Trial Outcomes & Findings for A Study to Compare the Efficacy and Safety of a Combined Regimen of Venetoclax and Obinutuzumab Versus Fludarabine, Cyclophosphamide, and Rituximab (FCR)/ Bendamustine And Rituximab (BR) in FIT Patients With Previously Untreated Chronic Lymphocytic Leukemia (CLL) Without DEL (17P) or TP53 Mutation (NCT NCT04285567)

Last Updated: 2025-10-08

Results Overview

MRD response rate was determined as the percentage of participants with MRD-negativity measured in the PB using NGS using a cutoff of \< 10\^-4. MRD was considered negative if the result was \< 1 CLL cell in 10,000 leukocytes. Percentages have been rounded off to the nearest decimal point.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

166 participants

Primary outcome timeframe

At Month 15

Results posted on

2025-10-08

Participant Flow

A total of 166 participants took part in this study which was conducted at 38 investigative sites in France, Italy, Australia, Spain, and the United States. The study is still ongoing.

Participants with previously untreated chronic lymphocytic leukemia (CLL) without del (17p) or tumor protein p53 (TP53) mutation were randomized in a 1:1 ratio to receive either venetoclax + obinutuzumab (VEN+G) or fludarabine, cyclophosphamide, and rituximab/bendamustine and rituximab (FCR/BR). All participants in FCR/BR arm were eligible for treatment with BR, whereas only participants ≤ 65 years were eligible for FCR. The choice between FCR or BR was at the investigator's discretion.

Participant milestones

Participant milestones
Measure	Arm A: VEN+G Participants received obinutuzumab, 1000 milligrams (mg), as intravenous (IV) infusion on Days 1 (and 2), 8, and 15 of Cycle 1 and Day 1 of Cycles 2-6. Participants also received venetoclax, with a 5-week ramp-up period (20 mg \[Cycle 1 Days 22-28\], 50 mg \[Cycle 2 Days 1-7\], 100 mg \[Cycle 2 Days 8-14\], 200 mg \[Cycle 2 Days 15-21\], 400 mg \[Cycle 2 Days 22-28\]) administered orally, once a day (QD). After the 5-week ramp-up period, participants received venetoclax, 400 mg, orally, QD from Cycle 3 Day 1 until the end of Cycle 12. (1 cycle = 28 days).	Arm B: FCR/BR Participants received rituximab (375 milligrams per meter square \[mg/m\^2\] in Cycle 1 and 500 mg/m\^2 in Cycles 2-6), on Day 1 of each cycle, plus fludarabine 25 mg/m\^2 and cyclophosphamide 250 mg/m\^2 on Days 1, 2, and 3 of each cycle as IV infusion up to Cycle 6. Participants alternatively received bendamustine 90 mg/m\^2 on Days 1 and 2 of Cycles 1-6 plus rituximab 375 mg/m\^2 on Day 1 of Cycle 1 and 500 mg/m\^2 on Day 1 of Cycles 2-6. (1 cycle = 28 days).
Overall Study STARTED	80	86
Overall Study Safety Population	77	85
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	80	86

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A: VEN+G Participants received obinutuzumab, 1000 milligrams (mg), as intravenous (IV) infusion on Days 1 (and 2), 8, and 15 of Cycle 1 and Day 1 of Cycles 2-6. Participants also received venetoclax, with a 5-week ramp-up period (20 mg \[Cycle 1 Days 22-28\], 50 mg \[Cycle 2 Days 1-7\], 100 mg \[Cycle 2 Days 8-14\], 200 mg \[Cycle 2 Days 15-21\], 400 mg \[Cycle 2 Days 22-28\]) administered orally, once a day (QD). After the 5-week ramp-up period, participants received venetoclax, 400 mg, orally, QD from Cycle 3 Day 1 until the end of Cycle 12. (1 cycle = 28 days).	Arm B: FCR/BR Participants received rituximab (375 milligrams per meter square \[mg/m\^2\] in Cycle 1 and 500 mg/m\^2 in Cycles 2-6), on Day 1 of each cycle, plus fludarabine 25 mg/m\^2 and cyclophosphamide 250 mg/m\^2 on Days 1, 2, and 3 of each cycle as IV infusion up to Cycle 6. Participants alternatively received bendamustine 90 mg/m\^2 on Days 1 and 2 of Cycles 1-6 plus rituximab 375 mg/m\^2 on Day 1 of Cycle 1 and 500 mg/m\^2 on Day 1 of Cycles 2-6. (1 cycle = 28 days).
Overall Study Death	3	3
Overall Study Lost to Follow-up	1	1
Overall Study Reason Not Specified	1	1
Overall Study Physician Decision	2	1
Overall Study Withdrawal by Subject	2	6
Overall Study Adverse Event	1	0
Overall Study Participants Ongoing in Follow-up	70	74

