MURANO: 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)

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02005471
• Collaborator: AbbVie (Industry)

Study Details

Study Description

Brief Summary

The purpose of this open-label, multicenter, randomized, Phase III study is to evaluate the benefit of venetoclax in combination with rituximab compared with bendamustine in combination with rituximab in participants with relapsed or refractory CLL. Participants will be randomly assigned in 1:1 ratio to receive either venetoclax + rituximab (Arm A) or bendamustine + rituximab (Arm B).

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia	Drug: Bendamustine; Drug: Venetoclax; Drug: Rituximab	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 389 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Phase III, Open-Label, Randomized Study in Relapsed/Refractory Patients With Chronic Lymphocytic Leukemia to Evaluate the Benefit of Venetoclax (GDC-0199/ABT-199) Plus Rituximab Compared With Bendamustine Plus Rituximab
• Actual Study Start Date: Mar 17, 2014
• Actual Primary Completion Date: May 8, 2017
• Anticipated Study Completion Date: Jun 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Bendamustine + Rituximab Participants will receive bendamustine 70 milligrams per meter squared (mg/m^2) via intravenous (IV) infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 followed by 500 mg/m^2 on Day 1 of Cycles 2-6.	Drug: Bendamustine; Bendamustine will be administered at a dose of 70 mg/m^2 via IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.; Drug: Rituximab; Rituximab will be administered 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. R/C Substudy: Following the venetoclax ramp-up period, rituximab will be administered for 6 cycles consisting of a single infusion on the first day of each 28-day cycle.
Experimental: Venetoclax + Rituximab Participants will be initially placed on a venetoclax 5 weeks ramp-up period, and will receive an initial dose of 20 milligrams (mg) via tablet orally once daily (QD). Then the dose will be incremented weekly up to a maximum dose of 400 mg. Participants will then continue receiving venetoclax 400 mg QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards, as directed by the investigator, in combination with rituximab 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 followed by 500 mg/m^2 on Day 1 of Cycles 2-6.	Drug: Venetoclax; Venetoclax will be administered at an initial dose of 20 mg via tablet orally QD, incremented weekly up to a maximum dose of 400 mg during a 5-week ramp-up period. Venetoclax will be continued at 400 mg QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to disease progression (PD) or 2 years, whichever occurs first. R/C Substudy: venetoclax will be administered for 5-week dose ramp-up period to reach the target dose of 400 mg QD. Venetoclax will continue to be administered during the rituximab cycles until disease progression or for a maximum of 2 years from Cycle 1R/C Day 1 of the R/C Substudy.; Other Names: GDC-0199, ABT-199 ; Drug: Rituximab; Rituximab will be administered 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. R/C Substudy: Following the venetoclax ramp-up period, rituximab will be administered for 6 cycles consisting of a single infusion on the first day of each 28-day cycle.
Experimental: Bendamustine + Rituximab Crossover Substudy Participants entering the Crossover Substudy will have a 5-week venetoclax dose ramp-up period to reach the target dose of 400 mg QD. Following the venetoclax ramp-up period, Participants will receive 6 cycles of rituximab consisting of a single infusion on the first day of each 28-day cycle. Participants will continue to take their daily dose of venetoclax during the rituximab cycles. Participants who have not progressed following the completion of the 6 cycles will continue to receive venetoclax monotherapy until disease progression or for a maximum of 2 years from Cycle 1 Crossover Day 1 of the Substudy.	Drug: Venetoclax; Venetoclax will be administered at an initial dose of 20 mg via tablet orally QD, incremented weekly up to a maximum dose of 400 mg during a 5-week ramp-up period. Venetoclax will be continued at 400 mg QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to disease progression (PD) or 2 years, whichever occurs first. R/C Substudy: venetoclax will be administered for 5-week dose ramp-up period to reach the target dose of 400 mg QD. Venetoclax will continue to be administered during the rituximab cycles until disease progression or for a maximum of 2 years from Cycle 1R/C Day 1 of the R/C Substudy.; Other Names: GDC-0199, ABT-199 ; Drug: Rituximab; Rituximab will be administered 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. R/C Substudy: Following the venetoclax ramp-up period, rituximab will be administered for 6 cycles consisting of a single infusion on the first day of each 28-day cycle.
Experimental: Venetoclax + Rituximab Re-Treatment Participants entering the Re-Treatment Substudy will have a 5-week venetoclax dose ramp-up period to reach the target dose of 400 mg QD. Following the venetoclax ramp-up period, Participants will receive 6 cycles of rituximab consisting of a single infusion on the first day of each 28-day cycle. Participants will continue to take their daily dose of venetoclax during the rituximab cycles. Participants who have not progressed following the completion of the 6 cycles will continue to receive venetoclax monotherapy until disease progression or for a maximum of 2 years from Cycle 1 Re-Treatment Day 1 of the Substudy.	Drug: Venetoclax; Venetoclax will be administered at an initial dose of 20 mg via tablet orally QD, incremented weekly up to a maximum dose of 400 mg during a 5-week ramp-up period. Venetoclax will be continued at 400 mg QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to disease progression (PD) or 2 years, whichever occurs first. R/C Substudy: venetoclax will be administered for 5-week dose ramp-up period to reach the target dose of 400 mg QD. Venetoclax will continue to be administered during the rituximab cycles until disease progression or for a maximum of 2 years from Cycle 1R/C Day 1 of the R/C Substudy.; Other Names: GDC-0199, ABT-199 ; Drug: Rituximab; Rituximab will be administered 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. R/C Substudy: Following the venetoclax ramp-up period, rituximab will be administered for 6 cycles consisting of a single infusion on the first day of each 28-day cycle.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With PD as Assessed by the Investigator Using Standard International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Guidelines or Death [Baseline up to PD or death from any cause, whichever occurred first (up to approximately 3 years)]

   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.

2. Progression-Free Survival (PFS) as Assessed by the Investigator Using Standard iwCLL Guidelines [Baseline up to PD or death, whichever occurred first (up to approximately 3 years)]

   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.

Secondary Outcome Measures

1. Percentage of Participants With PD or Death as Assessed by the Independent Review Committee (IRC) Using Standard iwCLL Guidelines [Baseline up to PD or death, whichever occurred first (up to approximately 3 years)]

   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.

2. PFS as Assessed by the IRC Using Standard iwCLL Guidelines [Baseline up to PD or death, whichever occurred first (up to approximately 3 years)]

   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.

3. 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 [Baseline up to PD or death, whichever occurred first (up to approximately 3 years)]

   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.

4. PFS as Assessed by the Investigator Using Standard iwCLL Guidelines in Participants With 17p Deletion as Identified by FISH Test [Baseline up to PD or death, whichever occurred first (up to approximately 3 years)]

   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.

5. 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 [Baseline up to PD or death, whichever occurred first (up to approximately 3 years)]

   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.

6. PFS as Assessed by the IRC Using Standard iwCLL Guidelines in Participants With 17p Deletion as Identified by FISH Test [Baseline up to PD or death, whichever occurred first (up to approximately 3 years)]

   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.

7. 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 [Baseline up to last follow-up visit (FUV) (maximum up to data cut-off date, overall approximately 3 years)]

   Response was assessed by the investigator according to the iwCLL guidelines and was confirmed by repeat assessment >/=4 weeks after initial documentation. CR: peripheral blood lymphocytes <4000/mcL; absence of any new lesion, nodal disease, lymphadenopathy, hepatomegaly, splenomegaly, and constitutional symptoms; neutrophils >1500/mcL, platelets >100000/mcL, hemoglobin >11.0 g/dL without need for transfusion or exogenous growth factors; normocellular bone marrow with <30% lymphocytes; no lymphoid nodules. CRi: fulfilling all CR criteria but persistent cytopenia. PR: >/=50% reduction in two of the following: peripheral blood lymphocytes, lymphadenopathy, spleen and/or liver enlargement; and one of the following: neutrophils >1500/mcL, platelets >100000/mcL, hemoglobin >11.0 g/dL or >/=50% improvement without need for transfusion or exogenous growth factors. nPR: fulfilling all CR criteria but presence of lymphoid nodules. The 95% CI was computed using Pearson-Clopper method.

8. Percentage of Participants With Best Overall Response of CR, CRi, nPR, or PR as Assessed by the IRC Using iwCLL Guidelines [Baseline up to last FUV (maximum up to data cut-off date, overall approximately 3 years)]

   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.

9. 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 [End of combination treatment response (EoCTR) visit (8 to 12 weeks after Cycle [C] 6 Day [1]); Cycle length = 28 days]

   Response was assessed by the investigator according to the iwCLL guidelines and was confirmed by repeat assessment >/=4 weeks after initial documentation. CR: peripheral blood lymphocytes <4000/mcL; absence of any new lesion, nodal disease, lymphadenopathy, hepatomegaly, splenomegaly, and constitutional symptoms; neutrophils >1500/mcL, platelets >100000/mcL, hemoglobin >11.0 g/dL without need for transfusion or exogenous growth factors; normocellular bone marrow with <30% lymphocytes; no lymphoid nodules. CRi: fulfilling all CR criteria but persistent cytopenia. PR: >/=50% reduction in two of the following: peripheral blood lymphocytes, lymphadenopathy, spleen and/or liver enlargement; and one of the following: neutrophils >1500/mcL, platelets >100000/mcL, hemoglobin >11.0 g/dL or >/=50% improvement without need for transfusion or exogenous growth factors. nPR: fulfilling all CR criteria but presence of lymphoid nodules. The 95% CI was computed using Pearson-Clopper method.

10. 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 [EoCTR visit (8 to 12 weeks after C6D1); Cycle length = 28 days]

    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.

11. Percentage of Participants Who Died [Baseline up to last FUV (maximum up to Data Cut-off date, overall approximately 3 years)]

    Percentage of participants who died from any cause, during the study, was reported.

