Trial Outcomes & Findings for A Study Evaluating the Safety and Efficacy of Venetoclax (GDC-0199) Plus Bendamustine + Rituximab (BR) in Comparison With BR or Venetoclax Plus Rituximab in Participants With Relapsed and Refractory Follicular Non-Hodgkin's Lymphoma (fNHL) (NCT NCT02187861)

Last Updated: 2019-06-05

Results Overview

CMR: a score 1 (no uptake above background), 2 (uptake less than or equal to \[\<=\] mediastinum), or 3 (uptake less than \[\<\] mediastinum but \<=liver) with or without a residual mass on PET 5-point scale (5-PS), for lymph nodes and extralymphatic sites with no new lesions and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. Assessment was performed by an IRC according to Lugano classification using PET scan. 95% confidence interval (CI) for percentage of responders was calculated using Clopper-Pearson method.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

163 participants

Primary outcome timeframe

6-8 weeks after Cycle 6 Day 1 (PRA) (Cycle length = 28 days)

Results posted on

2019-06-05

Participant Flow

Participant milestones

Participant milestones
Measure	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) Participants received venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in continued until first 9 participants completed the safety observation window of 28 days. After first 28 days of safety observation (Cycle 1), participants continued to receive venetoclax 600 mg orally once daily up to 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) Participants received venetoclax 800 mg orally once daily for 1 year along with rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, 10, and 12. Each cycle was of 28 days.	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) Participants received venetoclax 800 mg orally once daily continuously for 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Containing Cohort: Arm C (BR) Participants received rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.
Overall Study STARTED	9	52	51	51
Overall Study Treated	9	52	49	50
Overall Study COMPLETED	3	4	19	19
Overall Study NOT COMPLETED	6	48	32	32

Reasons for withdrawal

Reasons for withdrawal
Measure	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) Participants received venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in continued until first 9 participants completed the safety observation window of 28 days. After first 28 days of safety observation (Cycle 1), participants continued to receive venetoclax 600 mg orally once daily up to 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) Participants received venetoclax 800 mg orally once daily for 1 year along with rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, 10, and 12. Each cycle was of 28 days.	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) Participants received venetoclax 800 mg orally once daily continuously for 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Containing Cohort: Arm C (BR) Participants received rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.
Overall Study Adverse Event	2	1	2	1
Overall Study Death	0	3	1	2
Overall Study Physician Decision	0	1	0	3
Overall Study Progressive Disease	4	42	19	22
Overall Study Withdrawal by Subject	0	0	3	3
Overall Study Other	0	1	7	1

Baseline Characteristics

A Study Evaluating the Safety and Efficacy of Venetoclax (GDC-0199) Plus Bendamustine + Rituximab (BR) in Comparison With BR or Venetoclax Plus Rituximab in Participants With Relapsed and Refractory Follicular Non-Hodgkin's Lymphoma (fNHL)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) n=9 Participants Participants received venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in continued until first 9 participants completed the safety observation window of 28 days. After first 28 days of safety observation (Cycle 1), participants continued to receive venetoclax 600 mg orally once daily up to 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) n=52 Participants Participants received venetoclax 800 mg orally once daily for 1 year along with rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, 10, and 12. Each cycle was of 28 days.	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) n=51 Participants Participants received venetoclax 800 mg orally once daily continuously for 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Containing Cohort: Arm C (BR) n=51 Participants Participants received rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Total n=163 Participants Total of all reporting groups
Age, Continuous	57.9 years STANDARD_DEVIATION 12.7 • n=5 Participants	61.9 years STANDARD_DEVIATION 12.0 • n=7 Participants	64.9 years STANDARD_DEVIATION 9.8 • n=5 Participants	61.0 years STANDARD_DEVIATION 11.6 • n=4 Participants	62.3 years STANDARD_DEVIATION 11.3 • n=21 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	25 Participants n=7 Participants	16 Participants n=5 Participants	21 Participants n=4 Participants	67 Participants n=21 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	27 Participants n=7 Participants	35 Participants n=5 Participants	30 Participants n=4 Participants	96 Participants n=21 Participants

PRIMARY outcome

Timeframe: 6-8 weeks after Cycle 6 Day 1 (PRA) (Cycle length = 28 days)

