting
First Posted : December 9, 2013
Results First Posted : October 1, 2018
Last Update Posted : September 9, 2019
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Chronic Lymphocytic Leukemia
Interventions Drug: Bendamustine
Drug: Venetoclax
Drug: Rituximab
Enrollment 389
Recruitment Details A total of 489 participants were screened, out of which, 389 participants were enrolled into the study.
Pre-assignment Details  
Arm/Group Title Bendamustine + Rituximab Venetoclax + Rituximab
Hide Arm/Group Description Participants received bendamustine at a dose of 70 milligrams per meter squared (mg/m^2) via intravenous (IV) infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6. Participants were initially placed on a venetoclax ramp-up period of 5 weeks, and received an initial dose of 20 milligrams (mg) via tablet orally once daily (QD) for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to disease progression (PD) or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Period Title: Overall Study
Started 195 194
Treated 188 194
Completed 0 0
Not Completed 195 194
Reason Not Completed
Ongoing in Study             144             171
Adverse Event             1             0
Death             26             15
Lost to Follow-up             1             0
Physician Decision             2             1
Progressive Disease             3             0
Withdrawal by Subject             18             7
Arm/Group Title Bendamustine + Rituximab Venetoclax + Rituximab Total
Hide Arm/Group Description Participants received bendamustine at a dose of 70 mg/m^2 via IV infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6. Participants were initially placed on a venetoclax ramp-up period of 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6. Total of all reporting groups
Overall Number of Baseline Participants 195 194 389
Hide Baseline Analysis Population Description
Analysis was performed on intent-to-treat (ITT) population, which included all randomized participants, with participants grouped according to randomized treatment group, regardless of the actual treatment received.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 195 participants 194 participants 389 participants
64.4  (9.6) 63.9  (10.5) 64.1  (10.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 195 participants 194 participants 389 participants
Female
44
  22.6%
58
  29.9%
102
  26.2%
Male
151
  77.4%
136
  70.1%
287
  73.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 195 participants 194 participants 389 participants
Hispanic or Latino
3
   1.5%
4
   2.1%
7
   1.8%
Not Hispanic or Latino
186
  95.4%
186
  95.9%
372
  95.6%
Unknown or Not Reported
6
   3.1%
4
   2.1%
10
   2.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 195 participants 194 participants 389 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
4
   2.1%
6
   3.1%
10
   2.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
   1.0%
0
   0.0%
2
   0.5%
White
178
  91.3%
181
  93.3%
359
  92.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
11
   5.6%
7
   3.6%
18
   4.6%
1.Primary Outcome
Title Percentage of Participants With PD as Assessed by the Investigator Using Standard International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Guidelines or Death
Hide Description Assessment of response was performed by the investigator according to the iwCLL guidelines. PD was defined as occurrence of one of the following events: appearance of any new extra nodal lesion; new palpable lymph node (greater than [>] 1.5 centimeters [cm]); unequivocal progression of non-target lesion; an increase of greater than or equal to (>/=) 50 percent (%) compared to baseline in splenomegaly, hepatomegaly, number of blood lymphocytes with lymphocyte count >/=5000 per microliter (mcL), or in longest diameter of any extra nodal lesion; transformation to a more aggressive histology; decrease of >/=50% compared to baseline in platelet or neutrophil count; or decrease in hemoglobin level by >2 grams per deciliter (g/dL) or to less than [<] 10 g/dL.
Time Frame Baseline up to PD or death from any cause, whichever occurred first (up to approximately 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population.
Arm/Group Title Bendamustine + Rituximab Venetoclax + Rituximab
Hide Arm/Group Description:
Participants received bendamustine at a dose of 70 mg/m^2 via IV infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Participants were initially placed on a venetoclax ramp-up period of 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Overall Number of Participants Analyzed 195 194
Measure Type: Number
Unit of Measure: percentage of participants
58.5 16.5
2.Primary Outcome
Title Progression-Free Survival (PFS) as Assessed by the Investigator Using Standard iwCLL Guidelines
Hide Description PFS was defined as the time from randomization until first occurrence of PD/relapse as assessed by the investigator using iwCLL guidelines, or death from any cause, whichever occurred first. PD: occurrence of one of the following: new lesion; new palpable lymph node (>1.5 cm); unequivocal progression of non-target lesion; increase of >/=50% in splenomegaly, hepatomegaly, blood lymphocytes with count >/=5000/mcL, longest diameter of any lesion; transformation to more aggressive histology; decrease of >/=50% in platelet or neutrophil count, or hemoglobin level by >2 g/dL or to <10 g/dL. Participants who had not progressed, relapsed, or died at the time of analysis, were censored on the date of last assessment. In case of no disease assessment after baseline, PFS was censored at the time of randomization+1 day. The median PFS was estimated using Kaplan-Meier method and the 95% confidence interval (CI) was computed using method of Brookmeyer and Crowley.
Time Frame Baseline up to PD or death, whichever occurred first (up to approximately 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population.
Arm/Group Title Bendamustine + Rituximab Venetoclax + Rituximab
Hide Arm/Group Description:
Participants received bendamustine at a dose of 70 mg/m^2 via IV infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Participants were initially placed on a venetoclax ramp-up period of 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Overall Number of Participants Analyzed 195 194
Median (95% Confidence Interval)
Unit of Measure: months
17.0
(15.5 to 21.6)
NA [1] 
(NA to NA)
[1]
Median and corresponding 95% CI could not be estimated due to low number of participants with an event.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bendamustine + Rituximab, Venetoclax + Rituximab
Comments Stratified Analysis; Stratification factors: 17p deletion, risk status, geographic region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.17
Confidence Interval (2-Sided) 95%
0.11 to 0.25
Estimation Comments Hazard ratio was estimated by Cox regression model.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bendamustine + Rituximab, Venetoclax + Rituximab
Comments Unstratified Analysis
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.17
Confidence Interval (2-Sided) 95%
0.12 to 0.26
Estimation Comments Hazard ratio was estimated by Cox regression model.
3.Secondary Outcome
Title Percentage of Participants With PD or Death as Assessed by the Independent Review Committee (IRC) Using Standard iwCLL Guidelines
Hide Description Assessment of response was performed by the IRC according to the iwCLL guidelines. PD was defined as occurrence of one of the following events: appearance of any new extra nodal lesion; new palpable lymph node (>1.5 cm); unequivocal progression of non-target lesion; an increase of >/=50% compared to baseline in splenomegaly, hepatomegaly, number of blood lymphocytes with lymphocyte count >/=5000/mcL, or in longest diameter of any extra nodal lesion; transformation to a more aggressive histology; decrease of >/=50% compared to baseline in platelet or neutrophil count; or decrease in hemoglobin level by >2 g/dL or to <10 g/dL.
Time Frame Baseline up to PD or death, whichever occurred first (up to approximately 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population.
Arm/Group Title Bendamustine + Rituximab Venetoclax + Rituximab
Hide Arm/Group Description:
Participants received bendamustine at a dose of 70 mg/m^2 via IV infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Participants were initially placed on a venetoclax ramp-up period of 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Overall Number of Participants Analyzed 195 194
Measure Type: Number
Unit of Measure: percentage of participants
54.4 18.0
4.Secondary Outcome
Title PFS as Assessed by the IRC Using Standard iwCLL Guidelines
Hide Description PFS was defined as the time from randomization until first occurrence of PD/relapse as assessed by the IRC using iwCLL guidelines, or death from any cause, whichever occurred first. PD: occurrence of one of the following: new lesion; new palpable lymph node (>1.5 cm); unequivocal progression of non-target lesion; increase of >/=50% in splenomegaly, hepatomegaly, blood lymphocytes with count >/=5000/mcL, longest diameter of any lesion; transformation to more aggressive histology; decrease of >/=50% in platelet or neutrophil count, or hemoglobin level by >2 g/dL or to <10 g/dL. Participants who had not progressed, relapsed, or died at the time of analysis, were censored on the date of last assessment. In case of no disease assessment after baseline, PFS was censored at the time of randomization+1 day. The median PFS was estimated using Kaplan-Meier method and the 95% CI was computed using method of Brookmeyer and Crowley.
Time Frame Baseline up to PD or death, whichever occurred first (up to approximately 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population.
Arm/Group Title Bendamustine + Rituximab Venetoclax + Rituximab
Hide Arm/Group Description:
Participants received bendamustine at a dose of 70 mg/m^2 via IV infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Participants were initially placed on a venetoclax ramp-up period of 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Overall Number of Participants Analyzed 195 194
Median (95% Confidence Interval)
Unit of Measure: months
18.1
(15.8 to 22.3)
NA [1] 
(NA to NA)
[1]
Median and corresponding 95% CI could not be estimated due to low number of participants with an event.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bendamustine + Rituximab, Venetoclax + Rituximab
Comments Stratified Analysis; Stratification factors: 17p deletion, risk status, geographic region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.19
Confidence Interval (2-Sided) 95%
0.13 to 0.28
Estimation Comments Hazard ratio was estimated by Cox regression model.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bendamustine + Rituximab, Venetoclax + Rituximab
Comments Unstratified Analysis
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.20
Confidence Interval (2-Sided) 95%
0.14 to 0.30
Estimation Comments Hazard ratio was estimated by Cox regression model.
5.Secondary Outcome
Title Percentage of Participants With PD or Death as Assessed by the Investigator Using Standard iwCLL Guidelines in Participants With 17p Deletion as Identified by Fluorescence In-situ Hybridization (FISH) Test
Hide Description Assessment of response was performed by the investigator according to the iwCLL guidelines. PD was defined as occurrence of one of the following events: appearance of any new extra nodal lesion; new palpable lymph node (>1.5 cm); unequivocal progression of non-target lesion; an increase of >/=50% compared to baseline in splenomegaly, hepatomegaly, number of blood lymphocytes with lymphocyte count >/=5000/mcL, or in longest diameter of any extra nodal lesion; transformation to a more aggressive histology; decrease of >/=50% compared to baseline in platelet or neutrophil count; or decrease in hemoglobin level by >2 g/dL or to <10 g/dL.
Time Frame Baseline up to PD or death, whichever occurred first (up to approximately 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population participants with 17p deletion as identified by FISH test.
Arm/Group Title Bendamustine + Rituximab 17p Del. Population Venetoclax + Rituximab 17p Del. Population
Hide Arm/Group Description:
Participants received bendamustine at a dose of 70 mg/m^2 via IV infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6. Only participants with 17p deletion as identified by FISH test were included.
Participants were initially placed on a venetoclax ramp-up period of 4 to 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6. Only participants with 17p deletion as identified by FISH test were included.
Overall Number of Participants Analyzed 46 46
Measure Type: Number
Unit of Measure: percentage of participants
58.7 15.2
6.Secondary Outcome
Title PFS as Assessed by the Investigator Using Standard iwCLL Guidelines in Participants With 17p Deletion as Identified by FISH Test
Hide Description PFS was defined as the time from randomization until first occurrence of PD/relapse as assessed by the investigator using iwCLL guidelines, or death from any cause, whichever occurred first. PD: occurrence of one of the following: new lesion; new palpable lymph node (>1.5 cm); unequivocal progression of non-target lesion; increase of >/=50% in splenomegaly, hepatomegaly, blood lymphocytes with count >/=5000/mcL, longest diameter of any lesion; transformation to more aggressive histology; decrease of >/=50% in platelet or neutrophil count, or hemoglobin level by >2 g/dL or to <10 g/dL. Participants who had not progressed, relapsed, or died at the time of analysis, were censored on the date of last assessment. In case of no disease assessment after baseline, PFS was censored at the time of randomization+1 day. The median PFS was estimated using Kaplan-Meier method and the 95% CI was computed using method of Brookmeyer and Crowley.