12. Overall Survival (OS) [Baseline up to last FUV (maximum up to Data Cut-off date, overall approximately 3 years)]

    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.

13. 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 [Baseline up to PD/relapse, start of a new anti-CLL therapy, or death from any cause, whichever occurred first (maximum up to Data Cut-off date, overall approximately 3 years)]

    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.

14. Event-Free Survival (EFS) as Assessed by the Investigator Using iwCLL Guidelines [Baseline up to PD/relapse, start of a new anti-CLL therapy, or death from any cause, whichever occurred first (maximum up to Data Cut-off date, overall approximately 3 years)]

    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.

15. 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 [From time of achieving best overall response until PD or death from any cause, whichever occurred first (up to approximately 3 years)]

    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.

16. Duration of Responses (DOR) as Assessed by the Investigator Using iwCLL Guidelines [From time of achieving best overall response until PD or death from any cause, whichever occurred first (up to approximately 3 years)]

    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.

17. Percentage of Participants With Start of New Anti-CLL Treatment or Death as Assessed by the Investigator [Baseline up to start of new ani-CLL therapy or death, whichever occurred first (up to approximately 3 years)]

    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.

18. Time to New Anti-CLL Treatment (TTNT) as Assessed by the Investigator [Baseline up to start of new ani-CLL therapy or death, whichever occurred first (up to approximately 3 years)]

    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.

19. Percentage of Participants With Minimal Residual Disease (MRD) Negativity at the EoCTR Visit [EoCTR visit (8 to 12 weeks after C6D1); Cycle length = 28 days]

    MRD-negativity was defined as the presence of <1 malignant B-cell per 10000 normal B-cells in a sample of at least 200000 B-cells, as assessed by the allele specific oligonucleotide polymerase chain reaction (ASO-PCR) and/or flow cytometry technique. Percentage of participants with MRD-negativity at the EoCTR visit was reported. The 95% CI was computed using Pearson-Clopper method.

20. Plasma Venetoclax Concentrations [Pre-dose (0 hour, anytime before venetoclax administeration) and 4 hours post-dose on D1 of Cycles 1 and 4; Cycle length = 28 days]

21. Change From Baseline in Lymphocyte Subset Counts at Specified Time Points [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]

22. Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Core Symptom Severity, Module Symptom Severity, and Interference Scores [Baseline, Days 1, 8, and 15 of Cycles 1, 2, and 3; Cycle length = 28 days]

    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).

23. 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 [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]

    The EORTC QLQ-C30 is a validated self-report measure consisting of 30 questions incorporated into five functional scales (Physical, Role, Cognitive, Emotional, and Social scales), three symptom scales (fatigue, pain, nausea, and vomiting scales), a global health status/global QoL scale, and single items (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea). Most questions used 4-point scale (1='Not at all' to 4='Very much'), while 2 questions used 7-point scale (1='very poor' to 7='Excellent'). Functional scales score and global health status/global QoL scale score are reported. Scores were averaged, transformed to 0-100 scale; where higher score for functional scales = poor level of functioning and higher score for global health status/global QoL = better HRQoL.

24. Change From Baseline in HRQoL as Measured by Quality of Life Questionnaire Associated CLL Module (QLQ-CLL16) Multi-Item Scales Score [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]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of CLL per diagnostic criteria for relapsed or refractory CLL per the international workshop on chronic lymphocytic leukemia (iwCLL) guidelines

• Previously treated with 1-3 lines of therapy (example: completed greater than or equal to [>/=] 2 treatment cycles per therapy), including at least one standard chemotherapy-containing regimen

• Participants previously treated with bendamustine only if their duration of response was >/= 24 months

• Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to (</=) 1

• Adequate bone marrow function

• Adequate renal and hepatic function

• Participants must use effective birth control throughout study until at least 30 days after study treatment or 1 year after rituximab treatment, whichever is later; female participants must not be pregnant or breast-feeding

• For participants with the 17p deletion, previously treated with 1-3 lines of therapy, including at least one prior standard chemotherapy-containing regimen or at least one prior alemtuzumab-containing therapy

Inclusion Criteria R/C Substudy:

• Participants randomized to Arm A or Arm B with a confirmed disease progression of CLL per iwCLL criteria

• Participants who have not received new anti-CLL therapy following disease progression in Arm A or Arm B

• Adequate renal and hepatic function per laboratory reference range

Exclusion Criteria:

• Transformation of CLL to aggressive non-Hodgkin lymphoma or central nervous system (CNS) involvement by CLL

• Undergone an allogenic stem cell transplant

• A history of significant renal, neurologic, psychiatric, endocrine, metabolic, immunologic, cardiovascular or hepatic disease

• Hepatitis B or C or known human immunodeficiency virus (HIV) positive

• Receiving warfarin treatment

• Received an anti-CLL monoclonal antibody within 8 weeks prior to the first dose of study drug

• Received any anti-cancer or investigational therapy within 28 days prior to the first dose of study drug or has not recovered to less than Grade 2 clinically significant adverse effect(s)/toxicity(ies) of any previous therapy

• Received cytochrome P450 3A4 (CYP3A4) inhibitors (such as fluconazole, ketoconazole and clarithromycin) or inducers (such as rifampin, carbamazapine, phenytoin, St. John's Wort) within 7 days prior to the first dose of venetoclax

• History of prior venetoclax treatment

• Participants with another cancer, history of another cancer considered uncured on in complete remission for <5 years, or currently under treatment for another suspected cancer except non-melanoma skin cancer or carcinoma in situ of the cervix that has been treated or excised and is considered resolved

• Malabsorption syndrome or other condition that precludes enteral route of administration

• Other clinically significant uncontrolled condition(s) including, but not limited to, systemic infection (viral, bacterial or fungal)

• Vaccination with a live vaccine within 28 days prior to randomization

• Consumed grapefruit or grapefruit products, seville oranges (including marmalade containing seville oranges), or star fruit within 3 days prior to the first dose of study treatment

• A cardiovascular disability status of New York Heart Association Class >/=3. Class 3 is defined as cardiac disease in which participants are comfortable at rest but have marked limitation of physical activity due to fatigue, palpitations, dyspnea, or anginal pain

• Major surgery within 30 days prior to the first dose of study treatment

• A participant who is pregnant or breastfeeding

• Known allergy to both xanthine oxidase inhibitors and rasburicase

Exclusion Criteria R/C Substudy:

• Transformation of CLL to aggressive NHL (e.g., Richter's transformation, prolymphocytic leukemia, or DLBCL) or CNS involvement by CLL

• Evidence of other clinically significant uncontrolled condition(s) including, but not limited to, uncontrolled systemic infection (viral, bacterial, or fungal)

• Development of other malignancy since enrollment into the study, with the exception of curatively treated basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix

• Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia

• History of severe (i.e., requiring permanent discontinuation of prior rituximab therapy) prior allergic or anaphylactic reactions to rituximab

• Known HIV positivity

• Positive test results for chronic hepatitis B infection (defined as positive hepatitis B surface antigen [HbsAg] serology)

• Positive test results for hepatitis C virus (HCV; HCV antibody serology testing)

• Requires the use of warfarin (due to potential drug interactions that may potentially increase the exposure of warfarin)

• Has not recovered to less than Grade 2 clinically significant adverse effect(s)/toxicity(ies) of any previous therapy

• Received potent CYP3A4 inhibitors (such as fluconazole, ketoconazole, and clarithromycin) within 7 days prior to the first dose of study treatment

• Received potent CYP3A4 inducers (such as rifampin, carbamazepine, phenytoin, St. John's wort) within 7 days prior to the first dose of study treatment

• Consumed grapefruit or grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to the first dose of study treatment

• A cardiovascular disability status of New York Heart Association Class >/= 3

• A significant history of renal, neurologic, psychiatric, endocrine, metabolic, immunologic, cardiovascular, or hepatic disease that, in the opinion of the investigator, would adversely affect the participants's participation in this study or interpretation of study outcomes

• Major surgery within 30 days prior to the first dose of study treatment

• A participant who is pregnant or breastfeeding

• Malabsorption syndrome or other condition that precludes enteral route of administration