Baseline Characteristics

A Study to Compare the Efficacy and Safety of a Combined Regimen of Venetoclax and Obinutuzumab Versus Fludarabine, Cyclophosphamide, and Rituximab (FCR)/ Bendamustine And Rituximab (BR) in FIT Patients With Previously Untreated Chronic Lymphocytic Leukemia (CLL) Without DEL (17P) or TP53 Mutation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A: VEN+G n=80 Participants Participants received obinutuzumab, 1000 mg, as IV infusion on Days 1 (and 2), 8, and 15 of Cycle 1 and Day 1 of Cycles 2-6. Participants also received venetoclax, with a 5-week ramp-up period (20 mg \[Cycle 1 Days 22-28\], 50 mg \[Cycle 2 Days 1-7\], 100 mg \[Cycle 2 Days 8-14\], 200 mg \[Cycle 2 Days 15-21\], 400 mg \[Cycle 2 Days 22-28\]) administered orally, QD. After the 5-week ramp-up period, participants received venetoclax, 400 mg, orally, QD from Cycle 3 Day 1 until the end of Cycle 12. (1 cycle = 28 days).	Arm B: FCR/BR n=86 Participants Participants received rituximab (375 mg/m\^2 in Cycle 1 and 500 mg/m\^2 in Cycles 2-6), on Day 1 of each cycle, plus fludarabine 25 mg/m\^2 and cyclophosphamide 250 mg/m\^2 on Days 1, 2, and 3 of each cycle as IV infusion up to Cycle 6. Participants alternatively received bendamustine 90 mg/m\^2 on Days 1 and 2 of Cycles 1-6 plus rituximab 375 mg/m\^2 on Day 1 of Cycle 1 and 500 mg/m\^2 on Day 1 of Cycles 2-6. (1 cycle = 28 days).	Total n=166 Participants Total of all reporting groups
Age, Continuous	61.5 years STANDARD_DEVIATION 9.1 • n=5 Participants	61.0 years STANDARD_DEVIATION 8.6 • n=7 Participants	61.2 years STANDARD_DEVIATION 8.8 • n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	29 Participants n=7 Participants	54 Participants n=5 Participants
Sex: Female, Male Male	55 Participants n=5 Participants	57 Participants n=7 Participants	112 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	50 Participants n=5 Participants	62 Participants n=7 Participants	112 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	25 Participants n=5 Participants	19 Participants n=7 Participants	44 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	58 Participants n=5 Participants	73 Participants n=7 Participants	131 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	20 Participants n=5 Participants	11 Participants n=7 Participants	31 Participants n=5 Participants

PRIMARY outcome

Timeframe: At Month 15

Population: FAS included all randomized participants, analyzed according to the treatment to which they were randomized.

Outcome measures

Outcome measures
Measure	Arm A: VEN+G n=80 Participants Participants received obinutuzumab, 1000 mg, as IV infusion on Days 1 (and 2), 8, and 15 of Cycle 1 and Day 1 of Cycles 2-6. Participants also received venetoclax, with a 5-week ramp-up period (20 mg \[Cycle 1 Days 22-28\], 50 mg \[Cycle 2 Days 1-7\], 100 mg \[Cycle 2 Days 8-14\], 200 mg \[Cycle 2 Days 15-21\], 400 mg \[Cycle 2 Days 22-28\]) administered orally, QD. After the 5-week ramp-up period, participants received venetoclax, 400 mg, orally, QD from Cycle 3 Day 1 until the end of Cycle 12. (1 cycle = 28 days).	Arm B: FCR/BR n=86 Participants Participants received rituximab (375 mg/m\^2 in Cycle 1 and 500 mg/m\^2 in Cycles 2-6), on Day 1 of each cycle, plus fludarabine 25 mg/m\^2 and cyclophosphamide 250 mg/m\^2 on Days 1, 2, and 3 of each cycle as IV infusion up to Cycle 6. Participants alternatively received bendamustine 90 mg/m\^2 on Days 1 and 2 of Cycles 1-6 plus rituximab 375 mg/m\^2 on Day 1 of Cycle 1 and 500 mg/m\^2 on Day 1 of Cycles 2-6. (1 cycle = 28 days).
Minimal Residual Disease (MRD) Response Rate Measured in Peripheral Blood (PB) Using Next Generation Sequencing (NGS)	81.3 percentage of participants Interval 70.97 to 89.11	54.7 percentage of participants Interval 43.55 to 65.42

