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)

• ClinicalTrials.gov Identifier: NCT02005471
• Recruitment Status: Completed
• First Posted: December 9, 2013
• Results First Posted: October 1, 2018
• Last Update Posted: October 17, 2023
• Sponsor: Hoffmann-La Roche
• 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

Participant Flow

Recruitment Details

A total 389 participants took part in the study across 109 investigative sites in 20 countries i.e., Korea, Taiwan, Australia, New Zealand, Czech Republic, Hungary, Poland, Russia, Canada, United States of America, Austria, Belgium, Germany, Denmark, Spain, France, United Kingdom, Italy, Netherlands and Sweden from 17 March 2014 to 03 August 2022. The trial consisted of a main study and an optional Retreatment/Crossover (R/C) sub study.

Pre-assignment Details

Of the 389 participants enrolled 7 participants in the bendamustine + rituximab (BR) arm did not receive a valid dose of study treatment.

Arm/Group Title	Bendamustine + Rituximab Main Study	Venetoclax + Rituximab Main Study	Bendamustine + Rituximab Crossover Substudy	Venetoclax + Rituximab Re-Treatment Substudy
Arm/Group Description	Participants received bendamustine at a dose of 70 milligrams per meter square (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 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, orally, QD. Participants continued receiving venetoclax at a dose of 400 mg, orally, QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to progressive disease (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.	Participants who entered the crossover substudy had a 5-week venetoclax dose ramp-up period to reach the target dose of 400 mg QD. Following the venetoclax ramp-up period, participants received 6 cycles of rituximab, 375 mg/m^2, as IV infusion on the Day 1 of each 28-day cycle. Participants who did not progress following the completion of the 6 cycles continued to receive venetoclax monotherapy until disease progression or for a maximum of 2 years from Cycle 1 crossover Day 1 of the substudy.	Participants who entered the re-treatment substudy had a 5-week venetoclax dose ramp-up period to reach the target dose of 400 mg QD. Following the venetoclax ramp-up period, participants received 6 cycles of rituximab consisting of a single infusion on the first day of each 28-day cycle. Participants who did not progress following the completion of the 6 cycles continued to receive venetoclax monotherapy until disease progression or for a maximum of 2 year from Cycle 1 re-treatment Day 1 of the substudy.
Period Title: Main Study
Started	195	194	0	0
Safety Evaluable (SE) Population [1]	188	194	0	0
Completed	71	118	0	0
Not Completed	124	76	0	0
Reason Not Completed
Adverse Event	0	1	0	0
Death	83	52	0	0
Lost to Follow-up	4	5	0	0
Physician Decision	3	1	0	0
Withdrawal by Subject	26	11	0	0
Reason not Specified	0	6	0	0
Randomized but not Dosed	8	0	0	0
[1] SE population included all randomized participants who received at least one dose of study treatment with participants grouped according to the actual treatment received.
Period Title: Re-Treatment/Crossover (R/C) Substudy
Started	0 [1]	0 [1]	9 [2]	25 [3]
Completed	0	0	7	15
Not Completed	0	0	2	10
Reason Not Completed
Withdrawal by Subject	0	0	0	1
Lost to Follow-up	0	0	1	1
Death	0	0	1	8
[1] Following the end of main study, participants who had progressed clinically and were in need of therapy participated in the Re-Treatment/Crossover Substudy at the discretion of the investigator.; [2] 9 participants from BR arm entered R/C substudy.; [3] 25 participants from VR arm entered R/C substudy.

Baseline Characteristics

Arm/Group Title		Bendamustine + Rituximab Main Study	Venetoclax + Rituximab Main Study	Total
Arm/Group Description		Participants received bendamustine at a dose of 70 milligrams per meter square (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 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, orally, QD. Participants continued receiving venetoclax at a dose of 400 mg, 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
Baseline Analysis Population Description		Intent-to-treat (ITT) population 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%

Outcome Measures

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
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. Percentages are rounded off.
Time Frame	Baseline up to PD or death from any cause, whichever occurred first (up to approximately 8 years 5 months)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, with participants grouped according to randomized treatment group, regardless of the actual treatment received.

Arm/Group Title	Bendamustine + Rituximab Main Study	Venetoclax + Rituximab Main Study
Arm/Group Description:	Participants received bendamustine at a dose of 70 milligrams per meter square (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 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, orally, QD. Participants continued receiving venetoclax at a dose of 400 mg, 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
	88.7	70.1

2. Primary Outcome

Title	Progression-Free Survival (PFS) as Assessed by the Investigator Using Standard iwCLL Guidelines
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 8 years 5 months)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, with participants grouped according to randomized treatment group, regardless of the actual treatment received.

Arm/Group Title	Bendamustine + Rituximab Main Study	Venetoclax + Rituximab Main Study
Arm/Group Description:	Participants received bendamustine at a dose of 70 milligrams per meter square (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 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, orally, QD. Participants continued receiving venetoclax at a dose of 400 mg, 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 21.7)	54.7; (52.3 to 59.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab Main Study, Venetoclax + Rituximab Main Study
	Comments	Stratified analysis: 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	0.23
	Confidence Interval	(2-Sided) 95%; 0.18 to 0.29
	Estimation Comments	Hazard ratio was estimated by Cox regression model.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab Main Study, Venetoclax + Rituximab Main Study
	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	0.25
	Confidence Interval	(2-Sided) 95%; 0.19 to 0.31
	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
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. No new IRC data was generated post the primary analysis.
Time Frame	Baseline up to PD or death, whichever occurred first (up to approximately 3 years)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, with participants grouped according to randomized treatment group, regardless of the actual treatment received.

Arm/Group Title	Bendamustine + Rituximab Main Study	Venetoclax + Rituximab Main Study
Arm/Group Description:	Participants received bendamustine at a dose of 70 milligrams per meter square (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 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, orally, QD. Participants continued receiving venetoclax at a dose of 400 mg, 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
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. No new IRC data was generated post the primary analysis.
Time Frame	Baseline up to PD or death, whichever occurred first (up to approximately 3 years)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, with participants grouped according to randomized treatment group, regardless of the actual treatment received.