• Known allergy to both xanthine oxidase inhibitors and rasburicase

• Vaccination with a live vaccine within 28 days prior to randomization

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California San Diego Medical Center	La Jolla	California	United States	92093-5354
2	Henry Ford Health System	Detroit	Michigan	United States	48202
3	Memorial Sloan Kettering Cancer Center; Clinical Trials Office	New York	New York	United States	10021
4	Perlmutter Cancer Center NYU Langone Health	New York	New York	United States	10032
5	Huntsman Cancer Institute; University of Utah	Salt Lake City	Utah	United States	84112
6	The Canberra Hospital	Garran	Australian Capital Territory	Australia	2065
7	Concord Repatriation General Hospital	Concord	New South Wales	Australia	2139
8	St George Hospital	Kogarah, New South Wales	New South Wales	Australia	2217
9	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
10	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
11	Flinders Medical Centre	Bedford Park	South Australia	Australia	5042
12	Royal Hobart Hospital	Hobart	Tasmania	Australia	7000
13	Peter MacCallum Cancer Center	East Melbourne	Victoria	Australia	3002
14	Frankston Hospital	Frankston	Victoria	Australia	3199
15	Monash Medical Centre; Haematology	Melbourne	Victoria	Australia	3168
16	Slade Health Pharmacy	Mount Waverley	Victoria	Australia	3149
17	Royal Melbourne Hospital	Parkville	Victoria	Australia	3050
18	The Perth Blood Institute	Nedlands	Western Australia	Australia	6009
19	Medizinische Universität Innsbruck	Innsbruck		Austria	6020
20	LKH - Universitätsklinikum der PMU Salzburg	Salzburg		Austria	5020
21	Medizinische Universität Wien	Wien		Austria	1090
22	Klinik Ottakring	Wien		Austria	1160
23	ZNA Antwerpen; Department Hematology	Antwerpen		Belgium	2060
24	Cliniques Universitaires Saint-Luc; Hematology	Bruxelles		Belgium	1200
25	AZ Groeninge	Kortrijk		Belgium	8500
26	UZ Leuven; Department Hematology	Leuven		Belgium	3000
27	CHU UCL Mont-Godinne	Mont-godinne		Belgium	5530
28	AZ Delta (Campus Rumbeke)	Roeselare		Belgium	8800
29	Foothills Medical Centre; Centre Dept of Medical Clinical Neuroscience	Calgary	Alberta	Canada	T2N 2T9
30	Juravinski Cancer Clinic	Hamilton	Ontario	Canada	L8N 3Z5
31	Jewish General Hospital	Montreal	Quebec	Canada	H3T 1E2
32	Saskatoon City Hospital;Saskatchewan Cancer Centre	Saskatoon	Saskatchewan	Canada	S7N 4H4
33	Fakultni nemocnice Brno	Brno		Czechia	613 00
34	Fakultni nemocnice Hradec Kralove	Hradec Kralove		Czechia	500 05
35	Fakultní nemocnice Olomouc	Olomouc		Czechia	775 20
36	Fakultni nemocnice Ostrava	Ostrava - Poruba		Czechia	708 52
37	Vseobecna fakultni nemocnice v Praze	Praha 2		Czechia	128 08
38	Fakultni nemocnice Kralovske Vinohrady	Praha		Czechia	100 34
39	Herlev Hospital	Herlev		Denmark	2730
40	Rigshospitalet	København Ø		Denmark	2100
41	Odense Universitetshospital	Odense C		Denmark	5000
42	Sjællands Universitetshospital, Roskilde	Roskilde		Denmark	4000
43	Sygehus Lillebælt, Vejle	Vejle		Denmark	7100
44	Hôpital Morvan	Brest		France	29609
45	Centre Hospitalier Départemental Les Oudairies	La Roche sur Yon		France	85025
46	Hopital Claude Huriez - CHU Lille	Lille		France	59037
47	Hopital Saint Eloi	Montpellier		France	34295
48	CHU Nantes - Hôtel Dieu; Service Assistance Medicale à la Procreation	Nantes		France	44093
49	Hopital Robert Debre	Paris		France	75019
50	Centre Hospitalier Lyon Sud	Pierre Benite		France	69495
51	CHU Poitiers - Hopital La Miletrie	Poitiers		France	86000
52	CHU de Rennes - Hopital de Pontchaillo	Rennes		France	35033
53	Centre Henri Becquerel	Rouen		France	76038
54	Institut Universitaire du Cancer - Oncopole Toulouse (IUCT-O)	Toulouse		France	31059
55	CHU Tours - Hôpital Bretonneau	Tours		France	37044
56	Hôpital de Brabois Adultes	Vandoeuvre-les-nancy		France	54511
57	Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden	Dresden		Germany	01307
58	Universitaetsklinikum Freiburg	Freiburg		Germany	79106
59	Universitätsklinikum Tübingen	Tuebingen		Germany	72076
60	Semmelweis Egyetem	Budapest		Hungary	1083
61	Orszagos Onkologiai Intezet	Budapest		Hungary	1122
62	Debreceni Egyetem Klinikai Központ; Bőrgyógyászati Klinika	Debrecen		Hungary	4012
63	Somogy Megyei Kaposi Mor Oktato Korhaz	Pecs		Hungary	7624
64	Szegedi Tud.Egyetem Szent-Gyorgyi Albert Klin.Kozp.	Szeged		Hungary	6720
65	Azienda Ospedaliera Città della Salute e della Scienza di Torino; Radiology	Torino	Abruzzo	Italy	10126
66	Azienda Ospedaliero Universitaria San Martino	Genova	Liguria	Italy	16132
67	Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)	Bergamo	Lombardia	Italy	24127
68	Ospedale San Raffaele	Milano	Lombardia	Italy	20132
69	Asst Grande Ospedale Metropolitano Niguarda; SC Farmacia Ospedale	Milano	Lombardia	Italy	20162
70	Azienda Ospedaliero Universitaria Ospedali Riuniti	Torrette Di Ancona	Marche	Italy	60126
71	Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico Bari	Bari	Puglia	Italy	70124
72	Azienda Ospedaliera Universitaria Careggi	Firenze	Toscana	Italy	50141
73	Azienda Ospedaliera Di Padova	Padova	Veneto	Italy	35128
74	Seoul National University Bundang Hospital	Seongnam-si		Korea, Republic of	13605
75	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
76	Konkuk University Medical Center	Seoul		Korea, Republic of	05030
77	The Catholic University of Korea Seoul St. Mary's Hospital	Seoul		Korea, Republic of	137-701
78	Amsterdam UMC, Locatie VUMC; Neurology	Amsterdam		Netherlands	1081 HV
79	Amsterdam UMC Location AMC	Amsterdam		Netherlands	1105 AZ
80	Albert Schweitzer Ziekenhuis, Dordwijk; Internal Medicine, Hemato-Oncology	Dordrecht		Netherlands	3318 AT
81	Medisch Spectrum Twente	Enschede		Netherlands	7512 KZ
82	Leids Universitair Medisch Centrum; Cardiology	Leiden		Netherlands	2333 ZA
83	Erasmus Medisch Centrum Rotterdam; Lokatie Daniel den Hoed	Rotterdam		Netherlands	3015 GD
84	UMC Utrecht	Utrecht		Netherlands	3508 GA
85	North Shore Hospital; Haematolgy	Auckland		New Zealand	1309
86	Middlemore Hospital	Auckland		New Zealand
87	Christchurch Hospital NZ	Christchurch		New Zealand	8011
88	Baxter Healthcare	Mount Wellington		New Zealand	1060
89	SP ZOZ Zespol Szpitali Miejskich w Chorzowie	Chorzow		Poland	41-500
90	Uniwersyteckie Centrum Kliniczne	Gdansk		Poland	80-214
91	Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi	Lodz		Poland	93-513
92	Szpital Wojewodzki w Opolu	Opole		Poland	45-061
93	MTZ Clinical Research Sp. z o.o.	Warszawa		Poland	02-106
94	Samodzielny Publiczny Szpital Kliniczny nr 1	Zabrze		Poland	44803
95	Kemerovo Regional Clinical Hospital	Kemerovo		Russian Federation	650066
96	FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"	Moscow		Russian Federation	115478
97	BHI of Omsk region Clinical Oncology Dispensary	Omsk		Russian Federation	644013
98	SRI of Hematology and Transfusiology	St. Petersburg		Russian Federation	191024
99	North-West Federal Medical Research Center n.a. V.A. Almazov	St. Petersburg		Russian Federation	197341
100	Complejo Hospitalario de Navarra	Pamplona	Navarra	Spain	31008
101	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
102	Hospital Clinic i Provincial de Barcelona; Hematology	Barcelona		Spain	08036
103	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
104	Hospital Clinico Universitario de Salamanca	Salamanca		Spain	37007
105	Skånes Universitetssjukhus	Lund		Sweden	221 85
106	Akademiska Sjukhuset	Uppsala		Sweden	751 85
107	National Taiwan University Hospital	Taipei		Taiwan	10002
108	Bristol Haematology and Oncology Centre	Bristol		United Kingdom	BS2 8ED
109	The Christie	Manchester		United Kingdom	M20 4BX
110	Southampton General Hospital	Southampton		United Kingdom	SO16 6YD
111	Singleton Hospital; Pharmacy Department	Swansea		United Kingdom	SA2 8QA

Sponsors and Collaborators

• Hoffmann-La Roche
• AbbVie

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol - Nov 21, 2016
• Statistical Analysis Plan - May 18, 2017

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02005471
• Other Study ID Numbers: GO28667; 2013-002110-12
• First Posted: Dec 9, 2013
• Last Update Posted: Nov 11, 2021
• Last Verified: Nov 1, 2021

• Additional relevant MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Rituximab; Bendamustine Hydrochloride; Venetoclax

Study Results

Participant Flow

Recruitment Details	A total of 489 participants were screened, out of which, 389 participants were enrolled into the study.

Arm/Group Title	Bendamustine + Rituximab	Venetoclax + Rituximab
Arm/Group Description	Participants received bendamustine at a dose of 70 milligrams per meter squared (mg/m^2) via intravenous (IV) infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.	Participants were initially placed on a venetoclax ramp-up period of 5 weeks, and received an initial dose of 20 milligrams (mg) via tablet orally once daily (QD) for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to disease progression (PD) or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Period Title: Overall Study
STARTED	195	194
Treated	188	194
COMPLETED	0	0
NOT COMPLETED	195	194

Baseline Characteristics

Arm/Group Title	Bendamustine + Rituximab	Venetoclax + Rituximab	Total
Arm/Group Description	Participants received bendamustine at a dose of 70 mg/m^2 via IV infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.	Participants were initially placed on a venetoclax ramp-up period of 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.	Total of all reporting groups
Overall Participants	195	194	389
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.4 (9.6)	63.9 (10.5)	64.1 (10.1)
Sex: Female, Male (Count of Participants)
Female	44 22.6%	58 29.9%	102 26.2%
Male	151 77.4%	136 70.1%	287 73.8%
Ethnicity (NIH/OMB) (Count of 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) (Count of Participants)
American Indian or Alaska Native	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%
Black or African American	2 1%	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%
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.
Time Frame	Baseline up to PD or death from any cause, whichever occurred first (up to approximately 3 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Bendamustine + Rituximab	Venetoclax + Rituximab
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.
Measure Participants	195	194
Number [percentage of participants]	58.5 30%	16.5 8.5%

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 3 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Bendamustine + Rituximab	Venetoclax + Rituximab
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.
Measure Participants	195	194
Median (95% Confidence Interval) [months]	17.0	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab, Venetoclax + Rituximab
	Comments	Stratified Analysis; Stratification factors: 17p deletion, risk status, geographic region.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.17
	Confidence Interval	(2-Sided) 95%; 0.11 to 0.25
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio was estimated by Cox regression model.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab, Venetoclax + Rituximab
	Comments	Unstratified Analysis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.17
	Confidence Interval	(2-Sided) 95%; 0.12 to 0.26
	Parameter Dispersion	Type: Value:
	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.
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.