SECONDARY outcome

Timeframe: Up to approximately 74 months

PFS was defined as the time from randomization to the first occurrence of disease progression (PD), or death from any cause. PD was assessed by the investigators using the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria. PD was defined as any one of the following: Appearance of any new lesion such as enlarged lymph nodes (≥ 1.5 centimeters \[cm\]); increase by ≥ 50% in greatest diameter of any previous site (≥ 1.5 cm); increase in the spleen/liver size by ≥ 50% or de novo appearance of splenomegaly/hepatomegaly; increase in blood lymphocytes by 50% or more with at least 5x10\^9/litres (L) B lymphocytes; transformation to a more aggressive histology; occurrence of cytopenia; posttreatment: progression of any cytopenia, documented by a decrease of hemoglobin (Hb) ≥ 2 grams per deciliter (g/dL) or 10 g/dL, or by a decrease of platelet counts ≥ 50%/100x10\^9/L, which occurs at least 3 months after treatment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: VEN+G: From Cycle 1 Day 1 up to 15 months; FCR/BR: From Cycle 1 Day 1 up to 9 months (1 cycle=28 days)

Population: FAS included all randomized participants, analyzed according to the treatment to which they were randomized.

Outcome measures

Outcome measures
Measure	Arm A: VEN+G n=80 Participants Participants received obinutuzumab, 1000 mg, as IV infusion on Days 1 (and 2), 8, and 15 of Cycle 1 and Day 1 of Cycles 2-6. Participants also received venetoclax, with a 5-week ramp-up period (20 mg \[Cycle 1 Days 22-28\], 50 mg \[Cycle 2 Days 1-7\], 100 mg \[Cycle 2 Days 8-14\], 200 mg \[Cycle 2 Days 15-21\], 400 mg \[Cycle 2 Days 22-28\]) administered orally, QD. After the 5-week ramp-up period, participants received venetoclax, 400 mg, orally, QD from Cycle 3 Day 1 until the end of Cycle 12. (1 cycle = 28 days).	Arm B: FCR/BR n=86 Participants Participants received rituximab (375 mg/m\^2 in Cycle 1 and 500 mg/m\^2 in Cycles 2-6), on Day 1 of each cycle, plus fludarabine 25 mg/m\^2 and cyclophosphamide 250 mg/m\^2 on Days 1, 2, and 3 of each cycle as IV infusion up to Cycle 6. Participants alternatively received bendamustine 90 mg/m\^2 on Days 1 and 2 of Cycles 1-6 plus rituximab 375 mg/m\^2 on Day 1 of Cycle 1 and 500 mg/m\^2 on Day 1 of Cycles 2-6. (1 cycle = 28 days).
MRD Response Rate in PB of FCR/BR Compared With VEN+G at the End of Treatment Response Visit	81.3 percentage of participants Interval 70.97 to 89.11	60.5 percentage of participants Interval 49.34 to 70.85

SECONDARY outcome

Timeframe: VEN+G: From Cycle 1 Day 1 up to 15 months; FCR/BR: From Cycle 1 Day 1 up to 9 months (1 cycle=28 days)

Population: FAS included all randomized participants, analyzed according to the treatment to which they were randomized. Percentages have been rounded off to the nearest decimal point.

MRD response rate=percentage of participants with MRD-negativity measured in BM using NGS (cutoff of \<10\^-4). MRD negativity=\<1 CLL cell in 10,000 leukocytes. MRD in BM was assessed for participants with complete response (CR)/CR with incomplete blood count recovery (CRi) \& partial response (PR). CR=PB lymphocytes \<4x10\^9 /L; Absence of significant lymphadenopathy (nodes \<1.5 cm in longest diameter); no hepatomegaly/splenomegaly; absence of disease/constitutional symptoms; BM at least normocellular for age, ≤30% of nucleated cells being lymphocytes. CRi=fulfilling CR criteria but with persistent anemia/thrombocytopenia/neutropenia. PR= ≥50% decrease in PB lymphocyte count from pre-treatment value; ≥50% reduction in lymphadenopathy (sum of longest diameter of up to 6 largest lymph nodes by physical exam \& 50% reduction in the sum of product of the diameter of up to 6 largest lymph nodes); ≥50% reduction of liver/spleen enlargement/normalization in size, if enlarged at baseline.

Outcome measures

Outcome measures
Measure	Arm A: VEN+G n=80 Participants Participants received obinutuzumab, 1000 mg, as IV infusion on Days 1 (and 2), 8, and 15 of Cycle 1 and Day 1 of Cycles 2-6. Participants also received venetoclax, with a 5-week ramp-up period (20 mg \[Cycle 1 Days 22-28\], 50 mg \[Cycle 2 Days 1-7\], 100 mg \[Cycle 2 Days 8-14\], 200 mg \[Cycle 2 Days 15-21\], 400 mg \[Cycle 2 Days 22-28\]) administered orally, QD. After the 5-week ramp-up period, participants received venetoclax, 400 mg, orally, QD from Cycle 3 Day 1 until the end of Cycle 12. (1 cycle = 28 days).	Arm B: FCR/BR n=86 Participants Participants received rituximab (375 mg/m\^2 in Cycle 1 and 500 mg/m\^2 in Cycles 2-6), on Day 1 of each cycle, plus fludarabine 25 mg/m\^2 and cyclophosphamide 250 mg/m\^2 on Days 1, 2, and 3 of each cycle as IV infusion up to Cycle 6. Participants alternatively received bendamustine 90 mg/m\^2 on Days 1 and 2 of Cycles 1-6 plus rituximab 375 mg/m\^2 on Day 1 of Cycle 1 and 500 mg/m\^2 on Day 1 of Cycles 2-6. (1 cycle = 28 days).
MRD Response Rate in Bone Marrow (BM) of FCR/BR Compared With VEN+G at the End of Treatment Response Visit	70.0 percentage of participants Interval 58.72 to 79.74	38.4 percentage of participants Interval 28.08 to 49.49