Population: ITT population

Outcome measures

Outcome measures
Measure	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) n=9 Participants Participants received venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in continued until first 9 participants completed the safety observation window of 28 days. After first 28 days of safety observation (Cycle 1), participants continued to receive venetoclax 600 mg orally once daily up to 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) n=52 Participants Participants received venetoclax 800 mg orally once daily for 1 year along with rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, 10, and 12. Each cycle was of 28 days.	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) n=51 Participants Participants received venetoclax 800 mg orally once daily continuously for 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Containing Cohort: Arm C (BR) n=51 Participants Participants received rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.
Percentage of Participants With Complete Metabolic Response (CMR) According to Independent Review Committee (IRC) as Per Lugano Classification, Using Positron Emission Tomography (PET) Scan at Primary Response Assessment (PRA)	55.6 percentage of participants Interval 21.2 to 86.3	11.5 percentage of participants Interval 4.35 to 23.44	74.5 percentage of participants Interval 60.37 to 85.67	70.6 percentage of participants Interval 56.17 to 82.51

SECONDARY outcome

Timeframe: 4-10 weeks after Cycle 6 Day 1 (Cycle length = 28 days)

Population: ITT population

CMR: a score 1 (no uptake above background), 2 (uptake \<=mediastinum), or 3 (\<mediastinum but \<=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites with no new lesions and no evidence of FDG-avid disease in bone marrow. Assessment was performed by Investigator according to Lugano classification using PET scan. 95% CI for percentage of responders was calculated using Clopper-Pearson method.

Outcome measures

Outcome measures
Measure	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) n=9 Participants Participants received venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in continued until first 9 participants completed the safety observation window of 28 days. After first 28 days of safety observation (Cycle 1), participants continued to receive venetoclax 600 mg orally once daily up to 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) n=52 Participants Participants received venetoclax 800 mg orally once daily for 1 year along with rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, 10, and 12. Each cycle was of 28 days.	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) n=51 Participants Participants received venetoclax 800 mg orally once daily continuously for 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Containing Cohort: Arm C (BR) n=51 Participants Participants received rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.
Percentage of Participants With CMR According to Investigator as Per Lugano Classification, Using PET Scan at PRA	55.6 percentage of participants Interval 21.2 to 86.3	15.4 percentage of participants Interval 6.88 to 28.08	70.6 percentage of participants Interval 56.17 to 82.51	68.6 percentage of participants Interval 54.11 to 80.89

SECONDARY outcome

Timeframe: 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)

Population: ITT population

CMR: a score 1 (no uptake above background), 2 (uptake \<=mediastinum), or 3 (uptake \<mediastinum but \<=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites with no new lesions and no evidence of FDG-avid disease in bone marrow. Assessment was performed by an IRC according to Lugano classification using PET scan. 95% CI for percentage of responders was calculated using Clopper-Pearson method.

Outcome measures

Outcome measures
Measure	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) n=9 Participants Participants received venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in continued until first 9 participants completed the safety observation window of 28 days. After first 28 days of safety observation (Cycle 1), participants continued to receive venetoclax 600 mg orally once daily up to 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) n=52 Participants Participants received venetoclax 800 mg orally once daily for 1 year along with rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, 10, and 12. Each cycle was of 28 days.	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) n=51 Participants Participants received venetoclax 800 mg orally once daily continuously for 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Containing Cohort: Arm C (BR) n=51 Participants Participants received rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.
Percentage of Participants With CMR According to IRC as Per Lugano Classification, Using PET Scan at Year 1	55.6 percentage of participants Interval 21.2 to 86.3	21.2 percentage of participants Interval 11.06 to 34.7	41.2 percentage of participants Interval 27.58 to 55.83	39.2 percentage of participants Interval 25.84 to 53.89

SECONDARY outcome

Timeframe: 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)

Population: ITT population

Outcome measures

Outcome measures
Measure	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) n=9 Participants Participants received venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in continued until first 9 participants completed the safety observation window of 28 days. After first 28 days of safety observation (Cycle 1), participants continued to receive venetoclax 600 mg orally once daily up to 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) n=52 Participants Participants received venetoclax 800 mg orally once daily for 1 year along with rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, 10, and 12. Each cycle was of 28 days.	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) n=51 Participants Participants received venetoclax 800 mg orally once daily continuously for 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Containing Cohort: Arm C (BR) n=51 Participants Participants received rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.
Percentage of Participants With CMR According to Investigator as Per Lugano Classification, Using PET Scan at Year 1	55.6 percentage of participants Interval 21.2 to 86.3	17.3 percentage of participants Interval 8.23 to 30.33	39.2 percentage of participants Interval 25.84 to 53.89	47.1 percentage of participants Interval 32.93 to 61.54

SECONDARY outcome

Timeframe: 6-8 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)

Population: ITT population

CR: defined as reduction of longest transverse diameter of lesion (LDi) of target nodes/nodal masses to \<=1.5 centimeters (cm), and no extralymphatic sites of disease; absence of non-measured lesions and new lesions; reduction of enlarged organs to normal; and normal/immunohistochemistry (IHC)-negative bone marrow morphology. Assessment was performed by an IRC according to Lugano classification using CT scan. 95% CI for percentage of responders was calculated using Clopper-Pearson method.