Arm/Group Title	Bendamustine + Rituximab	Venetoclax + Rituximab
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.
Measure Participants	195	194
Number [percentage of participants]	54.4 27.9%	18.0 9.3%

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.
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.

Arm/Group Title	Bendamustine + Rituximab	Venetoclax + Rituximab
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.
Measure Participants	195	194
Median (95% Confidence Interval) [months]	18.1	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab, Venetoclax + Rituximab
	Comments	Stratified Analysis; Stratification factors: 17p deletion, risk status, geographic region.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.19
	Confidence Interval	(2-Sided) 95%; 0.13 to 0.28
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio was estimated by Cox regression model.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab, Venetoclax + Rituximab
	Comments	Unstratified Analysis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.20
	Confidence Interval	(2-Sided) 95%; 0.14 to 0.30
	Parameter Dispersion	Type: Value:
	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.
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.
Measure Participants	46	46
Number [percentage of participants]	58.7 30.1%	15.2 7.8%

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 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.
Measure Participants	46	46
Median (95% Confidence Interval) [months]	15.4	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab, Venetoclax + Rituximab
	Comments	Stratified Analysis; Stratification factor: geographic region.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.13
	Confidence Interval	(2-Sided) 95%; 0.05 to 0.31
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio was estimated by Cox regression model.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab, Venetoclax + Rituximab
	Comments	Unstratified Analysis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.13
	Confidence Interval	(2-Sided) 95%; 0.05 to 0.29
	Parameter Dispersion	Type: Value:
	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.
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.
Measure Participants	46	46
Number [percentage of participants]	47.8 24.5%	19.6 10.1%

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.
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.
Measure Participants	46	46
Median (95% Confidence Interval) [months]	16.1	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab, Venetoclax + Rituximab
	Comments	Stratified Analysis; Stratification factor: geographic region.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.21
	Confidence Interval	(2-Sided) 95%; 0.09 to 0.49
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio was estimated by Cox regression model.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab, Venetoclax + Rituximab
	Comments	Unstratified Analysis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.21
	Confidence Interval	(2-Sided) 95%; 0.09 to 0.46
	Parameter Dispersion	Type: Value:
	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 the investigator according to the iwCLL guidelines and was confirmed by repeat assessment >/=4 weeks after initial documentation. CR: peripheral blood lymphocytes <4000/mcL; absence of any new lesion, nodal disease, lymphadenopathy, hepatomegaly, splenomegaly, and constitutional symptoms; neutrophils >1500/mcL, platelets >100000/mcL, hemoglobin >11.0 g/dL without need for transfusion or exogenous growth factors; normocellular bone marrow with <30% lymphocytes; no lymphoid nodules. CRi: fulfilling all CR criteria but persistent cytopenia. PR: >/=50% reduction in two of the following: peripheral blood lymphocytes, lymphadenopathy, spleen and/or liver enlargement; and one of the following: neutrophils >1500/mcL, platelets >100000/mcL, hemoglobin >11.0 g/dL or >/=50% improvement without need for transfusion or exogenous growth factors. nPR: fulfilling all CR criteria but presence of lymphoid nodules. The 95% CI was computed using Pearson-Clopper method.
Time Frame	Baseline up to last follow-up visit (FUV) (maximum up to data cut-off date, overall approximately 3 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Participants without post-baseline response assessment were considered as non-responders.

Arm/Group Title	Bendamustine + Rituximab	Venetoclax + Rituximab
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.
Measure Participants	195	194
Number (95% Confidence Interval) [percentage of participants]	67.7 34.7%	93.3 48.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab, Venetoclax + Rituximab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	25.61
	Confidence Interval	(2-Sided) 95%; 17.88 to 33.33
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% CI was computed using Anderson-Hauck method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab, Venetoclax + Rituximab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	7.81
	Confidence Interval	(2-Sided) 95%; 3.97 to 15.37
	Parameter Dispersion	Type: Value:
	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 the IRC according to the iwCLL guidelines and was confirmed by repeat assessment >/=4 weeks after initial documentation. CR: peripheral blood lymphocytes <4000/mcL; absence of any new lesion, nodal disease, lymphadenopathy, hepatomegaly, splenomegaly, and constitutional symptoms; neutrophils >1500/mcL, platelets >100000/mcL, hemoglobin >11.0 g/dL without need for transfusion or exogenous growth factors; normocellular bone marrow with <30% lymphocytes; no lymphoid nodules. CRi: fulfilling all CR criteria but persistent cytopenia. PR: >/=50% reduction in two of the following: peripheral blood lymphocytes, lymphadenopathy, spleen and/or liver enlargement; and one of the following: neutrophils >1500/mcL, platelets >100000/mcL, hemoglobin >11.0 g/dL or >/=50% improvement without need for transfusion or exogenous growth factors. nPR: fulfilling all CR criteria but presence of lymphoid nodules. The 95% CI was computed using Pearson-Clopper method.
Time Frame	Baseline up to last FUV (maximum up to data cut-off date, overall approximately 3 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Participants without post-baseline response assessment were considered as non-responders.

Arm/Group Title	Bendamustine + Rituximab	Venetoclax + Rituximab
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.
Measure Participants	195	194
Number (95% Confidence Interval) [percentage of participants]	72.3 37.1%	92.3 47.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab, Venetoclax + Rituximab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	19.96
	Confidence Interval	(2-Sided) 95%; 12.36 to 27.56
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% CI was computed using Anderson-Hauck method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab, Venetoclax + Rituximab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.79
	Confidence Interval	(2-Sided) 95%; 2.56 to 8.99
	Parameter Dispersion	Type: Value:
	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 the investigator according to the iwCLL guidelines and was confirmed by repeat assessment >/=4 weeks after initial documentation. CR: peripheral blood lymphocytes <4000/mcL; absence of any new lesion, nodal disease, lymphadenopathy, hepatomegaly, splenomegaly, and constitutional symptoms; neutrophils >1500/mcL, platelets >100000/mcL, hemoglobin >11.0 g/dL without need for transfusion or exogenous growth factors; normocellular bone marrow with <30% lymphocytes; no lymphoid nodules. CRi: fulfilling all CR criteria but persistent cytopenia. PR: >/=50% reduction in two of the following: peripheral blood lymphocytes, lymphadenopathy, spleen and/or liver enlargement; and one of the following: neutrophils >1500/mcL, platelets >100000/mcL, hemoglobin >11.0 g/dL or >/=50% improvement without need for transfusion or exogenous growth factors. nPR: fulfilling all CR criteria but presence of lymphoid nodules. The 95% CI was computed using Pearson-Clopper method.
Time Frame	End of combination treatment response (EoCTR) visit (8 to 12 weeks after Cycle [C] 6 Day [1]); Cycle length = 28 days

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Participants without post-baseline response assessment were considered as non-responders.

Arm/Group Title	Bendamustine + Rituximab	Venetoclax + Rituximab
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.
Measure Participants	195	194
Number (95% Confidence Interval) [percentage of participants]	62.6 32.1%	88.1 45.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab, Venetoclax + Rituximab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	25.58
	Confidence Interval	(2-Sided) 95%; 17.13 to 34.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% CI was computed using Anderson-Hauck method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab, Venetoclax + Rituximab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.75
	Confidence Interval	(2-Sided) 95%; 2.76 to 8.16
	Parameter Dispersion	Type: Value:
	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

Analysis was performed on ITT population. Participants without post-baseline response assessment were considered as non-responders.

Arm/Group Title	Bendamustine + Rituximab	Venetoclax + Rituximab
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.
Measure Participants	195	194
Number (95% Confidence Interval) [percentage of participants]	62.6 32.1%	87.1 44.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab, Venetoclax + Rituximab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	24.55
	Confidence Interval	(2-Sided) 95%; 16.00 to 33.10
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% CI was computed using Anderson-Hauck method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab, Venetoclax + Rituximab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.59
	Confidence Interval	(2-Sided) 95%; 2.68 to 7.85
	Parameter Dispersion	Type: Value:
	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.
Time Frame	Baseline up to last FUV (maximum up to Data Cut-off date, overall approximately 3 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Bendamustine + Rituximab	Venetoclax + Rituximab
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.
Measure Participants	195	194
Number [percentage of participants]	13.8 7.1%	7.7 4%

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 last FUV (maximum up to Data Cut-off date, overall approximately 3 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Bendamustine + Rituximab	Venetoclax + Rituximab
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.
Measure Participants	195	194
Median (95% Confidence Interval) [months]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab, Venetoclax + Rituximab
	Comments
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis; Stratification factors: 17p deletion, risk status, geographic region.
Statistical Test of Hypothesis	p-Value	0.0186
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.48
	Confidence Interval	(2-Sided) 95%; 0.25 to 0.90
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio was estimated by Cox regression model.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab, Venetoclax + Rituximab
	Comments	Unstratified Analysis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0190
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.48
	Confidence Interval	(2-Sided) 95%; 0.25 to 0.90
	Parameter Dispersion	Type: Value:
	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.
Time Frame	Baseline up to PD/relapse, start of a new anti-CLL therapy, or death from any cause, whichever occurred first (maximum up to Data Cut-off date, overall approximately 3 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Bendamustine + Rituximab	Venetoclax + Rituximab
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.
Measure Participants	195	194
Number [percentage of participants]	60.5 31%	17.0 8.8%