SECONDARY outcome

Timeframe: At Month 15

Population: FAS included all randomized participants, analyzed according to the treatment to which they were randomized. Percentages have been rounded off to the nearest decimal point.

ORR was defined as the percentage of participants with overall response (OR) of CR, CRi, and PR as determined by the investigator according to the iwCLL guidelines. CR was defined as PB lymphocytes \<4x10\^9 /L; absence of significant lymphadenopathy (nodes \<1.5 cm in longest diameter \[LD\]); no hepatomegaly/splenomegaly; absence of disease/constitutional symptoms; BM at least normocellular for age, ≤30% of nucleated cells being lymphocytes. CRi was defined as fulfilling CR criteria but with persistent anemia/thrombocytopenia/neutropenia. PR was defined as ≥50% decrease in PB lymphocyte count from pre-treatment value; ≥50% reduction in lymphadenopathy sum of longest diameter of up to 6 largest lymph nodes by physical exam and 50% reduction in the sum of product of the diameter of up to 6 largest lymph nodes); ≥50% reduction of liver/spleen enlargement/normalization in size, if enlarged at baseline.

Outcome measures

Outcome measures
Measure	Arm A: VEN+G n=80 Participants Participants received obinutuzumab, 1000 mg, as IV infusion on Days 1 (and 2), 8, and 15 of Cycle 1 and Day 1 of Cycles 2-6. Participants also received venetoclax, with a 5-week ramp-up period (20 mg \[Cycle 1 Days 22-28\], 50 mg \[Cycle 2 Days 1-7\], 100 mg \[Cycle 2 Days 8-14\], 200 mg \[Cycle 2 Days 15-21\], 400 mg \[Cycle 2 Days 22-28\]) administered orally, QD. After the 5-week ramp-up period, participants received venetoclax, 400 mg, orally, QD from Cycle 3 Day 1 until the end of Cycle 12. (1 cycle = 28 days).	Arm B: FCR/BR n=86 Participants Participants received rituximab (375 mg/m\^2 in Cycle 1 and 500 mg/m\^2 in Cycles 2-6), on Day 1 of each cycle, plus fludarabine 25 mg/m\^2 and cyclophosphamide 250 mg/m\^2 on Days 1, 2, and 3 of each cycle as IV infusion up to Cycle 6. Participants alternatively received bendamustine 90 mg/m\^2 on Days 1 and 2 of Cycles 1-6 plus rituximab 375 mg/m\^2 on Day 1 of Cycle 1 and 500 mg/m\^2 on Day 1 of Cycles 2-6. (1 cycle = 28 days).
Objective Response Rate (ORR)	88.8 percentage of participants Interval 79.72 to 94.72	79.1 percentage of participants Interval 68.95 to 87.1

SECONDARY outcome

Timeframe: At Month 15

Population: FAS included all randomized participants, analyzed according to the treatment to which they were randomized.

CR rate was defined as the percentage of participants with CR or CRi. CR/CRi were defined according to the iwCLL guidelines. CR was defined as one of the following: PB lymphocytes (evaluated by blood and differential count) below 4 x 10\^9 /L; absence of significant lymphadenopathy (nodes \< 1.5 cm in LD or any extra nodal disease); no hepatomegaly; no splenomegaly; absence of disease or constitutional symptoms; BM at least normocellular for age, ≤30% of nucleated cells being lymphocytes. CRi was defined as participants fulfilling CR criteria but had persistent anemia, thrombocytopenia, or neutropenia. Percentages have been rounded off to the nearest decimal point.