Outcome measures

Outcome measures
Measure	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) n=9 Participants Participants received venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in continued until first 9 participants completed the safety observation window of 28 days. After first 28 days of safety observation (Cycle 1), participants continued to receive venetoclax 600 mg orally once daily up to 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) n=52 Participants Participants received venetoclax 800 mg orally once daily for 1 year along with rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, 10, and 12. Each cycle was of 28 days.	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) n=51 Participants Participants received venetoclax 800 mg orally once daily continuously for 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Containing Cohort: Arm C (BR) n=51 Participants Participants received rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.
Percentage of Participants With Complete Response (CR) According to IRC as Per Lugano Classification, Using Computed Tomography (CT) Scan 6-8 weeks after Cycle 6 Day 1	44.4 percentage of participants Interval 13.7 to 78.8	5.7 percentage of participants Interval 1.18 to 15.66	39.2 percentage of participants Interval 25.84 to 53.89	25.5 percentage of participants Interval 14.33 to 39.63
Percentage of Participants With Complete Response (CR) According to IRC as Per Lugano Classification, Using Computed Tomography (CT) Scan Year 1	55.6 percentage of participants Interval 21.2 to 86.3	13.2 percentage of participants Interval 5.48 to 25.34	27.5 percentage of participants Interval 15.89 to 41.74	23.5 percentage of participants Interval 12.79 to 37.49

SECONDARY outcome

Timeframe: 4-10 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)

Population: ITT population

CR: defined as reduction of LDi of target nodes/nodal masses to \<=1.5 cm, and no extralymphatic sites of disease; absence of non-measured lesions and new lesions; reduction of enlarged organs to normal; and normal/IHC-negative bone marrow morphology. Assessment was performed by Investigator according to Lugano classification using CT scan. 95% CI for percentage of responders was calculated using Clopper-Pearson method.

Outcome measures

Outcome measures
Measure	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) n=9 Participants Participants received venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in continued until first 9 participants completed the safety observation window of 28 days. After first 28 days of safety observation (Cycle 1), participants continued to receive venetoclax 600 mg orally once daily up to 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) n=52 Participants Participants received venetoclax 800 mg orally once daily for 1 year along with rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, 10, and 12. Each cycle was of 28 days.	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) n=51 Participants Participants received venetoclax 800 mg orally once daily continuously for 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Containing Cohort: Arm C (BR) n=51 Participants Participants received rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.
Percentage of Participants With CR According to Investigator as Per Lugano Classification, Using CT Scan Year 1	33.3 percentage of participants Interval 7.49 to 70.07	5.7 percentage of participants Interval 1.18 to 15.66	13.7 percentage of participants Interval 5.7 to 26.26	21.6 percentage of participants Interval 11.29 to 35.32
Percentage of Participants With CR According to Investigator as Per Lugano Classification, Using CT Scan 4-10 weeks after Cycle 6 Day 1	22.2 percentage of participants Interval 2.81 to 60.01	5.7 percentage of participants Interval 1.18 to 15.66	15.7 percentage of participants Interval 7.02 to 28.59	31.4 percentage of participants Interval 19.11 to 45.89

SECONDARY outcome

Timeframe: 6-8 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)

Population: ITT population

OR was defined as CMR or Partial Metabolic Response (PMR). CMR: a score 1 (no uptake above background), 2 (uptake \<=mediastinum), or 3 (\<mediastinum but \<=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites with no new lesions and no evidence of FDG-avid disease in bone marrow. PMR: a score 4 (uptake moderately greater than \[\>\] liver) or 5 (uptake markedly \>liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites with no new lesions and reduced residual uptake in bone marrow compared with baseline. Assessment was performed by an IRC according to Lugano classification using PET scan. 95% CI for percentage of responders was calculated using Clopper-Pearson method.