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 (maximum up to Data Cut-off date, overall approximately 3 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Bendamustine + Rituximab	Venetoclax + Rituximab
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.
Measure Participants	195	194
Median (95% Confidence Interval) [months]	16.4	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab, Venetoclax + Rituximab
	Comments	Stratified Analysis; Stratification factors: 17p deletion, risk status, geographic region.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.17
	Confidence Interval	(2-Sided) 95%; 0.11 to 0.25
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio was estimated by Cox regression model.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab, Venetoclax + Rituximab
	Comments	Unstratified Analysis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.18
	Confidence Interval	(2-Sided) 95%; 0.12 to 0.26
	Parameter Dispersion	Type: Value:
	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.
Time Frame	From time of achieving best overall response until PD or death from any cause, whichever occurred first (up to approximately 3 years)

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	Venetoclax + Rituximab
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.
Measure Participants	132	181
Number [percentage of participants]	53.8 27.6%	11.0 5.7%

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 3 years)

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	Venetoclax + Rituximab
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.
Measure Participants	132	181
Median (95% Confidence Interval) [months]	19.4	NA

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.
Time Frame	Baseline up to start of new ani-CLL therapy or death, whichever occurred first (up to approximately 3 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Bendamustine + Rituximab	Venetoclax + Rituximab
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.
Measure Participants	195	194
Number [percentage of participants]	42.6 21.8%	11.9 6.1%

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 3 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Bendamustine + Rituximab	Venetoclax + Rituximab
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.
Measure Participants	195	194
Median (95% Confidence Interval) [months]	26.4	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab, Venetoclax + Rituximab
	Comments	Stratified Analysis; Stratification factors: 17p deletion, risk status, geographic region.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.19
	Confidence Interval	(2-Sided) 95%; 0.12 to 0.31
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio was estimated by Cox regression model.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab, Venetoclax + Rituximab
	Comments	Unstratified Analysis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.19
	Confidence Interval	(2-Sided) 95%; 0.12 to 0.31
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio was estimated by Cox regression model.

21. Secondary Outcome

Title	Percentage of Participants With Minimal Residual Disease (MRD) Negativity at the EoCTR Visit
Description	MRD-negativity was defined as the presence of <1 malignant B-cell per 10000 normal B-cells in a sample of at least 200000 B-cells, as assessed by the allele specific oligonucleotide polymerase chain reaction (ASO-PCR) and/or flow cytometry technique. Percentage of participants with MRD-negativity at the EoCTR visit was reported. The 95% CI was computed using Pearson-Clopper method.
Time Frame	EoCTR visit (8 to 12 weeks after C6D1); Cycle length = 28 days

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Bendamustine + Rituximab	Venetoclax + Rituximab
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.
Measure Participants	195	194
Number (95% Confidence Interval) [percentage of participants]	13.3 6.8%	62.4 32.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab, Venetoclax + Rituximab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in MRD Negativity Rates
	Estimated Value	49.04
	Confidence Interval	(2-Sided) 95%; 40.44 to 57.64
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% CI was computed using Anderson-Hauck method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bendamustine + Rituximab, Venetoclax + Rituximab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	10.77
	Confidence Interval	(2-Sided) 95%; 6.50 to 17.85
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR was estimated using logistic regression model. The 95% CI was computed using Wald test.

22. Secondary Outcome

Title	Plasma Venetoclax Concentrations
Time Frame	Pre-dose (0 hour, anytime before venetoclax administeration) and 4 hours post-dose on D1 of Cycles 1 and 4; Cycle length = 28 days

Outcome Measure Data

Analysis Population Description

Analysis was performed on Pharmacokinetic (PK)-Evaluable population, which included all participants in the 'Venetoclax + Rituximab' arm and who received at least one dose of venetoclax with at least one post-dose PK concentration result available. Here 'Number Analyzed' signifies the number of participants evaluable at specified time point.

Arm/Group Title	Venetoclax + Rituximab
Arm/Group Description	Participants were initially placed on a venetoclax ramp-up period of 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
Measure Participants	184
C1D1, Pre-dose	0.626 (0.540)
C1D1, 4 hours Post-Dose	1.34 (0.881)
C4D1, Pre-dose	0.681 (0.745)
C4D1, 4 hours Post-Dose	1.34 (0.905)

23. Secondary Outcome

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

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

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

Analysis was performed on patient reported outcome (PRO)-evaluable population, which included all participants with baseline and at least one post-baseline PRO assessment. Here, 'Overall Number of Participants Analyzed' = participants evaluable for this outcome measure and 'Number Analyzed' = participants evaluable at specified time point.

Arm/Group Title	Bendamustine + Rituximab	Venetoclax + Rituximab
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.
Measure Participants	117	42
Baseline; Mean core symptom severity	1.76 (1.55)	1.55 (1.31)
Change at C1D1; Mean core symptom severity	0.00 (0.00)	-0.08 (0.98)
Change at C1D8; Mean core symptom severity	0.26 (1.34)	-0.30 (0.84)
Change at C1D15; Mean core symptom severity	0.00 (1.31)	-0.27 (0.93)
Change at C2D1; Mean core symptom severity	-0.23 (1.30)	-0.33 (0.91)
Change at C2D8; Mean core symptom severity	0.17 (1.59)	-0.45 (0.91)
Change at C2D15; Mean core symptom severity	-0.13 (1.53)	-0.53 (0.90)
Change at C3D1; Mean core symptom severity	-0.26 (1.60)	-0.40 (1.13)
Change at C3D8; Mean core symptom severity	-0.13 (1.63)	-0.66 (1.20)
Change at C3D15; Mean core symptom severity	-0.42 (1.52)	-0.53 (1.05)
Baseline; Mean module symptom severity	1.60 (1.46)	1.57 (1.11)
Change at C1D1; Mean module symptom severity	0.00 (0.00)	-0.19 (0.96)
Change at C1D8; Mean module symptom severity	-0.22 (1.40)	-0.53 (0.96)
Change at C1D15; Mean module symptom severity	-0.43 (1.51)	-0.73 (1.13)
Change at C2D1; Mean module symptom severity	-0.49 (1.46)	-0.65 (0.92)
Change at C2D8; Mean module symptom severity	-0.46 (1.63)	-0.77 (0.87)
Change at C2D15; Mean module symptom severity	-0.69 (1.47)	-0.94 (0.93)
Change at C3D1; Mean module symptom severity	-0.65 (1.48)	-0.81 (0.97)
Change at C3D8; Mean module symptom severity	-0.51 (1.58)	-0.83 (0.97)
Change at C3D15; Mean module symptom severity	-0.83 (1.51)	-0.92 (0.97)
Baseline; Mean interference	1.81 (2.05)	1.90 (2.25)
Change at C1D1; Mean interference	0.00 (0.00)	-0.13 (1.49)
Change at C1D8; Mean interference	0.45 (1.78)	-0.29 (2.14)
Change at C1D15; Mean interference	0.36 (1.85)	0.01 (2.04)
Change at C2D1; Mean interference	0.01 (1.73)	-0.34 (1.78)
Change at C2D8; Mean interference	0.58 (2.20)	-0.58 (1.81)
Change at C2D15; Mean interference	0.06 (1.84)	-0.64 (1.59)
Change at C3D1; Mean interference	-0.02 (2.02)	-0.73 (2.06)
Change at C3D8; Mean interference	0.15 (1.91)	-0.82 (2.09)
Change at C3D15; Mean interference	-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	The EORTC QLQ-C30 is a validated self-report measure consisting of 30 questions incorporated into five functional scales (Physical, Role, Cognitive, Emotional, and Social scales), three symptom scales (fatigue, pain, nausea, and vomiting scales), a global health status/global QoL scale, and single items (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea). Most questions used 4-point scale (1='Not at all' to 4='Very much'), while 2 questions used 7-point scale (1='very poor' to 7='Excellent'). Functional scales score and global health status/global QoL scale score are reported. Scores were averaged, transformed to 0-100 scale; where higher score for functional scales = poor level of functioning and higher score for global health status/global QoL = better HRQoL.
Time Frame	Baseline, D1 of Cycles 1, 2, 3, 4, 5, 6, STC/EW visit (up to C6D28), EoCTR visit (8 to 12 weeks after C6D1), and FUVs (every 12 weeks after EoCTR up to 3 years); Cycle length = 28 days

Outcome Measure Data

Analysis Population Description

Analysis was performed on PRO-evaluable population. Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'Number Analyzed' signifies the number of participants evaluable at specified time point.