Arm/Group Title	Bendamustine + Rituximab Main Study	Venetoclax + Rituximab Main Study
Arm/Group Description:	Participants received bendamustine at a dose of 70 milligrams per meter square (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 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, orally, QD. Participants continued receiving venetoclax at a dose of 400 mg, 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.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab Main Study, Venetoclax + Rituximab Main Study
	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab Main Study, Venetoclax + Rituximab Main Study
	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
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. Percentages are rounded off.
Time Frame	Baseline up to PD or death, whichever occurred first (up to approximately 8 years 5 months)

Outcome Measure Data

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
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
	80.4	80.4

6. Secondary Outcome

Title	PFS as Assessed by the Investigator Using Standard iwCLL Guidelines in Participants With 17p Deletion as Identified by FISH Test
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 8 years 5 months)

Outcome Measure Data

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
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)	47.9; (37.4 to 59.9)

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	0.35
	Confidence Interval	(2-Sided) 95%; 0.21 to 0.57
	Estimation Comments	Hazard ratio was estimated by Cox regression model.

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	0.35
	Confidence Interval	(2-Sided) 95%; 0.22 to 0.56
	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
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. No new IRC data was generated post the primary analysis.
Time Frame	Baseline up to PD or death, whichever occurred first (up to approximately 3 years)

Outcome Measure Data

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
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
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. No new IRC data was generated post the primary analysis.
Time Frame	Baseline up to PD or death, whichever occurred first (up to approximately 3 years)

Outcome Measure Data

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
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.

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.

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
Description	Response was assessed by investigator according to 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 following: peripheral blood lymphocytes, lymphadenopathy, spleen and/or liver enlargement; and 1 of 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. 95% CI was computed using Pearson-Clopper method.Percentages are rounded off.
Time Frame	Baseline up to approximately 8 years 5 months

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, with participants grouped according to randomized treatment group, regardless of the actual treatment received.

Arm/Group Title	Bendamustine + Rituximab Main Study	Venetoclax + Rituximab Main Study
Arm/Group Description:	Participants received bendamustine at a dose of 70 milligrams per meter square (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 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, orally, QD. Participants continued receiving venetoclax at a dose of 400 mg, 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
CR	8.2; (4.76 to 12.98)	26.3; (20.24 to 33.07)
CRi	0.5; (0.01 to 2.82)	1.5; (0.32 to 4.45)
nPR	6.2; (3.22 to 10.50)	3.6; (1.46 to 7.29)
PR	52.8; (45.56 to 59.99)	61.9; (54.62 to 68.72)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab Main Study, Venetoclax + Rituximab Main Study
	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	95% CI for rates were constructed using Pearson- Clopper method. 95% CI for difference in rates were constructed using Anderson-Hauck method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab Main Study, Venetoclax + Rituximab Main Study
	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
Description	Response was assessed by IRC according to 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, 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 2 of following: peripheral blood lymphocytes, lymphadenopathy, spleen and/or liver enlargement; 1 of 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. 95% CI was computed using Pearson-Clopper method.No new IRC data was generated post primary analysis.
Time Frame	Baseline up to last FUV (up to approximately 3 years)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, with participants grouped according to randomized treatment group, regardless of the actual treatment received.

Arm/Group Title	Bendamustine + Rituximab Main Study	Venetoclax + Rituximab Main Study
Arm/Group Description:	Participants received bendamustine at a dose of 70 milligrams per meter square (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 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, orally, QD. Participants continued receiving venetoclax at a dose of 400 mg, 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)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab Main Study, Venetoclax + Rituximab Main Study
	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	95% CI for rates were constructed using Pearson- Clopper method. 95% CI for difference in rates were constructed using Anderson-Hauck method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab Main Study, Venetoclax + Rituximab Main Study
	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.

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
Description	Response was assessed by investigator according to 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 2 of following: peripheral blood lymphocytes, lymphadenopathy, spleen and/or liver enlargement; and 1 of 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. 95% CI was computed using Pearson-Clopper method. Percentages are rounded off.
Time Frame	End of combination treatment response (EoCTR) visit (8 to 12 weeks after Cycle [C] 6 Day [1]); Cycle length = 28 days

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, with participants grouped according to randomized treatment group, regardless of the actual treatment received.

Arm/Group Title	Bendamustine + Rituximab Main Study	Venetoclax + Rituximab Main Study
Arm/Group Description:	Participants received bendamustine at a dose of 70 milligrams per meter square (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 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, orally, QD. Participants continued receiving venetoclax at a dose of 400 mg, 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
	63.1; (55.89 to 69.86)	88.1; (82.74 to 92.33)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab Main Study, Venetoclax + Rituximab Main Study
	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	25.07
	Confidence Interval	(2-Sided) 95%; 16.63 to 33.51
	Estimation Comments	The 95% CI was computed using Anderson-Hauck method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab Main Study, Venetoclax + Rituximab Main Study
	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 7.88
	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
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

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, with participants grouped according to randomized treatment group, regardless of the actual treatment received.

Arm/Group Title	Bendamustine + Rituximab Main Study	Venetoclax + Rituximab Main Study
Arm/Group Description:	Participants received bendamustine at a dose of 70 milligrams per meter square (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 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, orally, QD. Participants continued receiving venetoclax at a dose of 400 mg, 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)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab Main Study, Venetoclax + Rituximab Main Study
	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab Main Study, Venetoclax + Rituximab Main Study
	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
Description	Percentage of participants who died from any cause, during the study, was reported. Percentage is rounded off.
Time Frame	Baseline up to approximately 8 years 5 months

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, with participants grouped according to randomized treatment group, regardless of the actual treatment received.

Arm/Group Title	Bendamustine + Rituximab Main Study	Venetoclax + Rituximab Main Study
Arm/Group Description:	Participants received bendamustine at a dose of 70 milligrams per meter square (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 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, orally, QD. Participants continued receiving venetoclax at a dose of 400 mg, 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
	43.1	30.9

14. Secondary Outcome

Title	Overall Survival (OS)
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 approximately 8 years 5 months

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, with participants grouped according to randomized treatment group, regardless of the actual treatment received.