Outcome measures

Outcome measures
Measure	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) n=9 Participants Participants received venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in continued until first 9 participants completed the safety observation window of 28 days. After first 28 days of safety observation (Cycle 1), participants continued to receive venetoclax 600 mg orally once daily up to 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) n=52 Participants Participants received venetoclax 800 mg orally once daily for 1 year along with rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, 10, and 12. Each cycle was of 28 days.	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) n=51 Participants Participants received venetoclax 800 mg orally once daily continuously for 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Containing Cohort: Arm C (BR) n=51 Participants Participants received rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.
Percentage of Participants With Objective Response (OR) According to IRC as Per Lugano Classification, Using PET Scan 6-8 weeks after Cycle 6 Day 1	55.6 percentage of participants Interval 21.2 to 86.3	21.2 percentage of participants Interval 11.06 to 34.7	76.5 percentage of participants Interval 62.51 to 87.21	74.5 percentage of participants Interval 60.37 to 85.67
Percentage of Participants With Objective Response (OR) According to IRC as Per Lugano Classification, Using PET Scan Year 1	66.7 percentage of participants Interval 29.93 to 92.51	32.7 percentage of participants Interval 20.33 to 47.11	45.1 percentage of participants Interval 31.13 to 59.66	51.0 percentage of participants Interval 36.6 to 65.25

SECONDARY outcome

Timeframe: 4-10 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)

Population: ITT population

OR was defined as CMR or PMR. CMR: a score 1 (no uptake above background), 2 (uptake \<=mediastinum), or 3 (\<mediastinum but \<=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites with no new lesions and no evidence of FDG-avid disease in bone marrow. PMR: a score 4 (uptake moderately \>liver) or 5 (uptake markedly \>liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites with no new lesions and reduced residual uptake in bone marrow compared with baseline. Assessment was performed by Investigator according to Lugano classification using PET scan. 95% CI for percentage of responders was calculated using Clopper-Pearson method.

Outcome measures

Outcome measures
Measure	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) n=9 Participants Participants received venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in continued until first 9 participants completed the safety observation window of 28 days. After first 28 days of safety observation (Cycle 1), participants continued to receive venetoclax 600 mg orally once daily up to 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) n=52 Participants Participants received venetoclax 800 mg orally once daily for 1 year along with rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, 10, and 12. Each cycle was of 28 days.	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) n=51 Participants Participants received venetoclax 800 mg orally once daily continuously for 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Containing Cohort: Arm C (BR) n=51 Participants Participants received rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.
Percentage of Participants With OR According to Investigator as Per Lugano Classification, Using PET Scan 4-10 weeks after Cycle 6 Day 1	55.6 percentage of participants Interval 21.2 to 86.3	28.8 percentage of participants Interval 17.13 to 43.08	76.5 percentage of participants Interval 62.51 to 87.21	76.5 percentage of participants Interval 62.51 to 87.21
Percentage of Participants With OR According to Investigator as Per Lugano Classification, Using PET Scan Year 1	55.6 percentage of participants Interval 21.2 to 86.3	21.2 percentage of participants Interval 11.06 to 34.7	39.2 percentage of participants Interval 25.84 to 53.89	49.0 percentage of participants Interval 34.75 to 63.4

SECONDARY outcome

Timeframe: 6-8 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)

Population: ITT population

OR was defined as CR or Partial Response (PR). CR: reduction of LDi of target nodes/nodal masses to \<=1.5 cm, and no extralymphatic sites of disease; absence of non-measured lesions and new lesions; reduction of enlarged organs to normal; and normal/IHC-negative bone marrow morphology. PR: greater than or equal to (\>=) 50 percent (%) decrease in sum of the product of the perpendicular diameters (SPD) of up to 6 target measurable nodes and extra-nodal sites; absence/reduction/no increase in size of non-measured lesions; reduction in length of spleen at least \>50% beyond normal; and no new lesions. Assessment was performed by an IRC according to Lugano classification using CT scan. 95% CI for percentage of responders was calculated using Clopper-Pearson method.

Outcome measures

Outcome measures
Measure	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) n=9 Participants Participants received venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in continued until first 9 participants completed the safety observation window of 28 days. After first 28 days of safety observation (Cycle 1), participants continued to receive venetoclax 600 mg orally once daily up to 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) n=52 Participants Participants received venetoclax 800 mg orally once daily for 1 year along with rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, 10, and 12. Each cycle was of 28 days.	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) n=51 Participants Participants received venetoclax 800 mg orally once daily continuously for 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Containing Cohort: Arm C (BR) n=51 Participants Participants received rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.
Percentage of Participants With OR According to IRC as Per Lugano Classification, Using CT Scan 6-8 weeks after Cycle 6 Day 1	66.7 percentage of participants Interval 29.93 to 92.51	30.2 percentage of participants Interval 18.34 to 44.34	80.4 percentage of participants Interval 66.88 to 90.18	84.3 percentage of participants Interval 71.41 to 92.98
Percentage of Participants With OR According to IRC as Per Lugano Classification, Using CT Scan Year 1	66.7 percentage of participants Interval 29.93 to 92.51	22.6 percentage of participants Interval 12.28 to 36.21	41.2 percentage of participants Interval 27.58 to 55.83	60.8 percentage of participants Interval 46.11 to 74.16