Arm/Group Title	Bendamustine + Rituximab	Venetoclax + Rituximab
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.
Measure Participants	177	69
Baseline; Physical functioning	82.59 (17.46)	83.77 (15.27)
Change at C1D1; Physical functioning	0.0 (0.0)	1.39 (12.90)
Change at C2D1; Physical functioning	0.31 (15.81)	2.99 (12.83)
Change at C3D1; Physical functioning	0.22 (16.43)	1.46 (14.76)
Change at C4D1; Physical functioning	2.11 (14.95)	5.54 (14.17)
Change at C5D1; Physical functioning	2.44 (18.19)	4.62 (15.27)
Change at C6D1; Physical functioning	2.25 (16.82)	4.51 (16.59)
Change at STC/EW; Physical functioning	1.68 (18.76)	4.53 (16.04)
Change at EoCTR; Physical functioning	2.92 (18.03)	4.34 (16.12)
Change at FUV1; Physical functioning	2.27 (18.86)	3.81 (16.27)
Change at FUV2; Physical functioning	2.40 (19.21)	2.75 (17.17)
Change at FUV3; Physical functioning	2.54 (17.83)	3.44 (17.31)
Change at FUV4; Physical functioning	4.74 (20.14)	0.85 (21.06)
Change at FUV5; Physical functioning	1.90 (17.68)	-1.75 (19.35)
Change at FUV6; Physical functioning	-1.41 (15.34)	1.33 (5.58)
Change at FUV7; Physical functioning	-3.08 (11.74)	0.00
Change at FUV8; Physical functioning	-9.33 (23.38)	0.00
Change at FUV9; Physical functioning	-10.00 (33.0)
Baseline; Role functioning	78.25 (25.67)	83.82 (21.00)
Change at C1D1; Role functioning	0.0 (0.0)	-1.74 (23.23)
Change at C2D1; Role functioning	-1.26 (27.45)	2.49 (23.07)
Change at C3D1; Role functioning	-0.10 (29.64)	1.82 (26.08)
Change at C4D1; Role functioning	0.87 (29.01)	5.13 (22.03)
Change at C5D1; Role functioning	0.45 (30.75)	4.36 (23.44)
Change at C6D1; Role functioning	0.70 (29.92)	1.79 (25.71)
Change at STC/EW; Role functioning	-0.41 (32.91)	2.60 (25.58)
Change at EoCTR; Role functioning	3.26 (29.95)	2.12 (26.69)
Change at FUV1; Role functioning	2.93 (32.31)	2.65 (27.47)
Change at FUV2; Role functioning	3.07 (32.63)	-1.85 (31.84)
Change at FUV3; Role functioning	5.26 (31.16)	1.88 (28.17)
Change at FUV4; Role functioning	5.41 (33.16)	-0.35 (30.39)
Change at FUV5; Role functioning	2.34 (29.79)	1.75 (34.20)
Change at FUV6; Role functioning	-4.04 (27.01)	-13.33 (32.06)
Change at FUV7; Role functioning	2.56 (29.54)	-16.67
Change at FUV8; Role functioning	0.00 (23.57)	16.67
Change at FUV9; Role functioning	-16.67 (23.57)
Baseline; Emotional functioning	78.98 (22.47)	82.13 (15.80)
Change at C1D1; Emotional functioning	0.0 (0.0)	4.35 (15.17)
Change at C2D1; Emotional functioning	2.24 (20.07)	5.60 (14.68)
Change at C3D1; Emotional functioning	2.99 (20.06)	5.34 (19.09)
Change at C4D1; Emotional functioning	2.61 (18.35)	4.19 (15.45)
Change at C5D1; Emotional functioning	1.14 (18.79)	3.97 (17.37)
Change at C6D1; Emotional functioning	2.06 (18.74)	3.08 (17.96)
Change at STC/EW; Emotional functioning	2.43 (20.61)	5.34 (18.69)
Change at EoCTR; Emotional functioning	2.58 (19.45)	3.49 (17.83)
Change at FUV1; Emotional functioning	3.49 (20.91)	4.37 (18.50)
Change at FUV2; Emotional functioning	4.39 (20.33)	0.66 (21.02)
Change at FUV3; Emotional functioning	0.63 (19.97)	2.82 (17.66)
Change at FUV4; Emotional functioning	4.82 (19.73)	1.95 (18.41)
Change at FUV5; Emotional functioning	3.13 (17.95)	2.63 (20.61)
Change at FUV6; Emotional functioning	2.27 (21.78)	5.00 (17.28)
Change at FUV7; Emotional functioning	5.77 (17.48)	-8.33
Change at FUV8; Emotional functioning	3.33 (28.01)	0.00
Change at FUV9; Emotional functioning	-16.67 (11.79)
Baseline; Cognitive functioning	86.55 (16.78)	89.86 (14.91)
Change at C1D1; Cognitive functioning	0.0 (0.0)	-1.24 (14.01)
Change at C2D1; Cognitive functioning	-0.19 (15.34)	0.25 (14.06)
Change at C3D1; Cognitive functioning	-0.32 (16.34)	-1.56 (17.50)
Change at C4D1; Cognitive functioning	-1.54 (17.41)	-0.26 (17.05)
Change at C5D1; Cognitive functioning	-1.94 (18.10)	-0.26 (14.28)
Change at C6D1; Cognitive functioning	-2.68 (16.97)	-0.77 (15.98)
Change at STC/EW; Cognitive functioning	-2.19 (17.65)	1.04 (18.28)
Change at EoCTR; Cognitive functioning	-2.23 (18.11)	-0.27 (16.94)
Change at FUV1; Cognitive functioning	-2.02 (17.21)	-0.26 (15.98)
Change at FUV2; Cognitive functioning	1.32 (16.16)	-2.38 (18.17)
Change at FUV3; Cognitive functioning	-1.63 (14.84)	-2.96 (18.24)
Change at FUV4; Cognitive functioning	0.44 (17.63)	-1.77 (19.11)
Change at FUV5; Cognitive functioning	-1.49 (15.66)	-6.14 (21.67)
Change at FUV6; Cognitive functioning	-0.51 (14.72)	0.00 (0.00)
Change at FUV7; Cognitive functioning	-1.28 (14.37)	0.00
Change at FUV8; Cognitive functioning	0.00 (23.57)	0.00
Change at FUV9; Cognitive functioning	16.67 (23.57)
Baseline; Social functioning	82.48 (22.06)	85.51 (21.18)
Change at C1D1; Social functioning	0.0 (0.0)	-1.74 (19.92)
Change at C2D1; Social functioning	-2.44 (21.44)	0.25 (18.46)
Change at C3D1; Social functioning	-2.32 (22.61)	3.65 (25.45)
Change at C4D1; Social functioning	-0.55 (22.15)	4.62 (20.09)
Change at C5D1; Social functioning	-5.48 (26.49)	2.56 (20.46)
Change at C6D1; Social functioning	-5.13 (24.80)	3.85 (24.61)
Change at STC/EW; Social functioning	-4.06 (27.71)	1.04 (19.22)
Change at EoCTR; Social functioning	-0.47 (24.95)	1.88 (20.49)
Change at FUV1; Social functioning	-1.08 (26.09)	1.59 (24.27)
Change at FUV2; Social functioning	0.58 (24.68)	1.32 (27.97)
Change at FUV3; Social functioning	-0.91 (24.00)	1.88 (25.98)
Change at FUV4; Social functioning	1.97 (27.35)	1.06 (32.12)
Change at FUV5; Social functioning	1.79 (26.72)	0.00 (33.79)
Change at FUV6; Social functioning	1.52 (29.27)	10.00 (14.91)
Change at FUV7; Social functioning	-2.56 (23.42)	33.33
Change at FUV8; Social functioning	-10.00 (22.36)	33.33
Change at FUV9; Social functioning	-25.00 (35.36)
Baseline; Global health status/QoL	63.02 (21.45)	67.39 (22.17)
Change at C1D1; Global health status/QoL	0.0 (0.0)	6.34 (18.41)
Change at C2D1; Global health status/QoL	2.73 (21.69)	5.35 (20.14)
Change at C3D1; Global health status/QoL	2.34 (24.66)	2.21 (23.58)
Change at C4D1; Global health status/QoL	3.84 (22.26)	7.05 (21.05)
Change at C5D1; Global health status/QoL	7.36 (24.20)	7.18 (21.94)
Change at C6D1; Global health status/QoL	4.25 (25.00)	5.90 (25.16)
Change at STC/EW; Global health status/QoL	4.32 (26.20)	6.51 (23.22)
Change at EoCTR; Global health status/QoL	6.10 (23.65)	7.66 (24.11)
Change at FUV1; Global health status/QoL	5.91 (24.57)	7.01 (25.01)
Change at FUV2; Global health status/QoL	6.94 (24.81)	4.50 (26.51)
Change at FUV3; Global health status/QoL	4.80 (25.30)	6.32 (27.36)
Change at FUV4; Global health status/QoL	7.35 (26.77)	6.38 (27.60)
Change at FUV5; Global health status/QoL	4.46 (23.89)	4.39 (18.08)
Change at FUV6; Global health status/QoL	1.01 (24.00)	5.00 (7.45)
Change at FUV7; Global health status/QoL	8.33 (25.69)	16.67
Change at FUV8; Global health status/QoL	6.67 (16.03)	8.33
Change at FUV9; Global health status/QoL	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

Analysis was performed on PRO-evaluable population. Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'Number Analyzed' signifies the number of participants evaluable at specified time point.