Outcome measures

Outcome measures
Measure	Arm A: VEN+G n=80 Participants Participants received obinutuzumab, 1000 mg, as IV infusion on Days 1 (and 2), 8, and 15 of Cycle 1 and Day 1 of Cycles 2-6. Participants also received venetoclax, with a 5-week ramp-up period (20 mg \[Cycle 1 Days 22-28\], 50 mg \[Cycle 2 Days 1-7\], 100 mg \[Cycle 2 Days 8-14\], 200 mg \[Cycle 2 Days 15-21\], 400 mg \[Cycle 2 Days 22-28\]) administered orally, QD. After the 5-week ramp-up period, participants received venetoclax, 400 mg, orally, QD from Cycle 3 Day 1 until the end of Cycle 12. (1 cycle = 28 days).	Arm B: FCR/BR n=86 Participants Participants received rituximab (375 mg/m\^2 in Cycle 1 and 500 mg/m\^2 in Cycles 2-6), on Day 1 of each cycle, plus fludarabine 25 mg/m\^2 and cyclophosphamide 250 mg/m\^2 on Days 1, 2, and 3 of each cycle as IV infusion up to Cycle 6. Participants alternatively received bendamustine 90 mg/m\^2 on Days 1 and 2 of Cycles 1-6 plus rituximab 375 mg/m\^2 on Day 1 of Cycle 1 and 500 mg/m\^2 on Day 1 of Cycles 2-6. (1 cycle = 28 days).
CR Rate	50.0 percentage of participants Interval 38.6 to 61.4	32.6 percentage of participants Interval 22.84 to 43.52

SECONDARY outcome

Timeframe: At Month 15

Population: FAS included all randomized participants, analyzed according to the treatment to which they were randomized. Overall number analyzed is the number of participants with CR/CRi.

MRD response rate was determined as the percentage of participants (with a CR/CRi) with MRD-negativity measured in the PB using NGS using a cutoff of \< 10\^-4. MRD was considered negative if the result was \< 1 CLL cell in 10,000 leukocytes. CR/CRi were defined according to the iwCLL guidelines. CR was defined as one of the following: PB lymphocytes below 4 x 10\^9 /L; absence of significant lymphadenopathy (nodes \< 1.5 cm in LD or any extra nodal disease); no hepatomegaly; no splenomegaly; absence of disease or constitutional symptoms; BM at least normocellular for age, ≤30% of nucleated cells being lymphocytes. CRi was defined as participants fulfilling CR criteria but had persistent anemia, thrombocytopenia, or neutropenia. Percentages have been rounded off to the nearest decimal point.

Outcome measures

Outcome measures
Measure	Arm A: VEN+G n=40 Participants Participants received obinutuzumab, 1000 mg, as IV infusion on Days 1 (and 2), 8, and 15 of Cycle 1 and Day 1 of Cycles 2-6. Participants also received venetoclax, with a 5-week ramp-up period (20 mg \[Cycle 1 Days 22-28\], 50 mg \[Cycle 2 Days 1-7\], 100 mg \[Cycle 2 Days 8-14\], 200 mg \[Cycle 2 Days 15-21\], 400 mg \[Cycle 2 Days 22-28\]) administered orally, QD. After the 5-week ramp-up period, participants received venetoclax, 400 mg, orally, QD from Cycle 3 Day 1 until the end of Cycle 12. (1 cycle = 28 days).	Arm B: FCR/BR n=28 Participants Participants received rituximab (375 mg/m\^2 in Cycle 1 and 500 mg/m\^2 in Cycles 2-6), on Day 1 of each cycle, plus fludarabine 25 mg/m\^2 and cyclophosphamide 250 mg/m\^2 on Days 1, 2, and 3 of each cycle as IV infusion up to Cycle 6. Participants alternatively received bendamustine 90 mg/m\^2 on Days 1 and 2 of Cycles 1-6 plus rituximab 375 mg/m\^2 on Day 1 of Cycle 1 and 500 mg/m\^2 on Day 1 of Cycles 2-6. (1 cycle = 28 days).
MRD Response Rate in PB of Participants With a CR/CRi at the End of Treatment Visit	97.5 percentage of participants Interval 86.84 to 99.94	78.6 percentage of participants Interval 59.05 to 91.7

SECONDARY outcome

Timeframe: VEN+G: From Cycle 1 Day 1 up to 15 months; FCR/BR: From Cycle 1 Day 1 up to 9 months (1 cycle=28 days)

Population: FAS included all randomized participants, analyzed according to the treatment to which they were randomized. Overall number analyzed is the number of participants with CR/CRi.

MRD response rate was determined as the percentage of participants (with CR/CRi) with MRD-negativity measured in the BM using NGS using a cutoff of \< 10\^-4. MRD was considered negative if the result was \< 1 CLL cell in 10,000 leukocytes. CR/CRi were defined according to the iwCLL guidelines. CR was defined as one of the following: PB lymphocytes below 4 x 10\^9 /L; absence of significant lymphadenopathy (nodes \< 1.5 cm in LD or any extra nodal disease); no hepatomegaly; no splenomegaly; absence of disease or constitutional symptoms; BM at least normocellular for age, ≤30% of nucleated cells being lymphocytes. CRi was defined as participants fulfilling CR criteria with CR but had persistent anemia, thrombocytopenia, or neutropenia. Percentages have been rounded off to the nearest decimal point.