SECONDARY outcome

Timeframe: 4-10 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)

Population: ITT population

OR was defined as CR or PR. CR: reduction of LDi of target nodes/nodal masses to \<=1.5 cm, and no extralymphatic sites of disease; absence of non-measured lesions and new lesions; reduction of enlarged organs to normal; and normal/IHC-negative bone marrow morphology. PR: \>=50% decrease in SPD of up to 6 target measurable nodes and extra-nodal sites; absence/reduction/no increase in size of non-measured lesions; reduction in length of spleen at least \>50% beyond normal; and no new lesions. Assessment was performed by Investigator according to Lugano classification using CT scan. 95% CI for percentage of responders was calculated using Clopper-Pearson method.

Outcome measures

Outcome measures
Measure	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) n=9 Participants Participants received venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in continued until first 9 participants completed the safety observation window of 28 days. After first 28 days of safety observation (Cycle 1), participants continued to receive venetoclax 600 mg orally once daily up to 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) n=52 Participants Participants received venetoclax 800 mg orally once daily for 1 year along with rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, 10, and 12. Each cycle was of 28 days.	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) n=51 Participants Participants received venetoclax 800 mg orally once daily continuously for 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Containing Cohort: Arm C (BR) n=51 Participants Participants received rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.
Percentage of Participants With OR According to Investigator as Per Lugano Classification, Using CT Scan 4-10 weeks after Cycle 6 Day 1	55.6 percentage of participants Interval 21.2 to 86.3	32.1 percentage of participants Interval 19.92 to 46.32	74.5 percentage of participants Interval 60.37 to 85.67	78.4 percentage of participants Interval 64.68 to 88.71
Percentage of Participants With OR According to Investigator as Per Lugano Classification, Using CT Scan Year 1	55.6 percentage of participants Interval 21.2 to 86.3	28.3 percentage of participants Interval 16.79 to 42.35	47.1 percentage of participants Interval 32.93 to 61.54	49.0 percentage of participants Interval 34.75 to 63.4

SECONDARY outcome

Timeframe: Baseline until disease progression or death due to any cause (assessed up to approximately 2.5 years)

Population: ITT population. 'Overall number of participants analyzed'=those evaluable for this outcome measure.

OR was defined as CMR/CR or PMR/PR. CMR, CR, PMR, and PR have been defined in previous endpoints, and are not repeated here due to space constraint. Assessment was performed by Investigator according to Lugano classification using PET scan or CT scan (if PET is missing).

Outcome measures

Outcome measures
Measure	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) n=9 Participants Participants received venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in continued until first 9 participants completed the safety observation window of 28 days. After first 28 days of safety observation (Cycle 1), participants continued to receive venetoclax 600 mg orally once daily up to 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) n=52 Participants Participants received venetoclax 800 mg orally once daily for 1 year along with rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, 10, and 12. Each cycle was of 28 days.	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) n=51 Participants Participants received venetoclax 800 mg orally once daily continuously for 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Containing Cohort: Arm C (BR) n=51 Participants Participants received rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.
Percentage of Participants With OR According to Investigator as Per Lugano Classification, Using PET or CT Scan	66.7 percentage of participants Interval 29.93 to 92.51	36.5 percentage of participants Interval 23.62 to 51.04	80.4 percentage of participants Interval 66.88 to 90.18	80.4 percentage of participants Interval 66.88 to 90.18

SECONDARY outcome

Timeframe: From CMR or PMR until disease progression or death due to any cause (assessed up to approximately 2.5 years)

Population: ITT population. 'Overall number of participants analyzed'=those evaluable for this outcome measure.