Time Frame Baseline up to PD or death, whichever occurred first (up to approximately 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population participants with 17p deletion as identified by FISH test.
Arm/Group Title Bendamustine + Rituximab 17p Del. Population Venetoclax + Rituximab 17p Del. Population
Hide Arm/Group Description:
Participants received bendamustine at a dose of 70 mg/m^2 via IV infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6. Only participants with 17p deletion as identified by FISH test were included.
Participants were initially placed on a venetoclax ramp-up period of 4 to 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6. Only participants with 17p deletion as identified by FISH test were included.
Overall Number of Participants Analyzed 46 46
Median (95% Confidence Interval)
Unit of Measure: months
15.4
(10.0 to 21.0)
NA [1] 
(27.6 to NA)
[1]
Median and Upper Limit of 95% CI could not be estimated due to low number of participants with an event.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bendamustine + Rituximab 17p Del. Population, Venetoclax + Rituximab 17p Del. Population
Comments Stratified Analysis; Stratification factor: geographic region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.13
Confidence Interval (2-Sided) 95%
0.05 to 0.31
Estimation Comments Hazard ratio was estimated by Cox regression model.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bendamustine + Rituximab 17p Del. Population, Venetoclax + Rituximab 17p Del. Population
Comments Unstratified Analysis
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.13
Confidence Interval (2-Sided) 95%
0.05 to 0.29
Estimation Comments Hazard ratio was estimated by Cox regression model.
7.Secondary Outcome
Title Percentage of Participants With PD or Death as Assessed by the IRC Using Standard iwCLL Guidelines in Participants With 17p Deletion as Identified by FISH Test
Hide Description Assessment of response was performed by the IRC according to the iwCLL guidelines. PD was defined as occurrence of one of the following events: appearance of any new extra nodal lesion; new palpable lymph node (>1.5 cm); unequivocal progression of non-target lesion; an increase of >/=50% compared to baseline in splenomegaly, hepatomegaly, number of blood lymphocytes with lymphocyte count >/=5000/mcL, or in longest diameter of any extra nodal lesion; transformation to a more aggressive histology; decrease of >/=50% compared to baseline in platelet or neutrophil count; or decrease in hemoglobin level by >2 g/dL or to <10 g/dL.
Time Frame Baseline up to PD or death, whichever occurred first (up to approximately 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population participants with 17p deletion as identified by FISH test.
Arm/Group Title Bendamustine + Rituximab 17p Del. Population Venetoclax + Rituximab 17p Del. Population
Hide Arm/Group Description:
Participants received bendamustine at a dose of 70 mg/m^2 via IV infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6. Only participants with 17p deletion as identified by FISH test were included.
Participants were initially placed on a venetoclax ramp-up period of 4 to 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6. Only participants with 17p deletion as identified by FISH test were included.
Overall Number of Participants Analyzed 46 46
Measure Type: Number
Unit of Measure: percentage of participants
47.8 19.6
8.Secondary Outcome
Title PFS as Assessed by the IRC Using Standard iwCLL Guidelines in Participants With 17p Deletion as Identified by FISH Test
Hide Description PFS was defined as the time from randomization until first occurrence of PD/relapse as assessed by the IRC using iwCLL guidelines, or death from any cause, whichever occurred first. PD: occurrence of one of the following: new lesion; new palpable lymph node (>1.5 cm); unequivocal progression of non-target lesion; increase of >/=50% in splenomegaly, hepatomegaly, blood lymphocytes with count >/=5000/mcL, longest diameter of any lesion; transformation to more aggressive histology; decrease of >/=50% in platelet or neutrophil count, or hemoglobin level by >2 g/dL or to <10 g/dL. Participants who had not progressed, relapsed, or died at the time of analysis, were censored on the date of last assessment. In case of no disease assessment after baseline, PFS was censored at the time of randomization+1 day. The median PFS was estimated using Kaplan-Meier method and the 95% CI was computed using method of Brookmeyer and Crowley.
Time Frame Baseline up to PD or death, whichever occurred first (up to approximately 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population participants with 17p deletion as identified by FISH test.
Arm/Group Title Bendamustine + Rituximab 17p Del. Population Venetoclax + Rituximab 17p Del. Population
Hide Arm/Group Description:
Participants received bendamustine at a dose of 70 mg/m^2 via IV infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6. Only participants with 17p deletion as identified by FISH test were included.
Participants were initially placed on a venetoclax ramp-up period of 4 to 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6. Only participants with 17p deletion as identified by FISH test were included.
Overall Number of Participants Analyzed 46 46
Median (95% Confidence Interval)
Unit of Measure: months
16.1
(13.6 to 22.3)
NA [1] 
(27.6 to NA)
[1]
Median and Upper Limit of 95% CI could not be estimated due to low number of participants with an event.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bendamustine + Rituximab 17p Del. Population, Venetoclax + Rituximab 17p Del. Population
Comments Stratified Analysis; Stratification factor: geographic region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.21
Confidence Interval (2-Sided) 95%
0.09 to 0.49
Estimation Comments Hazard ratio was estimated by Cox regression model.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bendamustine + Rituximab 17p Del. Population, Venetoclax + Rituximab 17p Del. Population
Comments Unstratified Analysis
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.21
Confidence Interval (2-Sided) 95%
0.09 to 0.46
Estimation Comments Hazard ratio was estimated by Cox regression model.
9.Secondary Outcome
Title Percentage of Participants With Best Overall Response of Complete Response (CR), CR With Incomplete Bone Marrow Recovery (CRi), Nodular Partial Response (nPR), or Partial Response (PR) as Assessed by the Investigator Using iwCLL Guidelines
Hide Description Response was assessed by the investigator according to the iwCLL guidelines and was confirmed by repeat assessment >/=4 weeks after initial documentation. CR: peripheral blood lymphocytes <4000/mcL; absence of any new lesion, nodal disease, lymphadenopathy, hepatomegaly, splenomegaly, and constitutional symptoms; neutrophils >1500/mcL, platelets >100000/mcL, hemoglobin >11.0 g/dL without need for transfusion or exogenous growth factors; normocellular bone marrow with <30% lymphocytes; no lymphoid nodules. CRi: fulfilling all CR criteria but persistent cytopenia. PR: >/=50% reduction in two of the following: peripheral blood lymphocytes, lymphadenopathy, spleen and/or liver enlargement; and one of the following: neutrophils >1500/mcL, platelets >100000/mcL, hemoglobin >11.0 g/dL or >/=50% improvement without need for transfusion or exogenous growth factors. nPR: fulfilling all CR criteria but presence of lymphoid nodules. The 95% CI was computed using Pearson-Clopper method.
Time Frame Baseline up to last follow-up visit (FUV) (maximum up to data cut-off date, overall approximately 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population. Participants without post-baseline response assessment were considered as non-responders.
Arm/Group Title Bendamustine + Rituximab Venetoclax + Rituximab
Hide Arm/Group Description:
Participants received bendamustine at a dose of 70 mg/m^2 via IV infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Participants were initially placed on a venetoclax ramp-up period of 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Overall Number of Participants Analyzed 195 194
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
67.7
(60.64 to 74.20)
93.3
(88.81 to 96.38)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bendamustine + Rituximab, Venetoclax + Rituximab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value 25.61
Confidence Interval (2-Sided) 95%
17.88 to 33.33
Estimation Comments The 95% CI was computed using Anderson-Hauck method.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bendamustine + Rituximab, Venetoclax + Rituximab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 7.81
Confidence Interval (2-Sided) 95%
3.97 to 15.37
Estimation Comments OR was estimated using logistic regression model. The 95% CI was computed using Wald test.
10.Secondary Outcome
Title Percentage of Participants With Best Overall Response of CR, CRi, nPR, or PR as Assessed by the IRC Using iwCLL Guidelines
Hide Description Response was assessed by the IRC according to the iwCLL guidelines and was confirmed by repeat assessment >/=4 weeks after initial documentation. CR: peripheral blood lymphocytes <4000/mcL; absence of any new lesion, nodal disease, lymphadenopathy, hepatomegaly, splenomegaly, and constitutional symptoms; neutrophils >1500/mcL, platelets >100000/mcL, hemoglobin >11.0 g/dL without need for transfusion or exogenous growth factors; normocellular bone marrow with <30% lymphocytes; no lymphoid nodules. CRi: fulfilling all CR criteria but persistent cytopenia. PR: >/=50% reduction in two of the following: peripheral blood lymphocytes, lymphadenopathy, spleen and/or liver enlargement; and one of the following: neutrophils >1500/mcL, platelets >100000/mcL, hemoglobin >11.0 g/dL or >/=50% improvement without need for transfusion or exogenous growth factors. nPR: fulfilling all CR criteria but presence of lymphoid nodules. The 95% CI was computed using Pearson-Clopper method.
Time Frame Baseline up to last FUV (maximum up to data cut-off date, overall approximately 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population. Participants without post-baseline response assessment were considered as non-responders.
Arm/Group Title Bendamustine + Rituximab Venetoclax + Rituximab
Hide Arm/Group Description:
Participants received bendamustine at a dose of 70 mg/m^2 via IV infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Participants were initially placed on a venetoclax ramp-up period of 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Overall Number of Participants Analyzed 195 194
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
72.3
(65.46 to 78.46)
92.3
(87.57 to 95.61)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bendamustine + Rituximab, Venetoclax + Rituximab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value 19.96
Confidence Interval (2-Sided) 95%
12.36 to 27.56
Estimation Comments The 95% CI was computed using Anderson-Hauck method.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bendamustine + Rituximab, Venetoclax + Rituximab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.79
Confidence Interval (2-Sided) 95%
2.56 to 8.99
Estimation Comments OR was estimated using logistic regression model. The 95% CI was computed using Wald test.
11.Secondary Outcome
Title Percentage of Participants With Overall Response of CR, Cri, nPR, or PR at End of Combination Treatment Visit as Assessed by the Investigator Using iwCLL Guidelines
Hide Description Response was assessed by the investigator according to the iwCLL guidelines and was confirmed by repeat assessment >/=4 weeks after initial documentation. CR: peripheral blood lymphocytes <4000/mcL; absence of any new lesion, nodal disease, lymphadenopathy, hepatomegaly, splenomegaly, and constitutional symptoms; neutrophils >1500/mcL, platelets >100000/mcL, hemoglobin >11.0 g/dL without need for transfusion or exogenous growth factors; normocellular bone marrow with <30% lymphocytes; no lymphoid nodules. CRi: fulfilling all CR criteria but persistent cytopenia. PR: >/=50% reduction in two of the following: peripheral blood lymphocytes, lymphadenopathy, spleen and/or liver enlargement; and one of the following: neutrophils >1500/mcL, platelets >100000/mcL, hemoglobin >11.0 g/dL or >/=50% improvement without need for transfusion or exogenous growth factors. nPR: fulfilling all CR criteria but presence of lymphoid nodules. The 95% CI was computed using Pearson-Clopper method.