Arm/Group Title	Bendamustine + Rituximab	Venetoclax + Rituximab
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.
Measure Participants	175	69
Baseline; TRSE	14.29 (13.95)	9.42 (8.80)
Change at C1D1; TRSE	0.0 (0.0)	0.12 (10.10)
Change at C2D1; TRSE	1.62 (13.82)	0.62 (12.76)
Change at C3D1; TRSE	-0.26 (13.76)	1.98 (14.72)
Change at C4D1; TRSE	-0.49 (13.97)	0.52 (11.87)
Change at C5D1; TRSE	-0.51 (14.57)	0.64 (10.02)
Change at C6D1; TRSE	0.46 (15.51)	-0.13 (10.04)
Change at STC/EW; TRSE	0.81 (18.11)	0.13 (10.76)
Change at EoCTR; TRSE	-0.88 (16.06)	0.26 (12.61)
Change at FUV1; TRSE	-1.20 (14.87)	1.19 (12.24)
Change at FUV2; TRSE	-1.70 (15.28)	2.65 (14.03)
Change at FUV3; TRSE	-2.08 (12.64)	-0.13 (13.70)
Change at FUV4; TRSE	-1.97 (12.76)	2.84 (15.18)
Change at FUV5; TRSE	-2.68 (11.02)	1.32 (10.49)
Change at FUV6; TRSE	-1.01 (12.10)	-1.67 (3.73)
Change at FUV7; TRSE	2.56 (22.67)	-8.33
Change at FUV8; TRSE	1.67 (13.69)	0.00
Change at FUV9; TRSE	8.33 (11.79)
Baseline; DRS	19.57 (16.81)	16.95 (17.37)
Change at C1D1; DRS	0.0 (0.0)	-2.74 (16.18)
Change at C2D1; DRS	-3.33 (16.05)	-4.77 (16.84)
Change at C3D1; DRS	-4.77 (16.49)	-3.35 (17.48)
Change at C4D1; DRS	-6.03 (16.51)	-5.12 (17.72)
Change at C5D1; DRS	-5.90 (16.73)	-4.79 (17.50)
Change at C6D1; DRS	-6.40 (17.26)	-5.30 (16.72)
Change at STC/EW; DRS	-5.80 (18.52)	-6.51 (18.45)
Change at EoCTR; DRS	-6.57 (17.21)	-5.86 (20.38)
Change at FUV1; DRS	-6.55 (15.73)	-5.82 (19.20)
Change at FUV2; DRS	-8.63 (14.39)	-3.57 (18.31)
Change at FUV3; DRS	-7.37 (14.88)	-3.76 (19.25)
Change at FUV4; DRS	-8.55 (18.56)	-2.66 (20.49)
Change at FUV5; DRS	-8.33 (16.13)	-2.19 (19.41)
Change at FUV6; DRS	-6.31 (16.01)	-3.33 (13.94)
Change at FUV7; DRS	-15.38 (20.08)	-8.33
Change at FUV8; DRS	-10.00 (16.03)	-8.33
Change at FUV9; DRS	-4.17 (5.89)
Baseline; Fatigue	28.76 (24.66)	21.74 (20.67)
Change at C1D1; Fatigue	0.0 (0.0)	-2.24 (20.29)
Change at C2D1; Fatigue	-2.55 (22.86)	-5.47 (21.40)
Change at C3D1; Fatigue	-2.83 (25.17)	-3.17 (23.73)
Change at C4D1; Fatigue	-3.18 (23.23)	-4.17 (22.02)
Change at C5D1; Fatigue	-2.38 (27.52)	-4.36 (20.89)
Change at C6D1; Fatigue	-2.66 (26.35)	-2.31 (21.42)
Change at STC/EW; Fatigue	-3.11 (28.64)	-4.69 (21.30)
Change at EoCTR; Fatigue	-6.69 (26.78)	-3.97 (24.27)
Change at FUV1; Fatigue	-6.37 (26.61)	-4.23 (22.99)
Change at FUV2; Fatigue	-6.64 (24.55)	-1.85 (24.70)
Change at FUV3; Fatigue	-5.79 (23.29)	-2.42 (23.73)
Change at FUV4; Fatigue	-9.65 (26.84)	-0.35 (25.18)
Change at FUV5; Fatigue	-6.55 (25.56)	3.51 (23.95)
Change at FUV6; Fatigue	-5.05 (24.82)	3.33 (24.72)
Change at FUV7; Fatigue	-10.26 (30.08)	-33.33
Change at FUV8; Fatigue	-6.67 (19.00)	0.00
Change at FUV9; Fatigue	-8.33 (11.79)
Baseline; Infection	15.92 (17.63)	14.01 (18.99)
Change at C1D1; Infection	0.0 (0.0)	-2.24 (20.03)
Change at C2D1; Infection	-0.02 (19.98)	-3.61 (21.72)
Change at C3D1; Infection	-1.66 (19.21)	-1.32 (20.48)
Change at C4D1; Infection	-1.44 (22.07)	-3.13 (21.28)
Change at C5D1; Infection	-1.91 (24.00)	-2.56 (23.47)
Change at C6D1; Infection	-1.09 (20.66)	-2.95 (20.54)
Change at STC/EW; Infection	-0.12 (23.28)	-1.69 (23.34)
Change at EoCTR; Infection	-0.55 (21.73)	-3.44 (25.78)
Change at FUV1; Infection	1.08 (18.77)	-2.65 (26.51)
Change at FUV2; Infection	0.05 (23.29)	-0.53 (25.74)
Change at FUV3; Infection	-1.90 (16.97)	-0.54 (26.48)
Change at FUV4; Infection	-4.24 (16.71)	0.53 (25.56)
Change at FUV5; Infection	-4.51 (22.66)	7.46 (27.20)
Change at FUV6; Infection	-1.60 (18.90)	8.33 (15.59)
Change at FUV7; Infection	-0.43 (21.84)	-16.67
Change at FUV8; Infection	8.89 (23.36)	-25.00
Change at FUV9; Infection	-2.78 (3.93)