Arm/Group Title	Bendamustine + Rituximab Main Study	Venetoclax + Rituximab Main Study
Arm/Group Description:	Participants received bendamustine at a dose of 70 milligrams per meter square (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 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, orally, QD. Participants continued receiving venetoclax at a dose of 400 mg, 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
	87.8 [1]; (70.1 to NA)	NA [2]; (NA to NA)

[1]

Upper limit was not estimable due to low number of participants with event.

[2]

Median, lower limit and upper limit were not estimable due to low number of participants with event.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab Main Study, Venetoclax + Rituximab Main Study
	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	0.0002
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.53
	Confidence Interval	(2-Sided) 95%; 0.37 to 0.74
	Estimation Comments	Hazard ratio was estimated by Cox regression model.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab Main Study, Venetoclax + Rituximab Main Study
	Comments	Unstratified Analysis
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0003
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.54
	Confidence Interval	(2-Sided) 95%; 0.39 to 0.76
	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
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. Percentages are rounded off.
Time Frame	Baseline up to PD/relapse, start of a new anti-CLL therapy, or death from any cause, whichever occurred first (approximately 8 years 5 months)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, with participants grouped according to randomized treatment group, regardless of the actual treatment received.

Arm/Group Title	Bendamustine + Rituximab Main Study	Venetoclax + Rituximab Main Study
Arm/Group Description:	Participants received bendamustine at a dose of 70 milligrams per meter square (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 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, orally, QD. Participants continued receiving venetoclax at a dose of 400 mg, 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
	89.2	71.1

16. Secondary Outcome

Title	Event-Free Survival (EFS) as Assessed by the Investigator Using iwCLL Guidelines
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 (approximately 8 years 5 months)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, with participants grouped according to randomized treatment group, regardless of the actual treatment received.

Arm/Group Title	Bendamustine + Rituximab Main Study	Venetoclax + Rituximab Main Study
Arm/Group Description:	Participants received bendamustine at a dose of 70 milligrams per meter square (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 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, orally, QD. Participants continued receiving venetoclax at a dose of 400 mg, 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; (14.2 to 21.0)	53.7; (48.5 to 59.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab Main Study, Venetoclax + Rituximab Main Study
	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	0.22
	Confidence Interval	(2-Sided) 95%; 0.17 to 0.29
	Estimation Comments	Hazard ratio was estimated by Cox regression model.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab Main Study, Venetoclax + Rituximab Main Study
	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	0.25
	Confidence Interval	(2-Sided) 95%; 0.19 to 0.31
	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
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. Percentage is rounded off.
Time Frame	From time of achieving best overall response until PD or death from any cause, whichever occurred first (up to approximately 8 years 5 months)

Outcome Measure Data

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 Main Study	Venetoclax + Rituximab Main Study
Arm/Group Description:	Participants received bendamustine at a dose of 70 milligrams per meter square (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 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, orally, QD. Participants continued receiving venetoclax at a dose of 400 mg, 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
	95.5	68.5

18. Secondary Outcome

Title	Duration of Responses (DOR) as Assessed by the Investigator Using iwCLL Guidelines
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 8 years 5 months)

Outcome Measure Data

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 Main Study	Venetoclax + Rituximab Main Study
Arm/Group Description:	Participants received bendamustine at a dose of 70 milligrams per meter square (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 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, orally, QD. Participants continued receiving venetoclax at a dose of 400 mg, 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
	19.1; (16.1 to 23.6)	53.6; (49.1 to 57.0)

19. Secondary Outcome

Title	Percentage of Participants With Start of New Anti-CLL Treatment or Death as Assessed by the Investigator
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. Percentage is rounded off.
Time Frame	Baseline up to start of new ani-CLL therapy or death, whichever occurred first (up to approximately 8 years 5 months)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, with participants grouped according to randomized treatment group, regardless of the actual treatment received.

Arm/Group Title	Bendamustine + Rituximab Main Study	Venetoclax + Rituximab Main Study
Arm/Group Description:	Participants received bendamustine at a dose of 70 milligrams per meter square (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 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, orally, QD. Participants continued receiving venetoclax at a dose of 400 mg, 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
	81.5	62.4

20. Secondary Outcome

Title	Time to New Anti-CLL Treatment (TTNT) as Assessed by the Investigator
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 8 years 5 months)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, with participants grouped according to randomized treatment group, regardless of the actual treatment received.

Arm/Group Title	Bendamustine + Rituximab Main Study	Venetoclax + Rituximab Main Study
Arm/Group Description:	Participants received bendamustine at a dose of 70 milligrams per meter square (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 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, orally, QD. Participants continued receiving venetoclax at a dose of 400 mg, 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
	24.0; (20.7 to 29.5)	63.0; (56.1 to 73.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab Main Study, Venetoclax + Rituximab Main Study
	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	0.30
	Confidence Interval	(2-Sided) 95%; 0.23 to 0.39
	Estimation Comments	Hazard ratio was estimated by Cox regression model.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab Main Study, Venetoclax + Rituximab Main Study
	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	0.32
	Confidence Interval	(2-Sided) 95%; 0.25 to 0.41
	Estimation Comments	Hazard ratio was estimated by Cox regression model.

21. Secondary Outcome

Title	Percentage of Participants With Minimal Residual Disease (MRD) Negativity in Peripheral Blood
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 was reported. The 95% CI was computed using Pearson-Clopper method. Percentage is rounded off.
Time Frame	EoCTR visit (8 to 12 weeks after C6D1); Cycle length = 28 days

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, with participants grouped according to randomized treatment group, regardless of the actual treatment received.

Arm/Group Title	Bendamustine + Rituximab Main Study	Venetoclax + Rituximab Main Study
Arm/Group Description:	Participants received bendamustine at a dose of 70 milligrams per meter square (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 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, orally, QD. Participants continued receiving venetoclax at a dose of 400 mg, 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)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab Main Study, Venetoclax + Rituximab Main Study
	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab Main Study, Venetoclax + Rituximab Main Study
	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	Percentage of Participants With MRD Negativity in Bone Marrow
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 flow cytometry technique. Percentage of participants with MRD-negativity was reported. The 95% CI was computed using Pearson-Clopper method. Percentages are rounded off.
Time Frame	EoCTR visit (8 to 12 weeks after C6D1); Cycle length = 28 days

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, with participants grouped according to randomized treatment group, regardless of the actual treatment received.

Arm/Group Title	Bendamustine + Rituximab Main Study	Venetoclax + Rituximab Main Study
Arm/Group Description:	Participants received bendamustine at a dose of 70 milligrams per meter square (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 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, orally, QD. Participants continued receiving venetoclax at a dose of 400 mg, 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
	1.0; (0.12 to 3.66)	14.4; (9.81 to 20.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab Main Study, Venetoclax + Rituximab Main Study
	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 negative rates
	Estimated Value	13.41
	Confidence Interval	(2-Sided) 95%; 7.99 to 18.82
	Estimation Comments	The 95% CI was computed using Anderson-Hauck method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab Main Study, Venetoclax + Rituximab Main Study
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	16.28
	Confidence Interval	(2-Sided) 95%; 3.82 to 69.35
	Estimation Comments	OR was estimated using logistic regression model. The 95% CI was computed using Wald test.

23. Secondary Outcome

Title	Plasma Venetoclax Concentrations
Description	[Not Specified]
Time Frame	Pre-dose (0 hour, anytime before venetoclax administration) and 4 hours post-dose on D1 of Cycles 1 and 4; Cycle length = 28 days

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) evaluable population included all participants in the 'Venetoclax + Rituximab' arm 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 Main Study
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 once daily (QD) for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg, orally, QD. Participants continued receiving venetoclax at a dose of 400 mg, 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)

24. Secondary Outcome

Title	Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Core Symptom Severity, Module Symptom Severity, and Interference Scores
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

Outcome Measure Data

Analysis Population Description

Patient reported outcomes (PRO) evaluable population 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 Main Study	Venetoclax + Rituximab Main Study
Arm/Group Description:		Participants received bendamustine at a dose of 70 milligrams per meter square (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 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, orally, QD. Participants continued receiving venetoclax at a dose of 400 mg, 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
Description	EORTC QLQ-C30 is a validated self-report measure consisting of 30 questions incorporated into 5 functional scales (Physical, Role, Cognitive, Emotional, and Social), 3 symptom scales (fatigue, pain, nausea, and vomiting), 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'). Scores were averaged, transformed to 0-100 scale; where higher score for functional scales=poor level of functioning; 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

Outcome Measure Data

Analysis Population Description

Patient reported outcome (PRO) evaluable population 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 Main Study	Venetoclax + Rituximab Main Study
Arm/Group Description:		Participants received bendamustine at a dose of 70 milligrams per meter square (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 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, orally, QD. Participants continued receiving venetoclax at a dose of 400 mg, 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
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

Outcome Measure Data

Analysis Population Description

PRO evaluable population 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 Main Study	Venetoclax + Rituximab Main Study
Arm/Group Description:		Participants received bendamustine at a dose of 70 milligrams per meter square (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 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, orally, QD. Participants continued receiving venetoclax at a dose of 400 mg, 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. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	An AE was defined as any untoward medical occurrence in a participant administered with Mircera and which does not necessarily have a causal relationship with Mircera. A Serious Adverse Event (SAE) is any significant hazard, contraindication, side effect that is fatal or life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is medically significant or requires intervention to prevent one or other of the outcomes listed above. AEs were assessed using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI CTCAE, v4.0)
Time Frame	From signing of informed consent form up to approximately 8 years 5 months

Outcome Measure Data

Analysis Population Description

SE population included all randomized participants who received at least one dose of study treatment with participants grouped according to the actual treatment received.

Arm/Group Title	Bendamustine + Rituximab Main Study	Venetoclax + Rituximab Main Study
Arm/Group Description:	Participants received bendamustine at a dose of 70 milligrams per meter square (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 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, orally, QD. Participants continued receiving venetoclax at a dose of 400 mg, 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	188	194
Measure Type: Count of Participants; Unit of Measure: Participants
Adverse Events	185 98.4%	194 100.0%
Serious Adverse Events	84 44.7%	101 52.1%

28. Secondary Outcome

Title	Number of Participants With Grade 3 or Higher Tumor Lysis Syndrome (TLS) and Infusion-related Reactions (IRRs)
Description	An AE was defined as any untoward medical occurrence in a participant administered with Mircera and which does not necessarily have a causal relationship with Mircera. A SAE is any significant hazard, contraindication, side effect that is fatal or life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is medically significant or requires intervention to prevent one or other of the outcomes listed above. TLS and IRRs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe or medically significant; Grade 4 = Life-threatening; Grade 5 = Death. A higher grade indicates a worse outcome.
Time Frame	From signing of informed consent form up to approximately 8 years 5 months

Outcome Measure Data

Analysis Population Description

SE population included all randomized participants who received at least one dose of study treatment with participants grouped according to the actual treatment received.

Arm/Group Title	Bendamustine + Rituximab Main Study	Venetoclax + Rituximab Main Study
Arm/Group Description:	Participants received bendamustine at a dose of 70 milligrams per meter square (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 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, orally, QD. Participants continued receiving venetoclax at a dose of 400 mg, 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	188	194
Measure Type: Count of Participants; Unit of Measure: Participants
TLS	2 1.1%	6 3.1%
IRRs	10 5.3%	4 2.1%

29. Other Pre-specified Outcome

Title	Change From Baseline in Lymphocyte Subset Counts at Specified Time Points
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

30. Post-Hoc Outcome

Title	Euro QoL 5 Dimension (EQ-5D) Questionnaire Score
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

Adverse Events

Time Frame	From signing of informed consent form up to approximately 8 years 5 months
Adverse Event Reporting Description	SE population included all randomized participants who received at least one dose of study treatment with participants grouped according to the actual treatment received.
Arm/Group Title	Bendamustine + Rituximab Main Study		Venetoclax + Rituximab Main Study		Bendamustine + Rituximab Crossover Substudy		Venetoclax + Rituximab Re-Treatment Substudy
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.		Participants who entered the crossover substudy had a 5-week venetoclax dose ramp-up period to reach the target dose of 400 mg QD. Following the venetoclax ramp-up period, participants received 6 cycles of rituximab, 375 mg/m^2, as IV infusion on the Day 1 of each 28-day cycle. Participants who did not progress following the completion of the 6 cycles continued to receive venetoclax monotherapy until disease progression or for a maximum of 2 years from Cycle 1 crossover Day 1 of the substudy.		Participants who entered the re-treatment substudy had a 5-week venetoclax dose ramp-up period to reach the target dose of 400 mg QD. Following the venetoclax ramp-up period, participants received 6 cycles of rituximab consisting of a single infusion on the first day of each 28-day cycle. Participants who did not progress following the completion of the 6 cycles continued to receive venetoclax monotherapy until disease progression or for a maximum of 2 year from Cycle 1 re-treatment Day 1 of the substudy.
All-Cause Mortality
	Bendamustine + Rituximab Main Study		Venetoclax + Rituximab Main Study		Bendamustine + Rituximab Crossover Substudy		Venetoclax + Rituximab Re-Treatment Substudy
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	84/188 (44.68%)		60/194 (30.93%)		1/9 (11.11%)		8/25 (32.00%)
Serious Adverse Events
	Bendamustine + Rituximab Main Study		Venetoclax + Rituximab Main Study		Bendamustine + Rituximab Crossover Substudy		Venetoclax + Rituximab Re-Treatment Substudy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	84/188 (44.68%)		101/194 (52.06%)		5/9 (55.56%)		13/25 (52.00%)
Blood and lymphatic system disorders
Anaemia † 1	5/188 (2.66%)	6	3/194 (1.55%)	4	0/9 (0.00%)	0	1/25 (4.00%)	1
Autoimmune haemolytic anaemia † 1	3/188 (1.60%)	4	3/194 (1.55%)	3	0/9 (0.00%)	0	0/25 (0.00%)	0
Disseminated intravascular coagulation † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Febrile neutropenia † 1	16/188 (8.51%)	16	7/194 (3.61%)	7	0/9 (0.00%)	0	1/25 (4.00%)	1
Leukocytosis † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Neutropenia † 1	3/188 (1.60%)	3	3/194 (1.55%)	4	1/9 (11.11%)	1	0/25 (0.00%)	0
Pancytopenia † 1	0/188 (0.00%)	0	1/194 (0.52%)	2	0/9 (0.00%)	0	0/25 (0.00%)	0
Thrombocytopenia † 1	2/188 (1.06%)	2	2/194 (1.03%)	2	0/9 (0.00%)	0	0/25 (0.00%)	0
Immune thrombocytopenia † 1	0/188 (0.00%)	0	1/194 (0.52%)	2	0/9 (0.00%)	0	0/25 (0.00%)	0
Cardiac disorders
Acute myocardial infarction † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Angina pectoris † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Atrial fibrillation † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Cardiac failure † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Coronary artery disease † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Myocardial infarction † 1	0/188 (0.00%)	0	2/194 (1.03%)	2	0/9 (0.00%)	0	0/25 (0.00%)	0
Ventricular tachycardia † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Cardiac failure congestive † 1	0/188 (0.00%)	0	0/194 (0.00%)	0	0/9 (0.00%)	0	1/25 (4.00%)	1
Pericarditis † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Tachycardia † 1	0/188 (0.00%)	0	0/194 (0.00%)	0	0/9 (0.00%)	0	1/25 (4.00%)	1
Ear and labyrinth disorders
Deafness † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Vertigo † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Eye disorders
Eye haemorrhage † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Gastrointestinal disorders
Abdominal pain † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	1/9 (11.11%)	1	1/25 (4.00%)	1
Anal fistula † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Ascites † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Colitis † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Crohn's disease † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Diarrhoea † 1	0/188 (0.00%)	0	2/194 (1.03%)	2	0/9 (0.00%)	0	0/25 (0.00%)	0
Dyspepsia † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Gastrointestinal haemorrhage † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Nausea † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Oesophageal obstruction † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Small intestinal obstruction † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Vomiting † 1	1/188 (0.53%)	1	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
General disorders
Asthenia † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Hyperpyrexia † 1	1/188 (0.53%)	1	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Malaise † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Pyrexia † 1	13/188 (6.91%)	15	5/194 (2.58%)	5	0/9 (0.00%)	0	0/25 (0.00%)	0
Sudden cardiac death † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Sudden death † 1	1/188 (0.53%)	1	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Hepatobiliary disorders
Biliary obstruction † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Cholecystitis † 1	0/188 (0.00%)	0	0/194 (0.00%)	0	0/9 (0.00%)	0	1/25 (4.00%)	1
Jaundice cholestatic † 1	0/188 (0.00%)	0	0/194 (0.00%)	0	0/9 (0.00%)	0	1/25 (4.00%)	1
Infections and infestations
Abscess neck † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Appendicitis † 1	0/188 (0.00%)	0	2/194 (1.03%)	2	0/9 (0.00%)	0	0/25 (0.00%)	0
Atypical pneumonia † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Bronchitis † 1	2/188 (1.06%)	2	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Bronchopulmonary aspergillosis † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Campylobacter gastroenteritis † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Cellulitis † 1	1/188 (0.53%)	2	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Clostridium difficile colitis † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	1/25 (4.00%)	1
Cystitis † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Diverticulitis † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Erysipelas † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Escherichia sepsis † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Gastroenteritis rotavirus † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Gastroenteritis viral † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Haemophilus infection † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Hepatitis B † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Herpes simplex otitis externa † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Herpes zoster † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Influenza † 1	2/188 (1.06%)	2	3/194 (1.55%)	4	0/9 (0.00%)	0	0/25 (0.00%)	0
Listeria sepsis † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Localised infection † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Meningitis † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Moraxella infection † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Neutropenic sepsis † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Peritoneal tuberculosis † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Pharyngitis † 1	2/188 (1.06%)	2	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Pneumococcal bacteraemia † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Pneumocystis jirovecii pneumonia † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Pneumonia † 1	15/188 (7.98%)	17	19/194 (9.79%)	23	1/9 (11.11%)	2	3/25 (12.00%)	4
Pneumonia influenzal † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Pneumonia legionella † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Pneumonia streptococcal † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Respiratory tract infection † 1	0/188 (0.00%)	0	2/194 (1.03%)	2	0/9 (0.00%)	0	0/25 (0.00%)	0
Respiratory tract infection fungal † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Respiratory tract infection viral † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Rhinovirus infection † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	1/9 (11.11%)	1	0/25 (0.00%)	0
Scedosporium infection † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Sepsis † 1	4/188 (2.13%)	4	1/194 (0.52%)	1	1/9 (11.11%)	1	0/25 (0.00%)	0
Septic shock † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Sinusitis † 1	1/188 (0.53%)	1	2/194 (1.03%)	2	0/9 (0.00%)	0	0/25 (0.00%)	0
Staphylococcal infection † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Tooth abscess † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Upper respiratory tract infection † 1	2/188 (1.06%)	2	4/194 (2.06%)	4	0/9 (0.00%)	0	0/25 (0.00%)	0
Urinary tract infection † 1	1/188 (0.53%)	1	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Urinary tract infection pseudomonal † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Urosepsis † 1	1/188 (0.53%)	3	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Varicella zoster virus infection † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Viral infection † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Viral upper respiratory tract infection † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Lower respiratory tract infection † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Parainfluenzae virus infection † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Atypical mycobacterial infection † 1	0/188 (0.00%)	0	0/194 (0.00%)	0	0/9 (0.00%)	0	1/25 (4.00%)	1
COVID-19 † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	1/9 (11.11%)	1	1/25 (4.00%)	1
Gastroenteritis † 1	0/188 (0.00%)	0	0/194 (0.00%)	0	1/9 (11.11%)	1	0/25 (0.00%)	0
Pneumonia pseudomonal † 1	0/188 (0.00%)	0	0/194 (0.00%)	0	1/9 (11.11%)	2	0/25 (0.00%)	0
Injury, poisoning and procedural complications
Humerus fracture † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Infusion related reaction † 1	6/188 (3.19%)	8	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Tendon rupture † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Scar † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Ulna fracture † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Investigations
Body temperature increased † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Electrocardiogram QT prolonged † 1	0/188 (0.00%)	0	0/194 (0.00%)	0	1/9 (11.11%)	1	0/25 (0.00%)	0
Medical observation † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
SARS-CoV-2 test positive † 1	0/188 (0.00%)	0	0/194 (0.00%)	0	1/9 (11.11%)	1	0/25 (0.00%)	0
Metabolism and nutrition disorders
Decreased appetite † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Dehydration † 1	0/188 (0.00%)	0	2/194 (1.03%)	2	0/9 (0.00%)	0	0/25 (0.00%)	0
Diabetes mellitus † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Hyperkalaemia † 1	0/188 (0.00%)	0	2/194 (1.03%)	2	0/9 (0.00%)	0	0/25 (0.00%)	0
Hyperphosphataemia † 1	0/188 (0.00%)	0	2/194 (1.03%)	2	0/9 (0.00%)	0	0/25 (0.00%)	0
Tumour lysis syndrome † 1	1/188 (0.53%)	1	4/194 (2.06%)	4	0/9 (0.00%)	0	1/25 (4.00%)	1
Hypervolaemia † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Musculoskeletal chest pain † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Adenocarcinoma gastric † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Adenocarcinoma of colon † 1	1/188 (0.53%)	1	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Basal cell carcinoma † 1	0/188 (0.00%)	0	2/194 (1.03%)	3	0/9 (0.00%)	0	0/25 (0.00%)	0
Colon cancer † 1	1/188 (0.53%)	1	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Colorectal cancer † 1	0/188 (0.00%)	0	2/194 (1.03%)	2	0/9 (0.00%)	0	0/25 (0.00%)	0
Lung neoplasm malignant † 1	3/188 (1.60%)	3	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Lymphoma † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	1/25 (4.00%)	1
Malignant melanoma † 1	1/188 (0.53%)	1	2/194 (1.03%)	2	0/9 (0.00%)	0	0/25 (0.00%)	0
Medullary thyroid cancer † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Metastatic malignant melanoma † 1	1/188 (0.53%)	1	2/194 (1.03%)	3	0/9 (0.00%)	0	0/25 (0.00%)	0
Myelodysplastic syndrome † 1	1/188 (0.53%)	1	2/194 (1.03%)	2	0/9 (0.00%)	0	0/25 (0.00%)	0
Pancreatic carcinoma † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Prostate cancer † 1	1/188 (0.53%)	1	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Prostatic adenoma † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Squamous cell carcinoma † 1	1/188 (0.53%)	1	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Transitional cell carcinoma † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Breast cancer † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Colorectal adenocarcinoma † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Metastases to lung † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Metastasis † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Plasma cell myeloma † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Sebaceous adenoma † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Skin squamous cell carcinoma recurrent † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Squamous cell carcinoma of lung † 1	0/188 (0.00%)	0	0/194 (0.00%)	0	0/9 (0.00%)	0	1/25 (4.00%)	1