Outcome measures

Outcome measures
Measure	Arm A: VEN+G n=40 Participants Participants received obinutuzumab, 1000 mg, as IV infusion on Days 1 (and 2), 8, and 15 of Cycle 1 and Day 1 of Cycles 2-6. Participants also received venetoclax, with a 5-week ramp-up period (20 mg \[Cycle 1 Days 22-28\], 50 mg \[Cycle 2 Days 1-7\], 100 mg \[Cycle 2 Days 8-14\], 200 mg \[Cycle 2 Days 15-21\], 400 mg \[Cycle 2 Days 22-28\]) administered orally, QD. After the 5-week ramp-up period, participants received venetoclax, 400 mg, orally, QD from Cycle 3 Day 1 until the end of Cycle 12. (1 cycle = 28 days).	Arm B: FCR/BR n=28 Participants Participants received rituximab (375 mg/m\^2 in Cycle 1 and 500 mg/m\^2 in Cycles 2-6), on Day 1 of each cycle, plus fludarabine 25 mg/m\^2 and cyclophosphamide 250 mg/m\^2 on Days 1, 2, and 3 of each cycle as IV infusion up to Cycle 6. Participants alternatively received bendamustine 90 mg/m\^2 on Days 1 and 2 of Cycles 1-6 plus rituximab 375 mg/m\^2 on Day 1 of Cycle 1 and 500 mg/m\^2 on Day 1 of Cycles 2-6. (1 cycle = 28 days).
MRD Response Rate in BM of Participants With a CR/CRi at the End of Treatment Visit	87.5 percentage of participants Interval 73.2 to 95.81	60.7 percentage of participants Interval 40.58 to 78.5

SECONDARY outcome

Timeframe: Up to approximately 74 months

DOR was defined as the time from the first occurrence of a documented OR (CR, CRi and PR) to the time of PD as determined by the investigator, or death from any cause, whichever occurs first. CR, CRi, PR, and PD were defined according to the iwCLL guidelines. PD was defined as any one of the following: appearance of any new lesion such as enlarged lymph nodes (≥ 1.5 cm); increase by ≥ 50% in greatest diameter of any previous site (≥ 1.5 cm); increase in the spleen/liver size by ≥ 50% or de novo appearance of splenomegaly/hepatomegaly; increase in blood lymphocytes by 50% or more with at least 5x10\^9/L B lymphocytes; transformation to a more aggressive histology; occurrence of cytopenia; posttreatment: progression of any cytopenia, documented by a decrease of Hb ≥ 2 g/dL or 10 g/dL, or by a decrease of platelet counts ≥ 50%/100x10\^9/L, which occurs at least 3 months after treatment. CR, CRi and PR were defined as outlined in the description for ORR outcome measure (OM) number 5.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Month 15

Population: FAS included all randomized participants, analyzed according to the treatment to which they were randomized.

BOR=percentage of participants with CR/CRi/PR/stable disease (SD)/PD per the investigator. Participants with best response as CR/CRi/PR were considered responders while those reaching SD/PD were non-responders. SD=participants who have not achieved a CR or a PR, or who have not exhibited PD. PD=any one of the following: appearance of any new lesion such as enlarged lymph nodes (≥ 1.5 cm); increase by ≥ 50% in greatest diameter of any previous site (≥ 1.5 cm); increase in the spleen/liver size by ≥ 50% or de novo appearance of splenomegaly/hepatomegaly; increase in blood lymphocytes by 50% or more with at least 5x10\^9/L B lymphocytes; transformation to a more aggressive histology; occurrence of cytopenia; posttreatment: progression of any cytopenia, documented by a decrease of Hb ≥ 2 g/dL or 10 g/dL, or by a decrease of platelet counts ≥ 50%/100x10\^9/L, which occurs at least 3 months after treatment. CR, CRi and PR were defined as outlined in the description for ORR, OM number 5.

Outcome measures

Outcome measures
Measure	Arm A: VEN+G n=80 Participants Participants received obinutuzumab, 1000 mg, as IV infusion on Days 1 (and 2), 8, and 15 of Cycle 1 and Day 1 of Cycles 2-6. Participants also received venetoclax, with a 5-week ramp-up period (20 mg \[Cycle 1 Days 22-28\], 50 mg \[Cycle 2 Days 1-7\], 100 mg \[Cycle 2 Days 8-14\], 200 mg \[Cycle 2 Days 15-21\], 400 mg \[Cycle 2 Days 22-28\]) administered orally, QD. After the 5-week ramp-up period, participants received venetoclax, 400 mg, orally, QD from Cycle 3 Day 1 until the end of Cycle 12. (1 cycle = 28 days).	Arm B: FCR/BR n=86 Participants Participants received rituximab (375 mg/m\^2 in Cycle 1 and 500 mg/m\^2 in Cycles 2-6), on Day 1 of each cycle, plus fludarabine 25 mg/m\^2 and cyclophosphamide 250 mg/m\^2 on Days 1, 2, and 3 of each cycle as IV infusion up to Cycle 6. Participants alternatively received bendamustine 90 mg/m\^2 on Days 1 and 2 of Cycles 1-6 plus rituximab 375 mg/m\^2 on Day 1 of Cycle 1 and 500 mg/m\^2 on Day 1 of Cycles 2-6. (1 cycle = 28 days).
Best Overall Response (BOR)	93.8 percentage of participants Interval 86.01 to 97.94	90.7 percentage of participants Interval 82.49 to 95.9

SECONDARY outcome

Timeframe: Up to approximately 74 months

EFS was defined as the time between the date of randomization and the date of PD/relapse, death, or the start of a new anti-leukemic therapy. PD was defined as any one of the following: appearance of any new lesion such as enlarged lymph nodes (≥ 1.5 cm); increase by ≥ 50% in greatest diameter of any previous site (≥ 1.5 cm); increase in the spleen/liver size by ≥ 50% or de novo appearance of splenomegaly/hepatomegaly; increase in blood lymphocytes by 50% or more with at least 5x10\^9/L B lymphocytes; transformation to a more aggressive histology; occurrence of cytopenia; posttreatment: progression of any cytopenia, documented by a decrease of Hb ≥ 2 g/dL or 10 g/dL, or by a decrease of platelet counts ≥ 50%/100x10\^9/L, which occurs at least 3 months after treatment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to approximately 74 months

OS was defined as the time between the date of randomization and the date of death due to any cause.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to Cycle 1 Day 22 (1 cycle=28 days)

Population: FAS included all randomized participants, analyzed according to the treatment to which they were randomized.

TLS risk reduction rate in the VEN + G arm was defined as the reduction in the percentage of participants who were TLS high-risk after 3 doses of obinutuzumab compared to the percentage of participants who were TLS high-risk at baseline. Risk for developing TLS were categorised into: Low - All measurable lymph nodes with the LD \< 5 cm and \< 25x10\^9/L absolute lymphocyte count (ALC); Medium - Any measurable lymph node with the LD ≥5 cm but \<10 cm OR ≥25x10\^9/L ALC; High - Any measurable lymph node with the LD ≥10 cm or the presence of both ≥25x10\^9/L ALC and any measurable lymph node with the LD ≥5 cm but \<10 cm. Percentages have been rounded off to the nearest decimal point.

Outcome measures

Outcome measures
Measure	Arm A: VEN+G n=80 Participants Participants received obinutuzumab, 1000 mg, as IV infusion on Days 1 (and 2), 8, and 15 of Cycle 1 and Day 1 of Cycles 2-6. Participants also received venetoclax, with a 5-week ramp-up period (20 mg \[Cycle 1 Days 22-28\], 50 mg \[Cycle 2 Days 1-7\], 100 mg \[Cycle 2 Days 8-14\], 200 mg \[Cycle 2 Days 15-21\], 400 mg \[Cycle 2 Days 22-28\]) administered orally, QD. After the 5-week ramp-up period, participants received venetoclax, 400 mg, orally, QD from Cycle 3 Day 1 until the end of Cycle 12. (1 cycle = 28 days).	Arm B: FCR/BR Participants received rituximab (375 mg/m\^2 in Cycle 1 and 500 mg/m\^2 in Cycles 2-6), on Day 1 of each cycle, plus fludarabine 25 mg/m\^2 and cyclophosphamide 250 mg/m\^2 on Days 1, 2, and 3 of each cycle as IV infusion up to Cycle 6. Participants alternatively received bendamustine 90 mg/m\^2 on Days 1 and 2 of Cycles 1-6 plus rituximab 375 mg/m\^2 on Day 1 of Cycle 1 and 500 mg/m\^2 on Day 1 of Cycles 2-6. (1 cycle = 28 days).
VEN + G: Tumor Lysis Syndrome (TLS) Risk Reduction Rate High-risk at Baseline	23.8 percentage of participants	—
VEN + G: Tumor Lysis Syndrome (TLS) Risk Reduction Rate High-risk at Cycle 1 Day 22	0 percentage of participants	—

SECONDARY outcome

Timeframe: Cycle 1 Days 22-28 up to Cycle 2 Days 1-7 (1 cycle=28 days)

Population: FAS included all randomized participants, analyzed according to the treatment to which they were randomized.

Reduction in mandatory hospitalizations during venetoclax ramp-up in the VEN + G arm participants was defined as the actual number of protocol-mandated hospitalizations for TLS monitoring during venetoclax ramp-up period after 3 doses of obinutuzumab compared to the number of protocol-mandated hospitalizations for TLS monitoring during venetoclax ramp-up expected at baseline. Ramp-up period for venetoclax was defined as period from Cycle 1, Days 22-28, and Cycle 2, Day 1-Day 7 where the 20 mg and 50 mg daily doses of venetoclax, were administered for participants at TLS-high risk requiring mandated hospitalizations (the hospitalizations at 100, 200 and 400 was only needed if the participant had a TLS event at one of the lower doses). Total number of hospitalizations in high-risk TLS participants at baseline (expected to be N=2 hospitalization) was compared with the number of protocol mandated hospitalizations during the first 2 doses of the ramp-up.

Outcome measures

Outcome measures
Measure	Arm A: VEN+G n=80 Participants Participants received obinutuzumab, 1000 mg, as IV infusion on Days 1 (and 2), 8, and 15 of Cycle 1 and Day 1 of Cycles 2-6. Participants also received venetoclax, with a 5-week ramp-up period (20 mg \[Cycle 1 Days 22-28\], 50 mg \[Cycle 2 Days 1-7\], 100 mg \[Cycle 2 Days 8-14\], 200 mg \[Cycle 2 Days 15-21\], 400 mg \[Cycle 2 Days 22-28\]) administered orally, QD. After the 5-week ramp-up period, participants received venetoclax, 400 mg, orally, QD from Cycle 3 Day 1 until the end of Cycle 12. (1 cycle = 28 days).	Arm B: FCR/BR Participants received rituximab (375 mg/m\^2 in Cycle 1 and 500 mg/m\^2 in Cycles 2-6), on Day 1 of each cycle, plus fludarabine 25 mg/m\^2 and cyclophosphamide 250 mg/m\^2 on Days 1, 2, and 3 of each cycle as IV infusion up to Cycle 6. Participants alternatively received bendamustine 90 mg/m\^2 on Days 1 and 2 of Cycles 1-6 plus rituximab 375 mg/m\^2 on Day 1 of Cycle 1 and 500 mg/m\^2 on Day 1 of Cycles 2-6. (1 cycle = 28 days).
VEN + G: Reduction in Mandatory Hospitalizations During Venetoclax Ramp-up	2 number of hospitalizations	—

SECONDARY outcome

Timeframe: From Day 1 until 28 days after the last dose of study drug, or until initiation of another anti-cancer therapy (up to 74 months)

An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE was any AE that meets any of the following criteria: is fatal; is life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to study drug; is a significant medical event in the investigator's judgment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From Day 1 until 28 days after the last dose of study drug, or until initiation of another anti-cancer therapy (up to 74 months)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: VEN + G: Day 1 of Cycle 1-12, Day 28 after treatment completion/early termination (TC/ET), follow up (FU) visits; FCR/BR: Day 1 of Cycle 1-6, Day 28 after TC/ET, end of combination treatment response visit and FU visit (up to 74 months) (1 cycle=28 days)

The EORTC QLQ-C30 consists 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 quality-of-life (GHS/QoL) scale, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The 28 function and symptom items were scored on a 4-point scale that ranged from "not at all" to "very much," and the 2 GHS/QoL items were scored on a 7-point scale that ranged from "very poor" to "excellent." Raw average scale scores were linearly transformed to range 0-100 with higher scores indicating higher response levels (i.e. higher functioning, higher symptom severity).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: VEN + G: Day 1 of Cycle 1-12, Day 28 after TC/ET, FU visits; FCR/BR: Day 1 of Cycle 1-6, Day 28 after TC/ET, end of combination treatment response visit and FU visit (up to approximately 74 months) (1 cycle=28 days)

MDASI-CLL consists of 25 items over 3 scales that assess core cancer \& CLL-related symptom severity, as well as symptom interference that a participant may have experienced in past 24 hours. Participants were asked to rate severity of 13 symptoms called mean core symptom severity (pain, fatigue, nausea, disturbed sleep, distressed, shortness of breath, remembering things, lack of appetite, drowsy, dry mouth, sadness, vomiting \& numbness/tingling), 6 disease-specific symptoms called mean module symptom severity (night sweats, fever \& chills, lymph node swelling, diarrhea, easy bruising/bleeding \& constipation) \& 6 mean interference on life questions (general activity, walking, work, mood, relations with other people \& enjoyment of life) on a scale from 0-10 with 0 indicating that symptom is "not present" or "did not interfere" with participant's activities \& 10 indicating "as bad as you can imagine" or "interfered completely". Lower scores indicated lower symptom severity/interference.

Outcome measures

Outcome data not reported

Adverse Events

Arm A: VEN+G

Serious events: 47 serious events

Other events: 76 other events

Deaths: 3 deaths

Arm B: FCR/BR

Serious events: 42 serious events

Other events: 80 other events

Deaths: 3 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