DOR was defined as time from CMR/CR or PMR/PR until progressive disease (PD) or death due to any cause. CMR, CR, PMR, and PR have been defined in previous endpoints, and are not repeated here due to space constraint. PD: a score 4 (uptake moderately \>liver) or 5 (uptake markedly \>liver and/or new lesions) with increase in intensity of uptake from baseline on PET 5-PS for individual target nodes/nodal lesions; new FDG-avid foci for extranodal lesions; new FDG-avid foci consistent with lymphoma for new lesions; or new or recurrent FDG-avid foci for bone marrow. Assessment was performed by Investigator according to Lugano classification using PET scan or CT scan (if PET is missing). DOR was calculated using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) n=9 Participants Participants received venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in continued until first 9 participants completed the safety observation window of 28 days. After first 28 days of safety observation (Cycle 1), participants continued to receive venetoclax 600 mg orally once daily up to 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) n=25 Participants Participants received venetoclax 800 mg orally once daily for 1 year along with rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, 10, and 12. Each cycle was of 28 days.	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) n=47 Participants Participants received venetoclax 800 mg orally once daily continuously for 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Containing Cohort: Arm C (BR) n=47 Participants Participants received rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.
Duration of Response (DOR) According to Investigator as Per Lugano Classification, Using PET or CT Scan	32.46 months Interval 9.46 to 32.46	15.79 months Interval 10.15 to 23.49	24.87 months Interval 12.45 to Upper limit of 95% CI could not be calculated due to the low number of participants with event.	15.64 months Interval 12.09 to Upper limit of 95% CI could not be calculated due to the low number of participants with event.

SECONDARY outcome

Timeframe: Baseline until disease progression or death due to any cause (assessed up to approximately 2.5 years)

Population: ITT population

PD: a score 4 (uptake moderately \>liver) or 5 (uptake markedly \>liver and/or new lesions) with increase in intensity of uptake from baseline on PET 5-PS for individual target nodes/nodal lesions; new FDG-avid foci for extranodal lesions; new FDG-avid foci consistent with lymphoma for new lesions; or new or recurrent FDG-avid foci for bone marrow. Assessment was performed by Investigator according to Lugano classification using PET or CT scan.

Outcome measures

Outcome measures
Measure	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) n=9 Participants Participants received venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in continued until first 9 participants completed the safety observation window of 28 days. After first 28 days of safety observation (Cycle 1), participants continued to receive venetoclax 600 mg orally once daily up to 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) n=52 Participants Participants received venetoclax 800 mg orally once daily for 1 year along with rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, 10, and 12. Each cycle was of 28 days.	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) n=51 Participants Participants received venetoclax 800 mg orally once daily continuously for 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Containing Cohort: Arm C (BR) n=51 Participants Participants received rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.
Percentage of Participants With Disease Progression (According to Investigator as Per Lugano Classification, Using PET or CT Scan) or Death	44.4 percentage of participants	86.5 percentage of participants	41.2 percentage of participants	52.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline until disease progression or death due to any cause (assessed up to approximately 2.5 years)

Population: ITT population

PFS was defined as the period from the date of treatment initiation (Safety Run-in and Arm A) or randomization date (Arms B and C) until the date of disease progression, or death due to any cause. PD: a score 4 (uptake moderately \>liver) or 5 (uptake markedly \>liver and/or new lesions) with increase in intensity of uptake from baseline on PET 5-PS for individual target nodes/nodal lesions; new FDG-avid foci for extranodal lesions; new FDG-avid foci consistent with lymphoma for new lesions; or new or recurrent FDG-avid foci for bone marrow. Assessment was performed by Investigator according to Lugano classification using PET or CT scan. PFS was calculated using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) n=9 Participants Participants received venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in continued until first 9 participants completed the safety observation window of 28 days. After first 28 days of safety observation (Cycle 1), participants continued to receive venetoclax 600 mg orally once daily up to 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) n=52 Participants Participants received venetoclax 800 mg orally once daily for 1 year along with rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, 10, and 12. Each cycle was of 28 days.	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) n=51 Participants Participants received venetoclax 800 mg orally once daily continuously for 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Containing Cohort: Arm C (BR) n=51 Participants Participants received rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.
Progression-Free Survival (PFS) According to Investigator as Per Lugano Classification, Using PET or CT Scan	35.09 months Interval 12.78 to 35.09	6.57 months Interval 6.18 to 12.25	27.63 months Interval 16.07 to Upper limit of 95% CI could not be calculated due to the low number of participants with event.	18.43 months Interval 16.92 to Upper limit of 95% CI could not be calculated due to the low number of participants with event.

SECONDARY outcome

Timeframe: Baseline until disease progression, death, or start of a new anti-lymphoma therapy whichever occurred first (assessed up to approximately 2.5 years)

Population: ITT population

Outcome measures

Outcome measures
Measure	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) n=9 Participants Participants received venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in continued until first 9 participants completed the safety observation window of 28 days. After first 28 days of safety observation (Cycle 1), participants continued to receive venetoclax 600 mg orally once daily up to 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) n=52 Participants Participants received venetoclax 800 mg orally once daily for 1 year along with rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, 10, and 12. Each cycle was of 28 days.	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) n=51 Participants Participants received venetoclax 800 mg orally once daily continuously for 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Containing Cohort: Arm C (BR) n=51 Participants Participants received rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.
Percentage of Participants With Disease Progression (According to Investigator as Per Lugano Classification, Using PET or CT Scan), Death, or Start of a New Anti-lymphoma Therapy	44.4 percentage of participants	86.5 percentage of participants	41.2 percentage of participants	52.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline until disease progression, death, or start of a new anti-lymphoma therapy whichever occurred first (assessed up to approximately 2.5 years)