Squamous cell carcinoma of skin † 1	0/188 (0.00%)	0	3/194 (1.55%)	7	0/9 (0.00%)	0	0/25 (0.00%)	0
Nervous system disorders
Dizziness † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Haemorrhagic stroke † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Lacunar infarction † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Polyneuropathy † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Status epilepticus † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Syncope † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Renal and urinary disorders
Acute kidney injury † 1	1/188 (0.53%)	1	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Nephrolithiasis † 1	0/188 (0.00%)	0	1/194 (0.52%)	2	0/9 (0.00%)	0	0/25 (0.00%)	0
Renal impairment † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Chronic kidney disease † 1	0/188 (0.00%)	0	0/194 (0.00%)	0	0/9 (0.00%)	0	1/25 (4.00%)	1
Ureterolithiasis † 1	0/188 (0.00%)	0	0/194 (0.00%)	0	0/9 (0.00%)	0	1/25 (4.00%)	2
Reproductive system and breast disorders
Cervical dysplasia † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Uterine haemorrhage † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Bronchiectasis † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Lung disorder † 1	0/188 (0.00%)	0	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Pulmonary embolism † 1	1/188 (0.53%)	1	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Skin and subcutaneous tissue disorders
Dermatitis allergic † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Actinic keratosis † 1	0/188 (0.00%)	0	1/194 (0.52%)	2	0/9 (0.00%)	0	0/25 (0.00%)	0
Diabetic foot † 1	0/188 (0.00%)	0	0/194 (0.00%)	0	0/9 (0.00%)	0	1/25 (4.00%)	1
Vascular disorders
Aortic stenosis † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Deep vein thrombosis † 1	1/188 (0.53%)	1	1/194 (0.52%)	1	0/9 (0.00%)	0	0/25 (0.00%)	0
Hypotension † 1	5/188 (2.66%)	5	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
Haematoma † 1	0/188 (0.00%)	0	0/194 (0.00%)	0	0/9 (0.00%)	0	1/25 (4.00%)	1
Thrombosis † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	0/9 (0.00%)	0	0/25 (0.00%)	0
1 Term from vocabulary, MedDRA v25.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Bendamustine + Rituximab Main Study		Venetoclax + Rituximab Main Study		Bendamustine + Rituximab Crossover Substudy		Venetoclax + Rituximab Re-Treatment Substudy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	177/188 (94.15%)		190/194 (97.94%)		5/9 (55.56%)		9/25 (36.00%)
Blood and lymphatic system disorders
Anaemia † 1	40/188 (21.28%)	68	28/194 (14.43%)	48	1/9 (11.11%)	1	1/25 (4.00%)	1
Neutropenia † 1	84/188 (44.68%)	182	120/194 (61.86%)	290	3/9 (33.33%)	5	5/25 (20.00%)	13
Thrombocytopenia † 1	42/188 (22.34%)	57	23/194 (11.86%)	30	0/9 (0.00%)	0	2/25 (8.00%)	2
Febrile neutropenia † 1	3/188 (1.60%)	3	0/194 (0.00%)	0	1/9 (11.11%)	1	0/25 (0.00%)	0
Cardiac disorders
Supraventricular tachycardia † 1	1/188 (0.53%)	1	0/194 (0.00%)	0	1/9 (11.11%)	1	0/25 (0.00%)	0
Gastrointestinal disorders
Abdominal pain † 1	6/188 (3.19%)	7	13/194 (6.70%)	14	0/9 (0.00%)	0	0/25 (0.00%)	0
Constipation † 1	39/188 (20.74%)	47	27/194 (13.92%)	31	0/9 (0.00%)	0	0/25 (0.00%)	0
Diarrhoea † 1	31/188 (16.49%)	43	78/194 (40.21%)	120	0/9 (0.00%)	0	3/25 (12.00%)	4
Nausea † 1	64/188 (34.04%)	82	42/194 (21.65%)	58	0/9 (0.00%)	0	0/25 (0.00%)	0
Vomiting † 1	22/188 (11.70%)	29	15/194 (7.73%)	18	0/9 (0.00%)	0	0/25 (0.00%)	0
General disorders
Chills † 1	16/188 (8.51%)	20	8/194 (4.12%)	10	0/9 (0.00%)	0	1/25 (4.00%)	1
Fatigue † 1	39/188 (20.74%)	44	35/194 (18.04%)	41	0/9 (0.00%)	0	1/25 (4.00%)	1
Oedema peripheral † 1	7/188 (3.72%)	11	10/194 (5.15%)	14	0/9 (0.00%)	0	0/25 (0.00%)	0
Pyrexia † 1	33/188 (17.55%)	44	27/194 (13.92%)	41	0/9 (0.00%)	0	0/25 (0.00%)	0
Infections and infestations
Bronchitis † 1	13/188 (6.91%)	14	20/194 (10.31%)	32	0/9 (0.00%)	0	1/25 (4.00%)	1
Conjunctivitis † 1	5/188 (2.66%)	5	10/194 (5.15%)	11	0/9 (0.00%)	0	0/25 (0.00%)	0
Lower respiratory tract infection † 1	4/188 (2.13%)	4	11/194 (5.67%)	15	0/9 (0.00%)	0	0/25 (0.00%)	0
Nasopharyngitis † 1	11/188 (5.85%)	15	22/194 (11.34%)	29	0/9 (0.00%)	0	0/25 (0.00%)	0
Oral herpes † 1	12/188 (6.38%)	12	8/194 (4.12%)	11	0/9 (0.00%)	0	0/25 (0.00%)	0
Pharyngitis † 1	1/188 (0.53%)	1	14/194 (7.22%)	17	0/9 (0.00%)	0	1/25 (4.00%)	1
Sinusitis † 1	5/188 (2.66%)	5	19/194 (9.79%)	26	0/9 (0.00%)	0	0/25 (0.00%)	0
Upper respiratory tract infection † 1	28/188 (14.89%)	42	45/194 (23.20%)	81	0/9 (0.00%)	0	1/25 (4.00%)	1
Urinary tract infection † 1	7/188 (3.72%)	9	12/194 (6.19%)	22	0/9 (0.00%)	0	0/25 (0.00%)	0
Injury, poisoning and procedural complications
Infusion related reaction † 1	40/188 (21.28%)	54	16/194 (8.25%)	21	0/9 (0.00%)	0	0/25 (0.00%)	0
Investigations
Alanine aminotransferase increased † 1	10/188 (5.32%)	11	10/194 (5.15%)	17	0/9 (0.00%)	0	0/25 (0.00%)	0
Neutrophil count decreased † 1	13/188 (6.91%)	27	11/194 (5.67%)	27	1/9 (11.11%)	1	0/25 (0.00%)	0
Blood creatinine increased † 1	1/188 (0.53%)	1	5/194 (2.58%)	6	1/9 (11.11%)	2	0/25 (0.00%)	0
White blood cell count decreased † 1	3/188 (1.60%)	4	1/194 (0.52%)	1	1/9 (11.11%)	1	0/25 (0.00%)	0
Metabolism and nutrition disorders
Decreased appetite † 1	17/188 (9.04%)	18	8/194 (4.12%)	11	0/9 (0.00%)	0	0/25 (0.00%)	0
Hyperkalaemia † 1	0/188 (0.00%)	0	11/194 (5.67%)	16	0/9 (0.00%)	0	0/25 (0.00%)	0
Hypokalaemia † 1	7/188 (3.72%)	7	11/194 (5.67%)	12	1/9 (11.11%)	1	0/25 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	11/188 (5.85%)	15	17/194 (8.76%)	22	0/9 (0.00%)	0	0/25 (0.00%)	0
Back pain † 1	11/188 (5.85%)	11	14/194 (7.22%)	14	0/9 (0.00%)	0	0/25 (0.00%)	0
Muscle spasms † 1	11/188 (5.85%)	11	4/194 (2.06%)	4	0/9 (0.00%)	0	0/25 (0.00%)	0
Nervous system disorders
Dizziness † 1	11/188 (5.85%)	14	12/194 (6.19%)	14	0/9 (0.00%)	0	0/25 (0.00%)	0
Headache † 1	19/188 (10.11%)	21	21/194 (10.82%)	21	0/9 (0.00%)	0	0/25 (0.00%)	0
Psychiatric disorders
Insomnia † 1	12/188 (6.38%)	13	21/194 (10.82%)	22	0/9 (0.00%)	0	0/25 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Cough † 1	31/188 (16.49%)	37	36/194 (18.56%)	51	0/9 (0.00%)	0	0/25 (0.00%)	0
Dyspnoea † 1	14/188 (7.45%)	17	11/194 (5.67%)	14	0/9 (0.00%)	0	0/25 (0.00%)	0
Oropharyngeal pain † 1	7/188 (3.72%)	7	10/194 (5.15%)	12	0/9 (0.00%)	0	0/25 (0.00%)	0
Productive cough † 1	4/188 (2.13%)	5	12/194 (6.19%)	14	0/9 (0.00%)	0	0/25 (0.00%)	0
Skin and subcutaneous tissue disorders
Pruritus † 1	9/188 (4.79%)	9	10/194 (5.15%)	11	0/9 (0.00%)	0	1/25 (4.00%)	1
Rash † 1	25/188 (13.30%)	29	15/194 (7.73%)	19	0/9 (0.00%)	0	0/25 (0.00%)	0
Dermatitis † 1	0/188 (0.00%)	0	5/194 (2.58%)	5	1/9 (11.11%)	1	0/25 (0.00%)	0
Vascular disorders
Hypertension † 1	7/188 (3.72%)	7	15/194 (7.73%)	15	0/9 (0.00%)	0	0/25 (0.00%)	0
1 Term from vocabulary, MedDRA v25.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

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

• Name/Title: Medical Communications
• Organization: Hoffmann-La Roche
• Phone: 800-821-8590
• EMail: genentech@druginfo.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Badawi M, Chen X, Marroum P, Suleiman AA, Mensing S, Koenigsdorfer A, Schiele JT, Palenski T, Samineni D, Hoffman D, Menon R, Salem AH. Bioavailability Evaluation of Venetoclax Lower-Strength Tablets and Oral Powder Formulations to Establish Interchangeability with the 100 mg Tablet. Clin Drug Investig. 2022 Aug;42(8):657-668. doi: 10.1007/s40261-022-01172-4. Epub 2022 Jul 13.

Seymour JF, Kipps TJ, Eichhorst BF, D'Rozario J, Owen CJ, Assouline S, Lamanna N, Robak T, de la Serna J, Jaeger U, Cartron G, Montillo M, Mellink C, Chyla B, Panchal A, Lu T, Wu JQ, Jiang Y, Lefebure M, Boyer M, Kater AP. Enduring undetectable MRD and updated outcomes in relapsed/refractory CLL after fixed-duration venetoclax-rituximab. Blood. 2022 Aug 25;140(8):839-850. doi: 10.1182/blood.2021015014.

Kater AP, Wu JQ, Kipps T, Eichhorst B, Hillmen P, D'Rozario J, Assouline S, Owen C, Robak T, de la Serna J, Jaeger U, Cartron G, Montillo M, Dubois J, Eldering E, Mellink C, Van Der Kevie-Kersemaekers AM, Kim SY, Chyla B, Punnoose E, Bolen CR, Assaf ZJ, Jiang Y, Wang J, Lefebure M, Boyer M, Humphrey K, Seymour JF. Venetoclax Plus Rituximab in Relapsed Chronic Lymphocytic Leukemia: 4-Year Results and Evaluation of Impact of Genomic Complexity and Gene Mutations From the MURANO Phase III Study. J Clin Oncol. 2020 Dec 1;38(34):4042-4054. doi: 10.1200/JCO.20.00948. Epub 2020 Sep 28.

Kater AP, Seymour JF, Hillmen P, Eichhorst B, Langerak AW, Owen C, Verdugo M, Wu J, Punnoose EA, Jiang Y, Wang J, Boyer M, Humphrey K, Mobasher M, Kipps TJ. Fixed Duration of Venetoclax-Rituximab in Relapsed/Refractory Chronic Lymphocytic Leukemia Eradicates Minimal Residual Disease and Prolongs Survival: Post-Treatment Follow-Up of the MURANO Phase III Study. J Clin Oncol. 2019 Feb 1;37(4):269-277. doi: 10.1200/JCO.18.01580. Epub 2018 Dec 3.

Seymour JF, Kipps TJ, Eichhorst B, Hillmen P, D'Rozario J, Assouline S, Owen C, Gerecitano J, Robak T, De la Serna J, Jaeger U, Cartron G, Montillo M, Humerickhouse R, Punnoose EA, Li Y, Boyer M, Humphrey K, Mobasher M, Kater AP. Venetoclax-Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia. N Engl J Med. 2018 Mar 22;378(12):1107-1120. doi: 10.1056/NEJMoa1713976.

Jones AK, Freise KJ, Agarwal SK, Humerickhouse RA, Wong SL, Salem AH. Clinical Predictors of Venetoclax Pharmacokinetics in Chronic Lymphocytic Leukemia and Non-Hodgkin's Lymphoma Patients: a Pooled Population Pharmacokinetic Analysis. AAPS J. 2016 Sep;18(5):1192-1202. doi: 10.1208/s12248-016-9927-9. Epub 2016 May 27.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02005471
• 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: October 17, 2023