27. Post-Hoc Outcome

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

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Baseline up to Follow-up (maximum up to Data Cut-off date, overall approximately 3 years)
Adverse Event Reporting Description	Analysis was performed on safety evaluable (SE) population, which included all randomized participants who received at least one dose of study treatment (venetoclax, rituximab, or bendamustine), with participants grouped according to the actual treatment received.
Arm/Group Title	Bendamustine + Rituximab		Venetoclax + Rituximab
Arm/Group Description	Participants received bendamustine at a dose of 70 mg/m^2 via IV infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.		Participants were initially placed on a venetoclax ramp-up period of 5 weeks, and received an initial dose of 20 mg via tablet orally QD for initial 1 to 7 days, then venetoclax dose was incremented weekly up to a maximum dose of 400 mg via tablet orally QD. Participants continued receiving venetoclax at a dose of 400 mg via tablet orally QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to PD or 2 years, whichever occurred first, as directed by the investigator, in combination with rituximab at a dose of 375 mg/m^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m^2 on Day 1 of Cycles 2-6.
All Cause Mortality
	Bendamustine + Rituximab		Venetoclax + Rituximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	27/188 (14.4%)		15/194 (7.7%)
Serious Adverse Events
	Bendamustine + Rituximab		Venetoclax + Rituximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	81/188 (43.1%)		90/194 (46.4%)
Blood and lymphatic system disorders
Anaemia	5/188 (2.7%)		3/194 (1.5%)
Autoimmune haemolytic anaemia	3/188 (1.6%)		3/194 (1.5%)
Disseminated intravascular coagulation	0/188 (0%)		1/194 (0.5%)
Febrile neutropenia	16/188 (8.5%)		7/194 (3.6%)
Immune thrombocytopenic purpura	0/188 (0%)		1/194 (0.5%)
Leukocytosis	1/188 (0.5%)		0/194 (0%)
Neutropenia	3/188 (1.6%)		3/194 (1.5%)
Pancytopenia	0/188 (0%)		1/194 (0.5%)
Thrombocytopenia	2/188 (1.1%)		2/194 (1%)
Cardiac disorders
Acute myocardial infarction	1/188 (0.5%)		0/194 (0%)
Angina pectoris	0/188 (0%)		1/194 (0.5%)
Atrial fibrillation	1/188 (0.5%)		0/194 (0%)
Cardiac failure	0/188 (0%)		1/194 (0.5%)
Coronary artery disease	1/188 (0.5%)		0/194 (0%)
Myocardial infarction	0/188 (0%)		2/194 (1%)
Ventricular tachycardia	0/188 (0%)		1/194 (0.5%)
Ear and labyrinth disorders
Deafness	0/188 (0%)		1/194 (0.5%)
Vertigo	0/188 (0%)		1/194 (0.5%)
Eye disorders
Eye haemorrhage	0/188 (0%)		1/194 (0.5%)
Gastrointestinal disorders
Abdominal pain	0/188 (0%)		1/194 (0.5%)
Anal fistula	1/188 (0.5%)		0/194 (0%)
Ascites	0/188 (0%)		1/194 (0.5%)
Colitis	1/188 (0.5%)		0/194 (0%)
Crohn's disease	0/188 (0%)		1/194 (0.5%)
Diarrhoea	0/188 (0%)		2/194 (1%)
Dyspepsia	0/188 (0%)		1/194 (0.5%)
Gastrointestinal haemorrhage	0/188 (0%)		1/194 (0.5%)
Nausea	1/188 (0.5%)		0/194 (0%)
Oesophageal obstruction	0/188 (0%)		1/194 (0.5%)
Small intestinal obstruction	0/188 (0%)		1/194 (0.5%)
Vomiting	1/188 (0.5%)		1/194 (0.5%)
General disorders
Asthenia	1/188 (0.5%)		0/194 (0%)
Hyperpyrexia	1/188 (0.5%)		1/194 (0.5%)
Malaise	1/188 (0.5%)		0/194 (0%)
Pyrexia	13/188 (6.9%)		5/194 (2.6%)
Sudden cardiac death	0/188 (0%)		1/194 (0.5%)
Sudden death	1/188 (0.5%)		0/194 (0%)
Unevaluable event	1/188 (0.5%)		0/194 (0%)
Hepatobiliary disorders
Bile duct obstruction	0/188 (0%)		1/194 (0.5%)
Infections and infestations
Abscess neck	1/188 (0.5%)		0/194 (0%)
Appendicitis	0/188 (0%)		2/194 (1%)
Atypical pneumonia	1/188 (0.5%)		0/194 (0%)
Bronchitis	2/188 (1.1%)		0/194 (0%)
Bronchopulmonary aspergillosis	1/188 (0.5%)		0/194 (0%)
Campylobacter gastroenteritis	0/188 (0%)		1/194 (0.5%)
Cellulitis	1/188 (0.5%)		0/194 (0%)
Clostridium difficile colitis	1/188 (0.5%)		0/194 (0%)
Cystitis	0/188 (0%)		1/194 (0.5%)
Diverticulitis	0/188 (0%)		1/194 (0.5%)
Erysipelas	0/188 (0%)		1/194 (0.5%)
Escherichia sepsis	1/188 (0.5%)		0/194 (0%)
Gastroenteritis rotavirus	0/188 (0%)		1/194 (0.5%)
Gastroenteritis viral	1/188 (0.5%)		0/194 (0%)
Haemophilus infection	0/188 (0%)		1/194 (0.5%)
Hepatitis B	1/188 (0.5%)		0/194 (0%)
Herpes simplex otitis externa	0/188 (0%)		1/194 (0.5%)
Herpes zoster	0/188 (0%)		1/194 (0.5%)
Influenza	2/188 (1.1%)		3/194 (1.5%)
Listeria sepsis	1/188 (0.5%)		0/194 (0%)
Localised infection	1/188 (0.5%)		0/194 (0%)
Lung infection	0/188 (0%)		3/194 (1.5%)
Meningitis	0/188 (0%)		1/194 (0.5%)
Moraxella infection	0/188 (0%)		1/194 (0.5%)
Neutropenic sepsis	1/188 (0.5%)		0/194 (0%)
Peritoneal tuberculosis	0/188 (0%)		1/194 (0.5%)
Pharyngitis	2/188 (1.1%)		0/194 (0%)
Pneumococcal bacteraemia	1/188 (0.5%)		0/194 (0%)
Pneumocystis jirovecii pneumonia	1/188 (0.5%)		0/194 (0%)
Pneumonia	15/188 (8%)		16/194 (8.2%)
Pneumonia influenzal	0/188 (0%)		1/194 (0.5%)
Pneumonia legionella	1/188 (0.5%)		0/194 (0%)
Pneumonia streptococcal	0/188 (0%)		1/194 (0.5%)
Respiratory tract infection	0/188 (0%)		2/194 (1%)
Respiratory tract infection fungal	0/188 (0%)		1/194 (0.5%)
Respiratory tract infection viral	0/188 (0%)		1/194 (0.5%)
Rhinovirus infection	0/188 (0%)		1/194 (0.5%)
Scedosporium infection	1/188 (0.5%)		0/194 (0%)
Sepsis	4/188 (2.1%)		1/194 (0.5%)
Septic shock	1/188 (0.5%)		0/194 (0%)
Sinusitis	1/188 (0.5%)		2/194 (1%)
Staphylococcal infection	1/188 (0.5%)		0/194 (0%)
Tooth abscess	0/188 (0%)		1/194 (0.5%)
Upper respiratory tract infection	2/188 (1.1%)		3/194 (1.5%)
Urinary tract infection	1/188 (0.5%)		1/194 (0.5%)
Urinary tract infection pseudomonal	0/188 (0%)		1/194 (0.5%)
Urosepsis	1/188 (0.5%)		0/194 (0%)
Varicella zoster virus infection	1/188 (0.5%)		0/194 (0%)
Viral infection	0/188 (0%)		1/194 (0.5%)
Viral upper respiratory tract infection	0/188 (0%)		1/194 (0.5%)
Lower respiratory tract infection	1/188 (0.5%)		0/194 (0%)
Parainfluenzae virus infection	1/188 (0.5%)		0/194 (0%)
Injury, poisoning and procedural complications
Humerus fracture	0/188 (0%)		1/194 (0.5%)
Infusion related reaction	6/188 (3.2%)		1/194 (0.5%)
Tendon rupture	1/188 (0.5%)		0/194 (0%)
Investigations
Body temperature increased	1/188 (0.5%)		0/194 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/188 (0%)		1/194 (0.5%)
Dehydration	0/188 (0%)		2/194 (1%)
Diabetes mellitus	0/188 (0%)		1/194 (0.5%)
Fluid overload	0/188 (0%)		1/194 (0.5%)
Hyperkalaemia	0/188 (0%)		2/194 (1%)
Hyperphosphataemia	0/188 (0%)		2/194 (1%)
Tumour lysis syndrome	1/188 (0.5%)		4/194 (2.1%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	1/188 (0.5%)		0/194 (0%)
Musculoskeletal chest pain	1/188 (0.5%)		0/194 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	1/188 (0.5%)		0/194 (0%)
Adenocarcinoma gastric	0/188 (0%)		1/194 (0.5%)
Adenocarcinoma of colon	1/188 (0.5%)		0/194 (0%)
Basal cell carcinoma	0/188 (0%)		1/194 (0.5%)
Colon cancer	0/188 (0%)		1/194 (0.5%)
Colorectal cancer	0/188 (0%)		2/194 (1%)
Lung neoplasm malignant	2/188 (1.1%)		0/194 (0%)
Lymphoma	1/188 (0.5%)		0/194 (0%)
Malignant melanoma	0/188 (0%)		1/194 (0.5%)
Medullary thyroid cancer	1/188 (0.5%)		0/194 (0%)
Metastatic malignant melanoma	0/188 (0%)		1/194 (0.5%)
Myelodysplastic syndrome	0/188 (0%)		2/194 (1%)
Pancreatic carcinoma	0/188 (0%)		1/194 (0.5%)
Prostate cancer	1/188 (0.5%)		0/194 (0%)
Prostatic adenoma	0/188 (0%)		1/194 (0.5%)
Skin cancer	0/188 (0%)		1/194 (0.5%)
Squamous cell carcinoma	1/188 (0.5%)		3/194 (1.5%)
Transitional cell carcinoma	1/188 (0.5%)		0/194 (0%)
Nervous system disorders
Dizziness	0/188 (0%)		1/194 (0.5%)
Haemorrhagic stroke	1/188 (0.5%)		0/194 (0%)
Lacunar infarction	0/188 (0%)		1/194 (0.5%)
Polyneuropathy	1/188 (0.5%)		0/194 (0%)
Status epilepticus	0/188 (0%)		1/194 (0.5%)
Syncope	1/188 (0.5%)		0/194 (0%)
Renal and urinary disorders
Acute kidney injury	1/188 (0.5%)		1/194 (0.5%)
Nephrolithiasis	0/188 (0%)		1/194 (0.5%)
Renal impairment	1/188 (0.5%)		0/194 (0%)
Reproductive system and breast disorders
Cervical dysplasia	0/188 (0%)		1/194 (0.5%)
Uterine haemorrhage	0/188 (0%)		1/194 (0.5%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/188 (0%)		1/194 (0.5%)
Bronchiectasis	0/188 (0%)		1/194 (0.5%)
Lung disorder	0/188 (0%)		1/194 (0.5%)
Pulmonary embolism	1/188 (0.5%)		1/194 (0.5%)
Skin and subcutaneous tissue disorders
Dermatitis allergic	1/188 (0.5%)		0/194 (0%)
Vascular disorders
Aortic stenosis	1/188 (0.5%)		0/194 (0%)
Deep vein thrombosis	1/188 (0.5%)		1/194 (0.5%)
Embolism	1/188 (0.5%)		0/194 (0%)
Hypotension	5/188 (2.7%)		0/194 (0%)
Other (Not Including Serious) Adverse Events
	Bendamustine + Rituximab		Venetoclax + Rituximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	176/188 (93.6%)		190/194 (97.9%)
Blood and lymphatic system disorders
Anaemia	40/188 (21.3%)		28/194 (14.4%)
Neutropenia	82/188 (43.6%)		118/194 (60.8%)
Thrombocytopenia	42/188 (22.3%)		24/194 (12.4%)
Gastrointestinal disorders
Abdominal pain	6/188 (3.2%)		13/194 (6.7%)
Constipation	39/188 (20.7%)		27/194 (13.9%)
Diarrhoea	31/188 (16.5%)		76/194 (39.2%)
Nausea	64/188 (34%)		41/194 (21.1%)
Vomiting	22/188 (11.7%)		15/194 (7.7%)
General disorders
Chills	16/188 (8.5%)		8/194 (4.1%)
Fatigue	39/188 (20.7%)		34/194 (17.5%)
Oedema peripheral	7/188 (3.7%)		11/194 (5.7%)
Pyrexia	33/188 (17.6%)		27/194 (13.9%)
Infections and infestations
Bronchitis	13/188 (6.9%)		20/194 (10.3%)
Conjunctivitis	5/188 (2.7%)		10/194 (5.2%)
Lower respiratory tract infection	4/188 (2.1%)		11/194 (5.7%)
Nasopharyngitis	10/188 (5.3%)		22/194 (11.3%)
Oral herpes	12/188 (6.4%)		8/194 (4.1%)
Pharyngitis	1/188 (0.5%)		13/194 (6.7%)
Pneumonia	11/188 (5.9%)		5/194 (2.6%)
Sinusitis	5/188 (2.7%)		17/194 (8.8%)
Upper respiratory tract infection	28/188 (14.9%)		41/194 (21.1%)
Urinary tract infection	7/188 (3.7%)		11/194 (5.7%)
Injury, poisoning and procedural complications
Infusion related reaction	40/188 (21.3%)		15/194 (7.7%)
Investigations
Alanine aminotransferase increased	10/188 (5.3%)		9/194 (4.6%)
Neutrophil count decreased	13/188 (6.9%)		11/194 (5.7%)
Metabolism and nutrition disorders
Decreased appetite	17/188 (9%)		8/194 (4.1%)
Hyperkalaemia	0/188 (0%)		11/194 (5.7%)
Hypokalaemia	7/188 (3.7%)		12/194 (6.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	10/188 (5.3%)		12/194 (6.2%)
Back pain	11/188 (5.9%)		15/194 (7.7%)
Muscle spasms	11/188 (5.9%)		4/194 (2.1%)
Nervous system disorders
Dizziness	10/188 (5.3%)		12/194 (6.2%)
Headache	19/188 (10.1%)		21/194 (10.8%)
Psychiatric disorders
Insomnia	12/188 (6.4%)		21/194 (10.8%)
Respiratory, thoracic and mediastinal disorders
Cough	31/188 (16.5%)		35/194 (18%)
Dyspnoea	14/188 (7.4%)		11/194 (5.7%)
Oropharyngeal pain	7/188 (3.7%)		10/194 (5.2%)
Productive cough	4/188 (2.1%)		12/194 (6.2%)
Skin and subcutaneous tissue disorders
Pruritus	8/188 (4.3%)		10/194 (5.2%)
Rash	24/188 (12.8%)		14/194 (7.2%)
Vascular disorders
Hypertension	7/188 (3.7%)		12/194 (6.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.