Population: ITT population

EFS was defined as the period from the date of treatment initiation (Safety Run-in and Arm A) or randomization date (Arms B and C) to the date of disease progression, death, or start of a new anti-lymphoma therapy whichever occurred first. PD: a score 4 (uptake moderately \>liver) or 5 (uptake markedly \>liver and/or new lesions) with increase in intensity of uptake from baseline on PET 5-PS for individual target nodes/nodal lesions; new FDG-avid foci for extranodal lesions; new FDG-avid foci consistent with lymphoma for new lesions; or new or recurrent FDG-avid foci for bone marrow. Assessment was performed by Investigator according to Lugano classification using PET or CT scan. EFS was calculated using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) n=9 Participants Participants received venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in continued until first 9 participants completed the safety observation window of 28 days. After first 28 days of safety observation (Cycle 1), participants continued to receive venetoclax 600 mg orally once daily up to 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) n=52 Participants Participants received venetoclax 800 mg orally once daily for 1 year along with rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, 10, and 12. Each cycle was of 28 days.	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) n=51 Participants Participants received venetoclax 800 mg orally once daily continuously for 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Containing Cohort: Arm C (BR) n=51 Participants Participants received rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.
Event-Free Survival (EFS) According to Investigator as Per Lugano Classification, Using PET or CT Scan	35.09 months Interval 12.78 to 35.09	6.57 months Interval 6.18 to 12.25	27.63 months Interval 16.07 to Upper limit of 95% CI could not be calculated due to the low number of participants with event.	18.43 months Interval 16.92 to Upper limit of 95% CI could not be calculated due to the low number of participants with event.

SECONDARY outcome

Timeframe: Baseline until death due to any cause (assessed up to approximately 2.5 years

Population: ITT population

Outcome measures

Outcome measures
Measure	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) n=9 Participants Participants received venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in continued until first 9 participants completed the safety observation window of 28 days. After first 28 days of safety observation (Cycle 1), participants continued to receive venetoclax 600 mg orally once daily up to 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) n=52 Participants Participants received venetoclax 800 mg orally once daily for 1 year along with rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, 10, and 12. Each cycle was of 28 days.	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) n=51 Participants Participants received venetoclax 800 mg orally once daily continuously for 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Containing Cohort: Arm C (BR) n=51 Participants Participants received rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.
Percentage of Participants Who Died Due to Any Cause	0 percentage of participants	5.8 percentage of participants	2.0 percentage of participants	3.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline until death due to any cause (assessed up to approximately 2.5 years)

Population: ITT population

OS was defined as the period from the date of treatment initiation (Safety Run-in and Arm A) or randomization date (Arms B and C) to death due to any cause. For participants who are alive, OS was censored at the last contact. OS was calculated using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) n=9 Participants Participants received venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in continued until first 9 participants completed the safety observation window of 28 days. After first 28 days of safety observation (Cycle 1), participants continued to receive venetoclax 600 mg orally once daily up to 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) n=52 Participants Participants received venetoclax 800 mg orally once daily for 1 year along with rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, 10, and 12. Each cycle was of 28 days.	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) n=51 Participants Participants received venetoclax 800 mg orally once daily continuously for 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Containing Cohort: Arm C (BR) n=51 Participants Participants received rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.
Overall Survival (OS)	NA months Median and corresponding 95% CI could not be estimated due to higher number of censored participants.	NA months Median and corresponding 95% CI could not be estimated due to higher number of censored participants.	NA months Median and corresponding 95% CI could not be estimated due to higher number of censored participants.	NA months Median and corresponding 95% CI could not be estimated due to higher number of censored participants.

SECONDARY outcome

Timeframe: Pre-dose (within 30 minutes), and 2, 4, 6, 8 hours post-dose on Cycle 1 Day 1; pre-dose (within 30 minutes) on Cycle 1 Days 8, 15, 22; pre-dose (within 30 minutes) and 4 hours post-dose on Day 1 of Cycles 4 and 6 (Cycle length = 28 days)

Population: The data could not be collected as the timepoints for pharmacokinetics collection and the daily dosing of venetoclax did not permit an assessment of CL.

CL is a quantitative measure of the rate at which a drug substance is removed from the body.