Time Frame End of combination treatment response (EoCTR) visit (8 to 12 weeks after Cycle [C] 6 Day [1]); Cycle length = 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population. Participants without post-baseline response assessment were considered as non-responders.
Arm/Group Title Bendamustine + Rituximab Venetoclax + Rituximab
Hide Arm/Group Description:
Participants received bendamustine at a dose of 70 mg/m^2 via IV infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Participants were initially placed on a venetoclax ramp-up period of 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Overall Number of Participants Analyzed 195 194
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
62.6
(55.37 to 69.37)
88.1
(82.74 to 92.33)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bendamustine + Rituximab, Venetoclax + Rituximab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value 25.58
Confidence Interval (2-Sided) 95%
17.13 to 34.03
Estimation Comments The 95% CI was computed using Anderson-Hauck method.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bendamustine + Rituximab, Venetoclax + Rituximab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.75
Confidence Interval (2-Sided) 95%
2.76 to 8.16
Estimation Comments OR was estimated using logistic regression model. The 95% CI was computed using Wald test.
12.Secondary Outcome
Title Percentage of Participants With Overall Response of CR, Cri, nPR, or PR at End of Combination Treatment Visit as Assessed by the IRC Using iwCLL Guidelines
Hide Description Response was assessed by the IRC according to the iwCLL guidelines and was confirmed by repeat assessment >/=4 weeks after initial documentation. CR: peripheral blood lymphocytes <4000/mcL; absence of any new lesion, nodal disease, lymphadenopathy, hepatomegaly, splenomegaly, and constitutional symptoms; neutrophils >1500/mcL, platelets >100000/mcL, hemoglobin >11.0 g/dL without need for transfusion or exogenous growth factors; normocellular bone marrow with <30% lymphocytes; no lymphoid nodules. CRi: fulfilling all CR criteria but persistent cytopenia. PR: >/=50% reduction in two of the following: peripheral blood lymphocytes, lymphadenopathy, spleen and/or liver enlargement; and one of the following: neutrophils >1500/mcL, platelets >100000/mcL, hemoglobin >11.0 g/dL or >/=50% improvement without need for transfusion or exogenous growth factors. nPR: fulfilling all CR criteria but presence of lymphoid nodules. The 95% CI was computed using Pearson-Clopper method.
Time Frame EoCTR visit (8 to 12 weeks after C6D1); Cycle length = 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population. Participants without post-baseline response assessment were considered as non-responders.
Arm/Group Title Bendamustine + Rituximab Venetoclax + Rituximab
Hide Arm/Group Description:
Participants received bendamustine at a dose of 70 mg/m^2 via IV infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Participants were initially placed on a venetoclax ramp-up period of 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Overall Number of Participants Analyzed 195 194
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
62.6
(55.37 to 69.37)
87.1
(81.57 to 91.48)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bendamustine + Rituximab, Venetoclax + Rituximab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value 24.55
Confidence Interval (2-Sided) 95%
16.00 to 33.10
Estimation Comments The 95% CI was computed using Anderson-Hauck method.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bendamustine + Rituximab, Venetoclax + Rituximab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.59
Confidence Interval (2-Sided) 95%
2.68 to 7.85
Estimation Comments OR was estimated using logistic regression model. The 95% CI was computed using Wald test.
13.Secondary Outcome
Title Percentage of Participants Who Died
Hide Description Percentage of participants who died from any cause, during the study, was reported.
Time Frame Baseline up to last FUV (maximum up to Data Cut-off date, overall approximately 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population.
Arm/Group Title Bendamustine + Rituximab Venetoclax + Rituximab
Hide Arm/Group Description:
Participants received bendamustine at a dose of 70 mg/m^2 via IV infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Participants were initially placed on a venetoclax ramp-up period of 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Overall Number of Participants Analyzed 195 194
Measure Type: Number
Unit of Measure: percentage of participants
13.8 7.7
14.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time from the date of randomization to the date of death from any cause. Participants alive at the time of the analysis were censored at the date when they were last known to be alive as documented by the investigator. The median OS was estimated using Kaplan-Meier method and the 95% CI was computed using method of Brookmeyer and Crowley.
Time Frame Baseline up to last FUV (maximum up to Data Cut-off date, overall approximately 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population.
Arm/Group Title Bendamustine + Rituximab Venetoclax + Rituximab
Hide Arm/Group Description:
Participants received bendamustine at a dose of 70 mg/m^2 via IV infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Participants were initially placed on a venetoclax ramp-up period of 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Overall Number of Participants Analyzed 195 194
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Median and corresponding 95% CI could not be estimated due to low number of participants with an event.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bendamustine + Rituximab, Venetoclax + Rituximab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Stratified Analysis; Stratification factors: 17p deletion, risk status, geographic region.
Statistical Test of Hypothesis P-Value 0.0186
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.48
Confidence Interval (2-Sided) 95%
0.25 to 0.90
Estimation Comments Hazard ratio was estimated by Cox regression model.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bendamustine + Rituximab, Venetoclax + Rituximab
Comments Unstratified Analysis
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0190
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.48
Confidence Interval (2-Sided) 95%
0.25 to 0.90
Estimation Comments Hazard ratio was estimated by Cox regression model.
15.Secondary Outcome
Title Percentage of Participants With PD/Relapse, Start of a New Anti-Chronic Lymphocytic Leukemia (CLL) Therapy, or Death as Assessed by the Investigator Using iwCLL Guidelines
Hide Description Percentage of participants with PD/relapse, death from any cause, or start of a new non-protocol-specified anti-CLL therapy as assessed by the investigator, during the study, was reported. PD was defined as occurrence of one of the following events: appearance of any new extra nodal lesion; new palpable lymph node (>1.5 cm); unequivocal progression of non-target lesion; an increase of >/=50% compared to baseline in splenomegaly, hepatomegaly, number of blood lymphocytes with lymphocyte count >/=5000/mcL, or in longest diameter of any extra nodal lesion; transformation to a more aggressive histology; decrease of >/=50% compared to baseline in platelet or neutrophil count; or decrease in hemoglobin level by >2 g/dL or to <10 g/dL.
Time Frame Baseline up to PD/relapse, start of a new anti-CLL therapy, or death from any cause, whichever occurred first (maximum up to Data Cut-off date, overall approximately 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population.
Arm/Group Title Bendamustine + Rituximab Venetoclax + Rituximab
Hide Arm/Group Description:
Participants received bendamustine at a dose of 70 mg/m^2 via IV infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Participants were initially placed on a venetoclax ramp-up period of 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Overall Number of Participants Analyzed 195 194
Measure Type: Number
Unit of Measure: percentage of participants
60.5 17.0
16.Secondary Outcome
Title Event-Free Survival (EFS) as Assessed by the Investigator Using iwCLL Guidelines
Hide Description EFS was defined as the time from date of randomization until the date of PD/relapse, start of a new non-protocol-specified anti-CLL therapy, or death from any cause, whichever occurred first, as assessed by the investigator. PD: occurrence of one of the following: new lesion; new palpable lymph node (>1.5 cm); unequivocal progression of non-target lesion; increase of >/=50% in splenomegaly, hepatomegaly, blood lymphocytes with count >/=5000/mcL, longest diameter of any lesion; transformation to more aggressive histology; decrease of >/=50% in platelet or neutrophil count, or hemoglobin level by >2 g/dL or to <10 g/dL. Participants without any of the specified event at the time of analysis were censored at the date of last adequate response assessment. In case of no post-baseline response assessment, participants were censored at the randomization date. The median EFS was estimated using Kaplan-Meier method and the 95% CI was computed using method of Brookmeyer and Crowley.
Time Frame Baseline up to PD/relapse, start of a new anti-CLL therapy, or death from any cause, whichever occurred first (maximum up to Data Cut-off date, overall approximately 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population.
Arm/Group Title Bendamustine + Rituximab Venetoclax + Rituximab
Hide Arm/Group Description:
Participants received bendamustine at a dose of 70 mg/m^2 via IV infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Participants were initially placed on a venetoclax ramp-up period of 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Overall Number of Participants Analyzed 195 194
Median (95% Confidence Interval)
Unit of Measure: months
16.4
(14.6 to 21.2)
NA [1] 
(NA to NA)
[1]
Median and corresponding 95% CI could not be estimated due to low number of participants with an event.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bendamustine + Rituximab, Venetoclax + Rituximab
Comments Stratified Analysis; Stratification factors: 17p deletion, risk status, geographic region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.17
Confidence Interval (2-Sided) 95%
0.11 to 0.25
Estimation Comments Hazard ratio was estimated by Cox regression model.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bendamustine + Rituximab, Venetoclax + Rituximab
Comments Unstratified Analysis
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.18
Confidence Interval (2-Sided) 95%
0.12 to 0.26
Estimation Comments Hazard ratio was estimated by Cox regression model.
17.Secondary Outcome
Title Percentage of Participants With PD or Death Among Participants With Best Overall Response of CR, CRi, nPR, or PR as Assessed by the Investigator Using iwCLL Guidelines
Hide Description Percentage of participants with PD as assessed by the investigator according to the iwCLL guidelines or death from any cause during the study was reported. PD was defined as occurrence of one of the following events: appearance of any new extra nodal lesion; new palpable lymph node (>1.5 cm); unequivocal progression of non-target lesion; an increase of >/=50% compared to baseline in splenomegaly, hepatomegaly, number of blood lymphocytes with lymphocyte count >/=5000/mcL, or in longest diameter of any extra nodal lesion; transformation to a more aggressive histology; decrease of >/=50% compared to baseline in platelet or neutrophil count; or decrease in hemoglobin level by >2 g/dL or to <10 g/dL. CR, CRi, nPR, and PR have been defined in previous outcomes, and are not repeated here due to space constraint.
Time Frame From time of achieving best overall response until PD or death from any cause, whichever occurred first (up to approximately 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population participants who had best overall response of CR, CRi, nPR, or PR.
Arm/Group Title Bendamustine + Rituximab Venetoclax + Rituximab
Hide Arm/Group Description:
Participants received bendamustine at a dose of 70 mg/m^2 via IV infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Participants were initially placed on a venetoclax ramp-up period of 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Overall Number of Participants Analyzed 132 181
Measure Type: Number
Unit of Measure: percentage of participants
53.8 11.0
18.Secondary Outcome
Title Duration of Responses (DOR) as Assessed by the Investigator Using iwCLL Guidelines
Hide Description DOR was defined as the time from first occurrence of a documented response of CR, CRi, nPR, or PR until PD/relapse, as assessed by the investigator according to the iwCLL guidelines, or death from any cause. PD: occurrence of one of the following: new lesion; new palpable lymph node (>1.5 cm); unequivocal progression of non-target lesion; increase of >/=50% in splenomegaly, hepatomegaly, blood lymphocytes with count >/=5000/mcL, longest diameter of any lesion; transformation to more aggressive histology; decrease of >/=50% in platelet or neutrophil count, or hemoglobin level by >2 g/dL or to <10 g/dL. Participants without PD or death after response were censored at the last date of adequate response assessment. The median DOR was estimated using Kaplan-Meier method and the 95% CI was computed using method of Brookmeyer and Crowley. CR, CRi, nPR, and PR have been defined in previous outcomes, and are not repeated here due to space constraint.
Time Frame From time of achieving best overall response until PD or death from any cause, whichever occurred first (up to approximately 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population participants who had best overall response of CR, CRi, nPR, or PR.
Arm/Group Title Bendamustine + Rituximab Venetoclax + Rituximab
Hide Arm/Group Description:
Participants received bendamustine at a dose of 70 mg/m^2 via IV infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Participants were initially placed on a venetoclax ramp-up period of 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Overall Number of Participants Analyzed 132 181
Median (95% Confidence Interval)
Unit of Measure: months
19.4
(16.1 to 22.6)
NA [1] 
(NA to NA)
[1]
Median and corresponding 95% CI could not be estimated due to low number of participants with an event.
19.Secondary Outcome
Title Percentage of Participants With Start of New Anti-CLL Treatment or Death as Assessed by the Investigator
Hide Description Percentage of participants with start of new non-protocol-specified anti-CLL therapy, as assessed by the investigator, or death from any cause, during the study, was reported.
Time Frame Baseline up to start of new ani-CLL therapy or death, whichever occurred first (up to approximately 3 years)
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Hide Analysis Population Description
Analysis was performed on ITT population.
Arm/Group Title Bendamustine + Rituximab Venetoclax + Rituximab
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Participants received bendamustine at a dose of 70 mg/m^2 via IV infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Participants were initially placed on a venetoclax ramp-up period of 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Overall Number of Participants Analyzed 195 194
Measure Type: Number
Unit of Measure: percentage of participants
42.6 11.9
20.Secondary Outcome
Title Time to New Anti-CLL Treatment (TTNT) as Assessed by the Investigator
Hide Description TTNT was defined as the time from randomization until start of new non-protocol-specified anti-CLL treatment or death from any cause. Participants without the event at the time of analysis were censored at the last visit date for this outcome measure analysis. The median TTNT was estimated using Kaplan-Meier method and the 95% CI was computed using method of Brookmeyer and Crowley.
Time Frame Baseline up to start of new ani-CLL therapy or death, whichever occurred first (up to approximately 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on ITT population.
Arm/Group Title Bendamustine + Rituximab Venetoclax + Rituximab
Hide Arm/Group Description:
Participants received bendamustine at a dose of 70 mg/m^2 via IV infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Participants were initially placed on a venetoclax ramp-up period of 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Overall Number of Participants Analyzed 195 194
Median (95% Confidence Interval)
Unit of Measure: months
26.4
(21.9 to 33.1)
NA [1] 
(NA to NA)
[1]
Median and corresponding 95% CI could not be estimated due to low number of participants with an event.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bendamustine + Rituximab, Venetoclax + Rituximab
Comments Stratified Analysis; Stratification factors: 17p deletion, risk status, geographic region.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.19
Confidence Interval (2-Sided) 95%
0.12 to 0.31
Estimation Comments Hazard ratio was estimated by Cox regression model.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bendamustine + Rituximab, Venetoclax + Rituximab
Comments Unstratified Analysis
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.19
Confidence Interval (2-Sided) 95%
0.12 to 0.31
Estimation Comments Hazard ratio was estimated by Cox regression model.
21.Secondary Outcome
Title Percentage of Participants With Minimal Residual Disease (MRD) Negativity at the EoCTR Visit
Hide Description MRD-negativity was defined as the presence of <1 malignant B-cell per 10000 normal B-cells in a sample of at least 200000 B-cells, as assessed by the allele specific oligonucleotide polymerase chain reaction (ASO-PCR) and/or flow cytometry technique. Percentage of participants with MRD-negativity at the EoCTR visit was reported. The 95% CI was computed using Pearson-Clopper method.
Time Frame EoCTR visit (8 to 12 weeks after C6D1); Cycle length = 28 days
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Hide Analysis Population Description
Analysis was performed on ITT population.
Arm/Group Title Bendamustine + Rituximab Venetoclax + Rituximab
Hide Arm/Group Description:
Participants received bendamustine at a dose of 70 mg/m^2 via IV infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Participants were initially placed on a venetoclax ramp-up period of 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Overall Number of Participants Analyzed 195 194
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
13.3
(8.90 to 18.92)
62.4
(55.15 to 69.21)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bendamustine + Rituximab, Venetoclax + Rituximab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in MRD Negativity Rates
Estimated Value 49.04
Confidence Interval (2-Sided) 95%
40.44 to 57.64
Estimation Comments The 95% CI was computed using Anderson-Hauck method.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bendamustine + Rituximab, Venetoclax + Rituximab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 10.77
Confidence Interval (2-Sided) 95%
6.50 to 17.85
Estimation Comments OR was estimated using logistic regression model. The 95% CI was computed using Wald test.
22.Secondary Outcome
Title Plasma Venetoclax Concentrations
Hide Description [Not Specified]
Time Frame Pre-dose (0 hour, anytime before venetoclax administeration) and 4 hours post-dose on D1 of Cycles 1 and 4; Cycle length = 28 days
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Hide Analysis Population Description
Analysis was performed on Pharmacokinetic (PK)-Evaluable population, which included all participants in the ‘Venetoclax + Rituximab’ arm and who received at least one dose of venetoclax with at least one post-dose PK concentration result available. Here 'Number Analyzed' signifies the number of participants evaluable at specified time point.
Arm/Group Title Venetoclax + Rituximab
Hide Arm/Group Description:
Participants were initially placed on a venetoclax ramp-up period of 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Overall Number of Participants Analyzed 184
Mean (Standard Deviation)
Unit of Measure: micrograms per milliliter (mcg/mL)
C1D1, Pre-dose Number Analyzed 151 participants
0.626  (0.540)
C1D1, 4 hours Post-Dose Number Analyzed 159 participants
1.34  (0.881)
C4D1, Pre-dose Number Analyzed 112 participants
0.681  (0.745)
C4D1, 4 hours Post-Dose Number Analyzed 121 participants
1.34  (0.905)
23.Secondary Outcome
Title Change From Baseline in Lymphocyte Subset Counts at Specified Time Points
Hide Description [Not Specified]
Time Frame Baseline, C4D14-28, Study Treatment Completion/Early Withdrawal (STC/EW, up to C6D28), EoCTR visit (8 to 12 weeks after C6D1), and at FUVs (every 12 weeks after EoCTR up to 3 years); Cycle length = 28 days
Outcome Measure Data Not Reported
24.Secondary Outcome
Title Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Core Symptom Severity, Module Symptom Severity, and Interference Scores
Hide Description MDASI is a 25-item validated questionnaire consisting of 2 parts. Part 1: 19-items divided into 2 scales, Core Symptom Severity (average of Questions 1 to 13; total 13 items: pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, remembering things, lack of appetite, drowsiness, dry mouth, sadness, vomiting, and numbness) and Module Symptom Severity (average of Questions 14 to 19; total 6 items: night sweats, fevers and chills, lymph node swelling, diarrhea, bruising easy or bleeding, and constipation). Part 2: 6-items to assess Interference (symptom distress) (average of Questions 20 to 25; total 6 items: general activity, walking, work, mood, relations with other people, and enjoyment of life). Each item was rated from 0 to 10, with lower scores indicating better outcome. Total score for Core Symptom Severity, Module Symptom Severity, and Interference are reported which range from 0 to 10, with lower scores indicating better health-related quality of life (HRQoL).
Time Frame Baseline, Days 1, 8, and 15 of Cycles 1, 2, and 3; Cycle length = 28 days
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Hide Analysis Population Description
Analysis was performed on patient reported outcome (PRO)-evaluable population, which included all participants with baseline and at least one post-baseline PRO assessment. Here, 'Overall Number of Participants Analyzed’ = participants evaluable for this outcome measure and 'Number Analyzed' = participants evaluable at specified time point.
Arm/Group Title Bendamustine + Rituximab Venetoclax + Rituximab
Hide Arm/Group Description:
Participants received bendamustine at a dose of 70 mg/m^2 via IV infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Participants were initially placed on a venetoclax ramp-up period of 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Overall Number of Participants Analyzed 117 42
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline; Mean core symptom severity Number Analyzed 116 participants 42 participants
1.76  (1.55) 1.55  (1.31)
Change at C1D1; Mean core symptom severity Number Analyzed 116 participants 36 participants
0.00  (0.00) -0.08  (0.98)
Change at C1D8; Mean core symptom severity Number Analyzed 107 participants 36 participants
0.26  (1.34) -0.30  (0.84)
Change at C1D15; Mean core symptom severity Number Analyzed 104 participants 33 participants
0.00  (1.31) -0.27  (0.93)
Change at C2D1; Mean core symptom severity Number Analyzed 101 participants 35 participants
-0.23  (1.30) -0.33  (0.91)
Change at C2D8; Mean core symptom severity Number Analyzed 91 participants 36 participants
0.17  (1.59) -0.45  (0.91)
Change at C2D15; Mean core symptom severity Number Analyzed 90 participants 37 participants
-0.13  (1.53) -0.53  (0.90)
Change at C3D1; Mean core symptom severity Number Analyzed 89 participants 36 participants
-0.26  (1.60) -0.40  (1.13)
Change at C3D8; Mean core symptom severity Number Analyzed 72 participants 30 participants
-0.13  (1.63) -0.66  (1.20)
Change at C3D15; Mean core symptom severity Number Analyzed 73 participants 32 participants
-0.42  (1.52) -0.53  (1.05)
Baseline; Mean module symptom severity Number Analyzed 116 participants 42 participants
1.60  (1.46) 1.57  (1.11)
Change at C1D1; Mean module symptom severity Number Analyzed 116 participants 36 participants
0.00  (0.00) -0.19  (0.96)
Change at C1D8; Mean module symptom severity Number Analyzed 107 participants 36 participants
-0.22  (1.40) -0.53  (0.96)
Change at C1D15; Mean module symptom severity Number Analyzed 104 participants 33 participants
-0.43  (1.51) -0.73  (1.13)
Change at C2D1; Mean module symptom severity Number Analyzed 101 participants 34 participants
-0.49  (1.46) -0.65  (0.92)
Change at C2D8; Mean module symptom severity Number Analyzed 91 participants 35 participants
-0.46  (1.63) -0.77  (0.87)
Change at C2D15; Mean module symptom severity Number Analyzed 90 participants 36 participants
-0.69  (1.47) -0.94  (0.93)
Change at C3D1; Mean module symptom severity Number Analyzed 86 participants 35 participants
-0.65  (1.48) -0.81  (0.97)
Change at C3D8; Mean module symptom severity Number Analyzed 72 participants 30 participants
-0.51  (1.58) -0.83  (0.97)
Change at C3D15; Mean module symptom severity Number Analyzed 73 participants 32 participants
-0.83  (1.51) -0.92  (0.97)
Baseline; Mean interference Number Analyzed 116 participants 41 participants
1.81  (2.05) 1.90  (2.25)
Change at C1D1; Mean interference Number Analyzed 116 participants 35 participants
0.00  (0.00) -0.13  (1.49)
Change at C1D8; Mean interference Number Analyzed 107 participants 33 participants
0.45  (1.78) -0.29  (2.14)
Change at C1D15; Mean interference Number Analyzed 104 participants 32 participants
0.36  (1.85) 0.01  (2.04)
Change at C2D1; Mean interference Number Analyzed 101 participants 33 participants
0.01  (1.73) -0.34  (1.78)
Change at C2D8; Mean interference Number Analyzed 91 participants 34 participants
0.58  (2.20) -0.58  (1.81)
Change at C2D15; Mean interference Number Analyzed 89 participants 35 participants
0.06  (1.84) -0.64  (1.59)
Change at C3D1; Mean interference Number Analyzed 86 participants 34 participants
-0.02  (2.02) -0.73  (2.06)
Change at C3D8; Mean interference Number Analyzed 72 participants 29 participants
0.15  (1.91) -0.82  (2.09)
Change at C3D15; Mean interference Number Analyzed 72 participants 30 participants
-0.07  (2.01) -0.55  (2.18)
25.Secondary Outcome
Title Change From Baseline in HRQoL as Measured by European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) Functional Scales Score and Global Health Status/Global Quality-of-Life (QoL) Scale Score
Hide Description The EORTC QLQ-C30 is a validated self-report measure consisting of 30 questions incorporated into five functional scales (Physical, Role, Cognitive, Emotional, and Social scales), three symptom scales (fatigue, pain, nausea, and vomiting scales), a global health status/global QoL scale, and single items (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea). Most questions used 4-point scale (1='Not at all' to 4='Very much'), while 2 questions used 7-point scale (1='very poor' to 7='Excellent'). Functional scales score and global health status/global QoL scale score are reported. Scores were averaged, transformed to 0-100 scale; where higher score for functional scales = poor level of functioning and higher score for global health status/global QoL = better HRQoL.
Time Frame Baseline, D1 of Cycles 1, 2, 3, 4, 5, 6, STC/EW visit (up to C6D28), EoCTR visit (8 to 12 weeks after C6D1), and FUVs (every 12 weeks after EoCTR up to 3 years); Cycle length = 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PRO-evaluable population. Here, 'Overall Number of Participants Analyzed’ signifies the number of participants evaluable for this outcome measure and 'Number Analyzed' signifies the number of participants evaluable at specified time point.
Arm/Group Title Bendamustine + Rituximab Venetoclax + Rituximab
Hide Arm/Group Description:
Participants received bendamustine at a dose of 70 mg/m^2 via IV infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Participants were initially placed on a venetoclax ramp-up period of 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Overall Number of Participants Analyzed 177 69
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline; Physical functioning Number Analyzed 177 participants 69 participants
82.59  (17.46) 83.77  (15.27)
Change at C1D1; Physical functioning Number Analyzed 177 participants 67 participants
0.0  (0.0) 1.39  (12.90)
Change at C2D1; Physical functioning Number Analyzed 172 participants 67 participants
0.31  (15.81) 2.99  (12.83)
Change at C3D1; Physical functioning Number Analyzed 160 participants 64 participants
0.22  (16.43) 1.46  (14.76)
Change at C4D1; Physical functioning Number Analyzed 154 participants 65 participants
2.11  (14.95) 5.54  (14.17)
Change at C5D1; Physical functioning Number Analyzed 149 participants 65 participants
2.44  (18.19) 4.62  (15.27)
Change at C6D1; Physical functioning Number Analyzed 143 participants 65 participants
2.25  (16.82) 4.51  (16.59)
Change at STC/EW; Physical functioning Number Analyzed 162 participants 64 participants
1.68  (18.76) 4.53  (16.04)
Change at EoCTR; Physical functioning Number Analyzed 142 participants 63 participants
2.92  (18.03) 4.34  (16.12)
Change at FUV1; Physical functioning Number Analyzed 124 participants 63 participants
2.27  (18.86) 3.81  (16.27)
Change at FUV2; Physical functioning Number Analyzed 114 participants 63 participants
2.40  (19.21) 2.75  (17.17)
Change at FUV3; Physical functioning Number Analyzed 95 participants 62 participants
2.54  (17.83) 3.44  (17.31)
Change at FUV4; Physical functioning Number Analyzed 77 participants 47 participants
4.74  (20.14) 0.85  (21.06)
Change at FUV5; Physical functioning Number Analyzed 57 participants 19 participants
1.90  (17.68) -1.75  (19.35)
Change at FUV6; Physical functioning Number Analyzed 33 participants 5 participants
-1.41  (15.34) 1.33  (5.58)
Change at FUV7; Physical functioning Number Analyzed 13 participants 1 participants
-3.08  (11.74) 0.00
Change at FUV8; Physical functioning Number Analyzed 5 participants 1 participants
-9.33  (23.38) 0.00
Change at FUV9; Physical functioning Number Analyzed 2 participants 0 participants
-10.00  (33.0)
Baseline; Role functioning Number Analyzed 177 participants 69 participants
78.25  (25.67) 83.82  (21.00)
Change at C1D1; Role functioning Number Analyzed 177 participants 67 participants
0.0  (0.0) -1.74  (23.23)
Change at C2D1; Role functioning Number Analyzed 172 participants 67 participants
-1.26  (27.45) 2.49  (23.07)
Change at C3D1; Role functioning Number Analyzed 160 participants 64 participants
-0.10  (29.64) 1.82  (26.08)
Change at C4D1; Role functioning Number Analyzed 154 participants 65 participants
0.87  (29.01) 5.13  (22.03)
Change at C5D1; Role functioning Number Analyzed 149 participants 65 participants
0.45  (30.75) 4.36  (23.44)
Change at C6D1; Role functioning Number Analyzed 143 participants 65 participants
0.70  (29.92) 1.79  (25.71)
Change at STC/EW; Role functioning Number Analyzed 162 participants 64 participants
-0.41  (32.91) 2.60  (25.58)
Change at EoCTR; Role functioning Number Analyzed 143 participants 63 participants
3.26  (29.95) 2.12  (26.69)
Change at FUV1; Role functioning Number Analyzed 125 participants 63 participants
2.93  (32.31) 2.65  (27.47)
Change at FUV2; Role functioning Number Analyzed 114 participants 63 participants
3.07  (32.63) -1.85  (31.84)
Change at FUV3; Role functioning Number Analyzed 95 participants 62 participants
5.26  (31.16) 1.88  (28.17)
Change at FUV4; Role functioning Number Analyzed 77 participants 47 participants
5.41  (33.16) -0.35  (30.39)
Change at FUV5; Role functioning Number Analyzed 57 participants 19 participants
2.34  (29.79) 1.75  (34.20)
Change at FUV6; Role functioning Number Analyzed 33 participants 5 participants
-4.04  (27.01) -13.33  (32.06)
Change at FUV7; Role functioning Number Analyzed 13 participants 1 participants
2.56  (29.54) -16.67
Change at FUV8; Role functioning Number Analyzed 5 participants 1 participants
0.00  (23.57) 16.67
Change at FUV9; Role functioning Number Analyzed 2 participants 0 participants
-16.67  (23.57)
Baseline; Emotional functioning Number Analyzed 176 participants 69 participants
78.98  (22.47) 82.13  (15.80)
Change at C1D1; Emotional functioning Number Analyzed 176 participants 67 participants
0.0  (0.0) 4.35  (15.17)
Change at C2D1; Emotional functioning Number Analyzed 171 participants 67 participants
2.24  (20.07) 5.60  (14.68)
Change at C3D1; Emotional functioning Number Analyzed 158 participants 64 participants
2.99  (20.06) 5.34  (19.09)
Change at C4D1; Emotional functioning Number Analyzed 151 participants 65 participants
2.61  (18.35) 4.19  (15.45)
Change at C5D1; Emotional functioning Number Analyzed 146 participants 65 participants
1.14  (18.79) 3.97  (17.37)
Change at C6D1; Emotional functioning Number Analyzed 143 participants 65 participants
2.06  (18.74) 3.08  (17.96)
Change at STC/EW; Emotional functioning Number Analyzed 160 participants 64 participants
2.43  (20.61) 5.34  (18.69)
Change at EoCTR; Emotional functioning Number Analyzed 142 participants 62 participants
2.58  (19.45) 3.49  (17.83)
Change at FUV1; Emotional functioning Number Analyzed 124 participants 63 participants
3.49  (20.91) 4.37  (18.50)
Change at FUV2; Emotional functioning Number Analyzed 114 participants 63 participants
4.39  (20.33) 0.66  (21.02)
Change at FUV3; Emotional functioning Number Analyzed 92 participants 62 participants
0.63  (19.97) 2.82  (17.66)
Change at FUV4; Emotional functioning Number Analyzed 76 participants 47 participants
4.82  (19.73) 1.95  (18.41)
Change at FUV5; Emotional functioning Number Analyzed 56 participants 19 participants
3.13  (17.95) 2.63  (20.61)
Change at FUV6; Emotional functioning Number Analyzed 33 participants 5 participants
2.27  (21.78) 5.00  (17.28)
Change at FUV7; Emotional functioning Number Analyzed 13 participants 1 participants
5.77  (17.48) -8.33
Change at FUV8; Emotional functioning Number Analyzed 5 participants 1 participants
3.33  (28.01) 0.00
Change at FUV9; Emotional functioning Number Analyzed 2 participants 0 participants
-16.67  (11.79)
Baseline; Cognitive functioning Number Analyzed 176 participants 69 participants
86.55  (16.78) 89.86  (14.91)
Change at C1D1; Cognitive functioning Number Analyzed 176 participants 67 participants
0.0  (0.0) -1.24  (14.01)
Change at C2D1; Cognitive functioning Number Analyzed 171 participants 67 participants
-0.19  (15.34) 0.25  (14.06)
Change at C3D1; Cognitive functioning Number Analyzed 158 participants 64 participants
-0.32  (16.34) -1.56  (17.50)
Change at C4D1; Cognitive functioning Number Analyzed 152 participants 65 participants
-1.54  (17.41) -0.26  (17.05)
Change at C5D1; Cognitive functioning Number Analyzed 146 participants 65 participants
-1.94  (18.10) -0.26  (14.28)
Change at C6D1; Cognitive functioning Number Analyzed 143 participants 65 participants
-2.68  (16.97) -0.77  (15.98)
Change at STC/EW; Cognitive functioning Number Analyzed 160 participants 64 participants
-2.19  (17.65) 1.04  (18.28)
Change at EoCTR; Cognitive functioning Number Analyzed 142 participants 62 participants
-2.23  (18.11) -0.27  (16.94)
Change at FUV1; Cognitive functioning Number Analyzed 124 participants 63 participants
-2.02  (17.21) -0.26  (15.98)
Change at FUV2; Cognitive functioning Number Analyzed 114 participants 63 participants
1.32  (16.16) -2.38  (18.17)
Change at FUV3; Cognitive functioning Number Analyzed 92 participants 62 participants
-1.63  (14.84) -2.96  (18.24)
Change at FUV4; Cognitive functioning Number Analyzed 76 participants 47 participants
0.44  (17.63) -1.77  (19.11)
Change at FUV5; Cognitive functioning Number Analyzed 56 participants 19 participants
-1.49  (15.66) -6.14  (21.67)
Change at FUV6; Cognitive functioning Number Analyzed 33 participants 5 participants
-0.51  (14.72) 0.00  (0.00)
Change at FUV7; Cognitive functioning Number Analyzed 13 participants 1 participants
-1.28  (14.37) 0.00
Change at FUV8; Cognitive functioning Number Analyzed 5 participants 1 participants
0.00  (23.57) 0.00
Change at FUV9; Cognitive functioning Number Analyzed 2 participants 0 participants
16.67  (23.57)
Baseline; Social functioning Number Analyzed 176 participants 69 participants
82.48  (22.06) 85.51  (21.18)
Change at C1D1; Social functioning Number Analyzed 176 participants 67 participants
0.0  (0.0) -1.74  (19.92)
Change at C2D1; Social functioning Number Analyzed 171 participants 67 participants
-2.44  (21.44) 0.25  (18.46)
Change at C3D1; Social functioning Number Analyzed 158 participants 64 participants
-2.32  (22.61) 3.65  (25.45)
Change at C4D1; Social functioning Number Analyzed 151 participants 65 participants
-0.55  (22.15) 4.62  (20.09)
Change at C5D1; Social functioning Number Analyzed 146 participants 65 participants
-5.48  (26.49) 2.56  (20.46)
Change at C6D1; Social functioning Number Analyzed 143 participants 65 participants
-5.13  (24.80) 3.85  (24.61)
Change at STC/EW; Social functioning Number Analyzed 160 participants 64 participants
-4.06  (27.71) 1.04  (19.22)
Change at EoCTR; Social functioning Number Analyzed 142 participants 62 participants
-0.47  (24.95) 1.88  (20.49)
Change at FUV1; Social functioning Number Analyzed 124 participants 63 participants
-1.08  (26.09) 1.59  (24.27)
Change at FUV2; Social functioning Number Analyzed 114 participants 63 participants
0.58  (24.68) 1.32  (27.97)
Change at FUV3; Social functioning Number Analyzed 92 participants 62 participants
-0.91  (24.00) 1.88  (25.98)
Change at FUV4; Social functioning Number Analyzed 76 participants 47 participants
1.97  (27.35) 1.06  (32.12)
Change at FUV5; Social functioning Number Analyzed 56 participants 19 participants
1.79  (26.72) 0.00  (33.79)
Change at FUV6; Social functioning Number Analyzed 33 participants 5 participants
1.52  (29.27) 10.00  (14.91)
Change at FUV7; Social functioning Number Analyzed 13 participants 1 participants
-2.56  (23.42) 33.33
Change at FUV8; Social functioning Number Analyzed 5 participants 1 participants
-10.00  (22.36) 33.33
Change at FUV9; Social functioning Number Analyzed 2 participants 0 participants
-25.00  (35.36)
Baseline; Global health status/QoL Number Analyzed 176 participants 69 participants
63.02  (21.45) 67.39  (22.17)
Change at C1D1; Global health status/QoL Number Analyzed 176 participants 67 participants
0.0  (0.0) 6.34  (18.41)
Change at C2D1; Global health status/QoL Number Analyzed 171 participants 67 participants
2.73  (21.69) 5.35  (20.14)
Change at C3D1; Global health status/QoL Number Analyzed 157 participants 64 participants
2.34  (24.66) 2.21  (23.58)
Change at C4D1; Global health status/QoL Number Analyzed 152 participants 65 participants
3.84  (22.26) 7.05  (21.05)
Change at C5D1; Global health status/QoL Number Analyzed 146 participants 65 participants
7.36  (24.20) 7.18  (21.94)
Change at C6D1; Global health status/QoL Number Analyzed 143 participants 65 participants
4.25  (25.00) 5.90  (25.16)
Change at STC/EW; Global health status/QoL Number Analyzed 160 participants 64 participants
4.32  (26.20) 6.51  (23.22)
Change at EoCTR; Global health status/QoL Number Analyzed 142 participants 62 participants
6.10  (23.65) 7.66  (24.11)
Change at FUV1; Global health status/QoL Number Analyzed 124 participants 63 participants
5.91  (24.57) 7.01  (25.01)
Change at FUV2; Global health status/QoL Number Analyzed 114 participants 63 participants
6.94  (24.81) 4.50  (26.51)
Change at FUV3; Global health status/QoL Number Analyzed 92 participants 62 participants
4.80  (25.30) 6.32  (27.36)
Change at FUV4; Global health status/QoL Number Analyzed 76 participants 47 participants
7.35  (26.77) 6.38  (27.60)
Change at FUV5; Global health status/QoL Number Analyzed 56 participants 19 participants
4.46  (23.89) 4.39  (18.08)
Change at FUV6; Global health status/QoL Number Analyzed 33 participants 5 participants
1.01  (24.00) 5.00  (7.45)
Change at FUV7; Global health status/QoL Number Analyzed 13 participants 1 participants
8.33  (25.69) 16.67
Change at FUV8; Global health status/QoL Number Analyzed 5 participants 1 participants
6.67  (16.03) 8.33
Change at FUV9; Global health status/QoL Number Analyzed 2 participants 0 participants
0.00  (0.00)
26.Secondary Outcome
Title Change From Baseline in HRQoL as Measured by Quality of Life Questionnaire Associated CLL Module (QLQ-CLL16) Multi-Item Scales Score
Hide Description The EORTC QLQ-CLL16 module is designed for participants with Stage 0 to Stage 4 CLL. It is composed of 16 questions and there are four multi-item scales on Fatigue (2 items), Treatment-related side effects (TRSE, 4 items), Disease-related symptoms (DRS, 4 items), and Infection (4 items); and two single-item scales on social activities and future health worries. Multi-item scales score are reported and the total score for each multi-item scale was transformed to result in a total score range of 0 to 100, where higher score = poor HRQoL.
Time Frame Baseline, D1 of Cycles 1, 2, 3, 4, 5, 6, STC/EW visit (up to C6D28), EoCTR visit (8 to 12 weeks after C6D1), and FUVs (every 12 weeks after EoCTR up to 3 years); Cycle length = 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PRO-evaluable population. Here, 'Overall Number of Participants Analyzed’ signifies the number of participants evaluable for this outcome measure and 'Number Analyzed' signifies the number of participants evaluable at specified time point.
Arm/Group Title Bendamustine + Rituximab Venetoclax + Rituximab
Hide Arm/Group Description:
Participants received bendamustine at a dose of 70 mg/m^2 via IV infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Participants were initially placed on a venetoclax ramp-up period of 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Overall Number of Participants Analyzed 175 69
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline; TRSE Number Analyzed 175 participants 69 participants
14.29  (13.95) 9.42  (8.80)
Change at C1D1; TRSE Number Analyzed 175 participants 67 participants
0.0  (0.0) 0.12  (10.10)
Change at C2D1; TRSE Number Analyzed 170 participants 67 participants
1.62  (13.82) 0.62  (12.76)
Change at C3D1; TRSE Number Analyzed 159 participants 63 participants
-0.26  (13.76) 1.98  (14.72)
Change at C4D1; TRSE Number Analyzed 152 participants 64 participants
-0.49  (13.97) 0.52  (11.87)
Change at C5D1; TRSE Number Analyzed 147 participants 65 participants
-0.51  (14.57) 0.64  (10.02)
Change at C6D1; TRSE Number Analyzed 144 participants 65 participants
0.46  (15.51) -0.13  (10.04)
Change at STC/EW; TRSE Number Analyzed 161 participants 64 participants
0.81  (18.11) 0.13  (10.76)
Change at EoCTR; TRSE Number Analyzed 142 participants 63 participants
-0.88  (16.06) 0.26  (12.61)
Change at FUV1; TRSE Number Analyzed 123 participants 63 participants
-1.20  (14.87) 1.19  (12.24)
Change at FUV2; TRSE Number Analyzed 113 participants 63 participants
-1.70  (15.28) 2.65  (14.03)
Change at FUV3; TRSE Number Analyzed 95 participants 62 participants
-2.08  (12.64) -0.13  (13.70)
Change at FUV4; TRSE Number Analyzed 76 participants 47 participants
-1.97  (12.76) 2.84  (15.18)
Change at FUV5; TRSE Number Analyzed 56 participants 19 participants
-2.68  (11.02) 1.32  (10.49)
Change at FUV6; TRSE Number Analyzed 33 participants 5 participants
-1.01  (12.10) -1.67  (3.73)
Change at FUV7; TRSE Number Analyzed 13 participants 1 participants
2.56  (22.67) -8.33
Change at FUV8; TRSE Number Analyzed 5 participants 1 participants
1.67  (13.69) 0.00
Change at FUV9; TRSE Number Analyzed 2 participants 0 participants
8.33  (11.79)
Baseline; DRS Number Analyzed 175 participants 69 participants
19.57  (16.81) 16.95  (17.37)
Change at C1D1; DRS Number Analyzed 175 participants 67 participants
0.0  (0.0) -2.74  (16.18)
Change at C2D1; DRS Number Analyzed 170 participants 67 participants
-3.33  (16.05) -4.77  (16.84)
Change at C3D1; DRS Number Analyzed 159 participants 63 participants
-4.77  (16.49) -3.35  (17.48)
Change at C4D1; DRS Number Analyzed 152 participants 64 participants
-6.03  (16.51) -5.12  (17.72)
Change at C5D1; DRS Number Analyzed 147 participants 65 participants
-5.90  (16.73) -4.79  (17.50)
Change at C6D1; DRS Number Analyzed 144 participants 65 participants
-6.40  (17.26) -5.30  (16.72)
Change at STC/EW; DRS Number Analyzed 161 participants 64 participants
-5.80  (18.52) -6.51  (18.45)
Change at EoCTR; DRS Number Analyzed 142 participants 63 participants
-6.57  (17.21) -5.86  (20.38)
Change at FUV1; DRS Number Analyzed 123 participants 63 participants
-6.55  (15.73) -5.82  (19.20)
Change at FUV2; DRS Number Analyzed 113 participants 63 participants
-8.63  (14.39) -3.57  (18.31)
Change at FUV3; DRS Number Analyzed 95 participants 62 participants
-7.37  (14.88) -3.76  (19.25)
Change at FUV4; DRS Number Analyzed 76 participants 47 participants
-8.55  (18.56) -2.66  (20.49)
Change at FUV5; DRS Number Analyzed 56 participants 19 participants
-8.33  (16.13) -2.19  (19.41)
Change at FUV6; DRS Number Analyzed 33 participants 5 participants
-6.31  (16.01) -3.33  (13.94)
Change at FUV7; DRS Number Analyzed 13 participants 1 participants
-15.38  (20.08) -8.33
Change at FUV8; DRS Number Analyzed 5 participants 1 participants
-10.00  (16.03) -8.33
Change at FUV9; DRS Number Analyzed 2 participants 0 participants
-4.17  (5.89)
Baseline; Fatigue Number Analyzed 175 participants 69 participants
28.76  (24.66) 21.74  (20.67)
Change at C1D1; Fatigue Number Analyzed 175 participants 67 participants
0.0  (0.0) -2.24  (20.29)
Change at C2D1; Fatigue Number Analyzed 170 participants 67 participants
-2.55  (22.86) -5.47  (21.40)
Change at C3D1; Fatigue Number Analyzed 159 participants 63 participants
-2.83  (25.17) -3.17  (23.73)
Change at C4D1; Fatigue Number Analyzed 152 participants 64 participants
-3.18  (23.23) -4.17  (22.02)
Change at C5D1; Fatigue Number Analyzed 147 participants 65 participants
-2.38  (27.52) -4.36  (20.89)
Change at C6D1; Fatigue Number Analyzed 144 participants 65 participants
-2.66  (26.35) -2.31  (21.42)
Change at STC/EW; Fatigue Number Analyzed 161 participants 64 participants
-3.11  (28.64) -4.69  (21.30)
Change at EoCTR; Fatigue Number Analyzed 142 participants 63 participants
-6.69  (26.78) -3.97  (24.27)
Change at FUV1; Fatigue Number Analyzed 123 participants 63 participants
-6.37  (26.61) -4.23  (22.99)
Change at FUV2; Fatigue Number Analyzed 113 participants 63 participants
-6.64  (24.55) -1.85  (24.70)
Change at FUV3; Fatigue Number Analyzed 95 participants 62 participants
-5.79  (23.29) -2.42  (23.73)
Change at FUV4; Fatigue Number Analyzed 76 participants 47 participants
-9.65  (26.84) -0.35  (25.18)
Change at FUV5; Fatigue Number Analyzed 56 participants 19 participants
-6.55  (25.56) 3.51  (23.95)
Change at FUV6; Fatigue Number Analyzed 33 participants 5 participants
-5.05  (24.82) 3.33  (24.72)
Change at FUV7; Fatigue Number Analyzed 13 participants 1 participants
-10.26  (30.08) -33.33
Change at FUV8; Fatigue Number Analyzed 5 participants 1 participants
-6.67  (19.00) 0.00
Change at FUV9; Fatigue Number Analyzed 2 participants 0 participants
-8.33  (11.79)
Baseline; Infection Number Analyzed 175 participants 69 participants
15.92  (17.63) 14.01  (18.99)
Change at C1D1; Infection Number Analyzed 175 participants 67 participants
0.0  (0.0) -2.24  (20.03)
Change at C2D1; Infection Number Analyzed 170 participants 67 participants
-0.02  (19.98) -3.61  (21.72)
Change at C3D1; Infection Number Analyzed 159 participants 63 participants
-1.66  (19.21) -1.32  (20.48)
Change at C4D1; Infection Number Analyzed 152 participants 64 participants
-1.44  (22.07) -3.13  (21.28)
Change at C5D1; Infection Number Analyzed 147 participants 65 participants
-1.91  (24.00) -2.56  (23.47)
Change at C6D1; Infection Number Analyzed 143 participants 65 participants
-1.09  (20.66) -2.95  (20.54)
Change at STC/EW; Infection Number Analyzed 161 participants 64 participants
-0.12  (23.28) -1.69  (23.34)
Change at EoCTR; Infection Number Analyzed 142 participants 63 participants
-0.55  (21.73) -3.44  (25.78)
Change at FUV1; Infection Number Analyzed 121 participants 63 participants
1.08  (18.77) -2.65  (26.51)
Change at FUV2; Infection Number Analyzed 113 participants 63 participants
0.05  (23.29) -0.53  (25.74)
Change at FUV3; Infection Number Analyzed 95 participants 62 participants
-1.90  (16.97) -0.54  (26.48)
Change at FUV4; Infection Number Analyzed 76 participants 47 participants
-4.24  (16.71) 0.53  (25.56)
Change at FUV5; Infection Number Analyzed 56 participants 19 participants
-4.51  (22.66) 7.46  (27.20)
Change at FUV6; Infection Number Analyzed 33 participants 5 participants
-1.60  (18.90) 8.33  (15.59)
Change at FUV7; Infection Number Analyzed 13 participants 1 participants
-0.43  (21.84) -16.67
Change at FUV8; Infection Number Analyzed 5 participants 1 participants
8.89  (23.36) -25.00
Change at FUV9; Infection Number Analyzed 2 participants 0 participants
-2.78  (3.93)
27.Post-Hoc Outcome
Title Euro QoL 5 Dimension (EQ-5D) Questionnaire Score
Hide Description [Not Specified]
Time Frame Baseline, D1 of Cycles 1, 2, 3, 4, 5, 6, STC/EW visit (up to C6D28), EoCTR visit (8 to 12 weeks after C6D1), and FUVs (every 12 weeks after EoCTR up to 3 years); Cycle length = 28 days
Outcome Measure Data Not Reported
Time Frame Baseline up to Follow-up (maximum up to Data Cut-off date, overall approximately 3 years)
Adverse Event Reporting Description Analysis was performed on safety evaluable (SE) population, which included all randomized participants who received at least one dose of study treatment (venetoclax, rituximab, or bendamustine), with participants grouped according to the actual treatment received.
 
Arm/Group Title Bendamustine + Rituximab Venetoclax + Rituximab
Hide Arm/Group Description Participants received bendamustine at a dose of 70 mg/m^2 via IV infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6. Participants were initially placed on a venetoclax ramp-up period of 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
All-Cause Mortality
Bendamustine + Rituximab Venetoclax + Rituximab
Affected / at Risk (%) Affected / at Risk (%)
Total   27/188 (14.36%)   15/194 (7.73%) 
Show Serious Adverse Events Hide Serious Adverse Events
Bendamustine + Rituximab Venetoclax + Rituximab
Affected / at Risk (%) Affected / at Risk (%)
Total   81/188 (43.09%)   90/194 (46.39%) 
Blood and lymphatic system disorders     
Anaemia * 1  5/188 (2.66%)  3/194 (1.55%) 
Autoimmune haemolytic anaemia * 1  3/188 (1.60%)  3/194 (1.55%) 
Disseminated intravascular coagulation * 1  0/188 (0.00%)  1/194 (0.52%) 
Febrile neutropenia * 1  16/188 (8.51%)  7/194 (3.61%) 
Immune thrombocytopenic purpura * 1  0/188 (0.00%)  1/194 (0.52%) 
Leukocytosis * 1  1/188 (0.53%)  0/194 (0.00%) 
Neutropenia * 1  3/188 (1.60%)  3/194 (1.55%) 
Pancytopenia * 1  0/188 (0.00%)  1/194 (0.52%) 
Thrombocytopenia * 1  2/188 (1.06%)  2/194 (1.03%) 
Cardiac disorders     
Acute myocardial infarction * 1  1/188 (0.53%)  0/194 (0.00%) 
Angina pectoris * 1  0/188 (0.00%)  1/194 (0.52%) 
Atrial fibrillation * 1  1/188 (0.53%)  0/194 (0.00%) 
Cardiac failure * 1  0/188 (0.00%)  1/194 (0.52%) 
Coronary artery disease * 1  1/188 (0.53%)  0/194 (0.00%) 
Myocardial infarction * 1  0/188 (0.00%)  2/194 (1.03%) 
Ventricular tachycardia * 1  0/188 (0.00%)  1/194 (0.52%) 
Ear and labyrinth disorders     
Deafness * 1  0/188 (0.00%)  1/194 (0.52%) 
Vertigo * 1  0/188 (0.00%)  1/194 (0.52%) 
Eye disorders     
Eye haemorrhage * 1  0/188 (0.00%)  1/194 (0.52%) 
Gastrointestinal disorders     
Abdominal pain * 1  0/188 (0.00%)  1/194 (0.52%) 
Anal fistula * 1  1/188 (0.53%)  0/194 (0.00%) 
Ascites * 1  0/188 (0.00%)  1/194 (0.52%) 
Colitis * 1  1/188 (0.53%)  0/194 (0.00%) 
Crohn's disease * 1  0/188 (0.00%)  1/194 (0.52%) 
Diarrhoea * 1  0/188 (0.00%)  2/194 (1.03%) 
Dyspepsia * 1  0/188 (0.00%)  1/194 (0.52%) 
Gastrointestinal haemorrhage * 1  0/188 (0.00%)  1/194 (0.52%) 
Nausea * 1  1/188 (0.53%)  0/194 (0.00%) 
Oesophageal obstruction * 1  0/188 (0.00%)  1/194 (0.52%) 
Small intestinal obstruction * 1  0/188 (0.00%)  1/194 (0.52%) 
Vomiting * 1  1/188 (0.53%)  1/194 (0.52%) 
General disorders     
Asthenia * 1  1/188 (0.53%)  0/194 (0.00%) 
Hyperpyrexia * 1  1/188 (0.53%)  1/194 (0.52%) 
Malaise * 1  1/188 (0.53%)  0/194 (0.00%) 
Pyrexia * 1  13/188 (6.91%)  5/194 (2.58%) 
Sudden cardiac death * 1  0/188 (0.00%)  1/194 (0.52%) 
Sudden death * 1  1/188 (0.53%)  0/194 (0.00%) 
Unevaluable event * 1  1/188 (0.53%)  0/194 (0.00%) 
Hepatobiliary disorders     
Bile duct obstruction * 1  0/188 (0.00%)  1/194 (0.52%) 
Infections and infestations     
Abscess neck * 1  1/188 (0.53%)  0/194 (0.00%) 
Appendicitis * 1  0/188 (0.00%)  2/194 (1.03%) 
Atypical pneumonia * 1  1/188 (0.53%)  0/194 (0.00%) 
Bronchitis * 1  2/188 (1.06%)  0/194 (0.00%) 
Bronchopulmonary aspergillosis * 1  1/188 (0.53%)  0/194 (0.00%) 
Campylobacter gastroenteritis * 1  0/188 (0.00%)  1/194 (0.52%) 
Cellulitis * 1  1/188 (0.53%)  0/194 (0.00%) 
Clostridium difficile colitis * 1  1/188 (0.53%)  0/194 (0.00%) 
Cystitis * 1  0/188 (0.00%)  1/194 (0.52%) 
Diverticulitis * 1  0/188 (0.00%)  1/194 (0.52%) 
Erysipelas * 1  0/188 (0.00%)  1/194 (0.52%) 
Escherichia sepsis * 1  1/188 (0.53%)  0/194 (0.00%) 
Gastroenteritis rotavirus * 1  0/188 (0.00%)  1/194 (0.52%) 
Gastroenteritis viral * 1  1/188 (0.53%)  0/194 (0.00%) 
Haemophilus infection * 1  0/188 (0.00%)  1/194 (0.52%) 
Hepatitis B * 1  1/188 (0.53%)  0/194 (0.00%) 
Herpes simplex otitis externa * 1  0/188 (0.00%)  1/194 (0.52%) 
Herpes zoster * 1  0/188 (0.00%)  1/194 (0.52%) 
Influenza * 1  2/188 (1.06%)  3/194 (1.55%) 
Listeria sepsis * 1  1/188 (0.53%)  0/194 (0.00%) 
Localised infection * 1  1/188 (0.53%)  0/194 (0.00%) 
Lung infection * 1  0/188 (0.00%)  3/194 (1.55%) 
Meningitis * 1  0/188 (0.00%)  1/194 (0.52%) 
Moraxella infection * 1  0/188 (0.00%)  1/194 (0.52%) 
Neutropenic sepsis * 1  1/188 (0.53%)  0/194 (0.00%) 
Peritoneal tuberculosis * 1  0/188 (0.00%)  1/194 (0.52%) 
Pharyngitis * 1  2/188 (1.06%)  0/194 (0.00%) 
Pneumococcal bacteraemia * 1  1/188 (0.53%)  0/194 (0.00%) 
Pneumocystis jirovecii pneumonia * 1  1/188 (0.53%)  0/194 (0.00%) 
Pneumonia * 1  15/188 (7.98%)  16/194 (8.25%) 
Pneumonia influenzal * 1  0/188 (0.00%)  1/194 (0.52%) 
Pneumonia legionella * 1  1/188 (0.53%)  0/194 (0.00%) 
Pneumonia streptococcal * 1  0/188 (0.00%)  1/194 (0.52%) 
Respiratory tract infection * 1  0/188 (0.00%)  2/194 (1.03%) 
Respiratory tract infection fungal * 1  0/188 (0.00%)  1/194 (0.52%) 
Respiratory tract infection viral * 1  0/188 (0.00%)  1/194 (0.52%) 
Rhinovirus infection * 1  0/188 (0.00%)  1/194 (0.52%) 
Scedosporium infection * 1  1/188 (0.53%)  0/194 (0.00%) 
Sepsis * 1  4/188 (2.13%)  1/194 (0.52%) 
Septic shock * 1  1/188 (0.53%)  0/194 (0.00%) 
Sinusitis * 1  1/188 (0.53%)  2/194 (1.03%) 
Staphylococcal infection * 1  1/188 (0.53%)  0/194 (0.00%) 
Tooth abscess * 1  0/188 (0.00%)  1/194 (0.52%) 
Upper respiratory tract infection * 1  2/188 (1.06%)  3/194 (1.55%) 
Urinary tract infection * 1  1/188 (0.53%)  1/194 (0.52%) 
Urinary tract infection pseudomonal * 1  0/188 (0.00%)  1/194 (0.52%) 
Urosepsis * 1  1/188 (0.53%)  0/194 (0.00%) 
Varicella zoster virus infection * 1  1/188 (0.53%)  0/194 (0.00%) 
Viral infection * 1  0/188 (0.00%)  1/194 (0.52%) 
Viral upper respiratory tract infection * 1  0/188 (0.00%)  1/194 (0.52%) 
Lower respiratory tract infection * 1  1/188 (0.53%)  0/194 (0.00%) 
Parainfluenzae virus infection * 1  1/188 (0.53%)  0/194 (0.00%) 
Injury, poisoning and procedural complications     
Humerus fracture * 1  0/188 (0.00%)  1/194 (0.52%) 
Infusion related reaction * 1  6/188 (3.19%)  1/194 (0.52%) 
Tendon rupture * 1  1/188 (0.53%)  0/194 (0.00%) 
Investigations     
Body temperature increased * 1  1/188 (0.53%)  0/194 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  0/188 (0.00%)  1/194 (0.52%) 
Dehydration * 1  0/188 (0.00%)  2/194 (1.03%) 
Diabetes mellitus * 1  0/188 (0.00%)  1/194 (0.52%) 
Fluid overload * 1  0/188 (0.00%)  1/194 (0.52%) 
Hyperkalaemia * 1  0/188 (0.00%)  2/194 (1.03%) 
Hyperphosphataemia * 1  0/188 (0.00%)  2/194 (1.03%) 
Tumour lysis syndrome * 1  1/188 (0.53%)  4/194 (2.06%) 
Musculoskeletal and connective tissue disorders     
Intervertebral disc protrusion * 1  1/188 (0.53%)  0/194 (0.00%) 
Musculoskeletal chest pain * 1  1/188 (0.53%)  0/194 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute myeloid leukaemia * 1  1/188 (0.53%)  0/194 (0.00%) 
Adenocarcinoma gastric * 1  0/188 (0.00%)  1/194 (0.52%) 
Adenocarcinoma of colon * 1  1/188 (0.53%)  0/194 (0.00%) 
Basal cell carcinoma * 1  0/188 (0.00%)  1/194 (0.52%) 
Colon cancer * 1  0/188 (0.00%)  1/194 (0.52%) 
Colorectal cancer * 1  0/188 (0.00%)  2/194 (1.03%) 
Lung neoplasm malignant * 1  2/188 (1.06%)  0/194 (0.00%) 
Lymphoma * 1  1/188 (0.53%)  0/194 (0.00%) 
Malignant melanoma * 1  0/188 (0.00%)  1/194 (0.52%) 
Medullary thyroid cancer * 1  1/188 (0.53%)  0/194 (0.00%) 
Metastatic malignant melanoma * 1  0/188 (0.00%)  1/194 (0.52%) 
Myelodysplastic syndrome * 1  0/188 (0.00%)  2/194 (1.03%) 
Pancreatic carcinoma * 1  0/188 (0.00%)  1/194 (0.52%) 
Prostate cancer * 1  1/188 (0.53%)  0/194 (0.00%) 
Prostatic adenoma * 1  0/188 (0.00%)  1/194 (0.52%) 
Skin cancer * 1  0/188 (0.00%)  1/194 (0.52%) 
Squamous cell carcinoma * 1  1/188 (0.53%)  3/194 (1.55%) 
Transitional cell carcinoma * 1  1/188 (0.53%)  0/194 (0.00%) 
Nervous system disorders     
Dizziness * 1  0/188 (0.00%)  1/194 (0.52%) 
Haemorrhagic stroke * 1  1/188 (0.53%)  0/194 (0.00%) 
Lacunar infarction * 1  0/188 (0.00%)  1/194 (0.52%) 
Polyneuropathy * 1  1/188 (0.53%)  0/194 (0.00%) 
Status epilepticus * 1  0/188 (0.00%)  1/194 (0.52%) 
Syncope * 1  1/188 (0.53%)  0/194 (0.00%) 
Renal and urinary disorders     
Acute kidney injury * 1  1/188 (0.53%)  1/194 (0.52%) 
Nephrolithiasis * 1  0/188 (0.00%)  1/194 (0.52%) 
Renal impairment * 1  1/188 (0.53%)  0/194 (0.00%) 
Reproductive system and breast disorders     
Cervical dysplasia * 1  0/188 (0.00%)  1/194 (0.52%) 
Uterine haemorrhage * 1  0/188 (0.00%)  1/194 (0.52%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure * 1  0/188 (0.00%)  1/194 (0.52%) 
Bronchiectasis * 1  0/188 (0.00%)  1/194 (0.52%) 
Lung disorder * 1  0/188 (0.00%)  1/194 (0.52%) 
Pulmonary embolism * 1  1/188 (0.53%)  1/194 (0.52%) 
Skin and subcutaneous tissue disorders     
Dermatitis allergic * 1  1/188 (0.53%)  0/194 (0.00%) 
Vascular disorders     
Aortic stenosis * 1  1/188 (0.53%)  0/194 (0.00%) 
Deep vein thrombosis * 1  1/188 (0.53%)  1/194 (0.52%) 
Embolism * 1  1/188 (0.53%)  0/194 (0.00%) 
Hypotension * 1  5/188 (2.66%)  0/194 (0.00%) 
1
Term from vocabulary, MedDRA v19.1
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Bendamustine + Rituximab Venetoclax + Rituximab
Affected / at Risk (%) Affected / at Risk (%)
Total   176/188 (93.62%)   190/194 (97.94%) 
Blood and lymphatic system disorders     
Anaemia * 1  40/188 (21.28%)  28/194 (14.43%) 
Neutropenia * 1  82/188 (43.62%)  118/194 (60.82%) 
Thrombocytopenia * 1  42/188 (22.34%)  24/194 (12.37%) 
Gastrointestinal disorders     
Abdominal pain * 1  6/188 (3.19%)  13/194 (6.70%) 
Constipation * 1  39/188 (20.74%)  27/194 (13.92%) 
Diarrhoea * 1  31/188 (16.49%)  76/194 (39.18%) 
Nausea * 1  64/188 (34.04%)  41/194 (21.13%) 
Vomiting * 1  22/188 (11.70%)  15/194 (7.73%) 
General disorders     
Chills * 1  16/188 (8.51%)  8/194 (4.12%) 
Fatigue * 1  39/188 (20.74%)  34/194 (17.53%) 
Oedema peripheral * 1  7/188 (3.72%)  11/194 (5.67%) 
Pyrexia * 1  33/188 (17.55%)  27/194 (13.92%) 
Infections and infestations     
Bronchitis * 1  13/188 (6.91%)  20/194 (10.31%) 
Conjunctivitis * 1  5/188 (2.66%)  10/194 (5.15%) 
Lower respiratory tract infection * 1  4/188 (2.13%)  11/194 (5.67%) 
Nasopharyngitis * 1  10/188 (5.32%)  22/194 (11.34%) 
Oral herpes * 1  12/188 (6.38%)  8/194 (4.12%) 
Pharyngitis * 1  1/188 (0.53%)  13/194 (6.70%) 
Pneumonia * 1  11/188 (5.85%)  5/194 (2.58%) 
Sinusitis * 1  5/188 (2.66%)  17/194 (8.76%) 
Upper respiratory tract infection * 1  28/188 (14.89%)  41/194 (21.13%) 
Urinary tract infection * 1  7/188 (3.72%)  11/194 (5.67%) 
Injury, poisoning and procedural complications     
Infusion related reaction * 1  40/188 (21.28%)  15/194 (7.73%) 
Investigations     
Alanine aminotransferase increased * 1  10/188 (5.32%)  9/194 (4.64%) 
Neutrophil count decreased * 1  13/188 (6.91%)  11/194 (5.67%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  17/188 (9.04%)  8/194 (4.12%) 
Hyperkalaemia * 1  0/188 (0.00%)  11/194 (5.67%) 
Hypokalaemia * 1  7/188 (3.72%)  12/194 (6.19%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  10/188 (5.32%)  12/194 (6.19%) 
Back pain * 1  11/188 (5.85%)  15/194 (7.73%) 
Muscle spasms * 1  11/188 (5.85%)  4/194 (2.06%) 
Nervous system disorders     
Dizziness * 1  10/188 (5.32%)  12/194 (6.19%) 
Headache * 1  19/188 (10.11%)  21/194 (10.82%) 
Psychiatric disorders     
Insomnia * 1  12/188 (6.38%)  21/194 (10.82%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  31/188 (16.49%)  35/194 (18.04%) 
Dyspnoea * 1  14/188 (7.45%)  11/194 (5.67%) 
Oropharyngeal pain * 1  7/188 (3.72%)  10/194 (5.15%) 
Productive cough * 1  4/188 (2.13%)  12/194 (6.19%) 
Skin and subcutaneous tissue disorders     
Pruritus * 1  8/188 (4.26%)  10/194 (5.15%) 
Rash * 1  24/188 (12.77%)  14/194 (7.22%) 
Vascular disorders     
Hypertension * 1  7/188 (3.72%)  12/194 (6.19%) 
1
Term from vocabulary, MedDRA v19.1
*
Indicates events were collected by non-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.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800-821-8590
EMail: genentech@druginfo.com
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02005471     History of Changes
Other Study ID Numbers: GO28667
2013-002110-12 ( EudraCT Number )
First Submitted: December 4, 2013
First Posted: December 9, 2013
Results First Submitted: May 3, 2018
Results First Posted: October 1, 2018
Last Update Posted: September 9, 2019