Outcome measures

Outcome data not reported

SECONDARY outcome

Population: The data could not be collected as the timepoints for pharmacokinetics collection and the daily dosing of venetoclax did not permit an assessment of Vd.

Vd was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

Outcome measures

Outcome data not reported

SECONDARY outcome

Population: Pharmacokinetic-evaluable population included all enrolled participants with available pharmacokinetic data for venetoclax.

Outcome measures

Outcome measures
Measure	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) n=9 Participants Participants received venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in continued until first 9 participants completed the safety observation window of 28 days. After first 28 days of safety observation (Cycle 1), participants continued to receive venetoclax 600 mg orally once daily up to 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) n=51 Participants Participants received venetoclax 800 mg orally once daily for 1 year along with rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, 10, and 12. Each cycle was of 28 days.	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) n=46 Participants Participants received venetoclax 800 mg orally once daily continuously for 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Containing Cohort: Arm C (BR) Participants received rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.
Time to Maximum Plasma Concentration (Tmax) of Venetoclax	8.00 hours Interval 4.0 to 8.08	6.00 hours Interval 1.95 to 8.18	6.21 hours Interval 1.98 to 9.22	—

SECONDARY outcome

Population: Pharmacokinetic-evaluable population

Outcome measures

Outcome measures
Measure	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) n=9 Participants Participants received venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in continued until first 9 participants completed the safety observation window of 28 days. After first 28 days of safety observation (Cycle 1), participants continued to receive venetoclax 600 mg orally once daily up to 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) n=51 Participants Participants received venetoclax 800 mg orally once daily for 1 year along with rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, 10, and 12. Each cycle was of 28 days.	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) n=46 Participants Participants received venetoclax 800 mg orally once daily continuously for 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Containing Cohort: Arm C (BR) Participants received rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.
Maximum Plasma Concentration (Cmax) of Venetoclax	1350 nanograms per milliliter (ng/mL) Standard Deviation 427	1220 nanograms per milliliter (ng/mL) Standard Deviation 478	1340 nanograms per milliliter (ng/mL) Standard Deviation 460	—

SECONDARY outcome

Population: Pharmacokinetic-evaluable population

Area under the plasma concentration versus time curve from zero to the last measured concentration (AUClast).

Outcome measures

Outcome measures
Measure	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) n=9 Participants Participants received venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in continued until first 9 participants completed the safety observation window of 28 days. After first 28 days of safety observation (Cycle 1), participants continued to receive venetoclax 600 mg orally once daily up to 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) n=51 Participants Participants received venetoclax 800 mg orally once daily for 1 year along with rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, 10, and 12. Each cycle was of 28 days.	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) n=46 Participants Participants received venetoclax 800 mg orally once daily continuously for 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Containing Cohort: Arm C (BR) Participants received rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.
Area Under the Plasma Concentration-Time Curve From Time 0 to Last Observed Concentration (AUClast) of Venetoclax	5310 hours*ng/mL Standard Deviation 1730	4950 hours*ng/mL Standard Deviation 1950	5500 hours*ng/mL Standard Deviation 2270	—

SECONDARY outcome

Population: Pharmacokinetic-evaluable population. 'Overall number of participants analyzed'=those evaluable for this outcome measure.

Area under the plasma concentration versus time curve from time 0 (pre-dose) to 8 hours post dose (AUC0-8h).

Outcome measures

Outcome measures
Measure	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) n=6 Participants Participants received venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in continued until first 9 participants completed the safety observation window of 28 days. After first 28 days of safety observation (Cycle 1), participants continued to receive venetoclax 600 mg orally once daily up to 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) n=30 Participants Participants received venetoclax 800 mg orally once daily for 1 year along with rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, 10, and 12. Each cycle was of 28 days.	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) n=23 Participants Participants received venetoclax 800 mg orally once daily continuously for 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.	Chemotherapy-Containing Cohort: Arm C (BR) Participants received rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.
Area Under the Plasma Concentration-Time Curve From Time 0 to 8 Hours Post Dose (AUC0-8h) of Venetoclax	5240 hours*ng/mL Standard Deviation 1860	4820 hours*ng/mL Standard Deviation 1980	5330 hours*ng/mL Standard Deviation 2270	—

Adverse Events

Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)

Serious events: 4 serious events

Other events: 9 other events

Deaths: 0 deaths

Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)

Serious events: 16 serious events

Other events: 49 other events

Deaths: 0 deaths

Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)

Serious events: 26 serious events

Other events: 49 other events

Deaths: 0 deaths

Chemotherapy-Containing Cohort: Arm C (BR)

Serious events: 12 serious events

Other events: 48 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER