Trial Outcomes & Findings for A Study to Assess the Effect of Maintenance Treatment With Rituximab Versus No Treatment in Participants With Progressive B-Cell Chronic Lymphocytic Leukemia (CLL) (NCT NCT00718549)

Last Updated: 2018-08-20

Results Overview

PD occurred if any of the following events was observed: appearance of any new lesion, such as enlarged lymph nodes (greater than \[\>\]1.5 centimeters \[cm\]), splenomegaly, hepatomegaly, or other organ infiltrates; an increase of greater than or equal to (\>/=) 50 percent (%) in greatest determined diameter of any previous site; an increase in the previously noted enlargement of the liver or spleen by \>/=50%; an increase in the number of blood lymphocytes by \>/=50% with B-lymphocytes \>/=5000 per microliter (/mcL); transformation to a more aggressive histology; occurrence of cytopenia (neutropenia, anemia, or thrombocytopenia) attributable to CLL.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

128 participants

Primary outcome timeframe

From randomization to PD, Relapse, or death due to any cause (overall approximately 5 years)

Results posted on

2018-08-20

Participant Flow

A total 136 participants were screened, out of which 128 participants were enrolled in this study.

Participant milestones

Participant milestones
Measure	Induction: Rituximab, Cladribine, Cyclophosphamide Participants received rituximab at a dose of 375 milligrams per meter squared (mg/m\^2) as intravenous (IV) infusion on Day 1, cladribine at a dose of 0.12 milligrams per kilogram per day (mg/kg/day) as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 minutes (min) on Days 2-4 in Cycle 1. Then, rituximab at a dose of 500 mg/m\^2 as IV infusion on Day 1, cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 were administered in Cycles 2-6. Each cycle was of 28 days in duration.	Maintenance Arm: Rituximab Participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to maintenance arm received rituximab treatment for 8 cycles. Twelve weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle until disease progression (up to approximately 96 weeks).	Observation Arm: No Intervention Participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to observation arm did not receive any intervention. Participants were assessed every 4-weeks for the first 12 weeks and every 12-weeks afterwards up to 96 weeks.
Induction Phase STARTED	128	0	0
Induction Phase COMPLETED	66	0	0
Induction Phase NOT COMPLETED	62	0	0
Maintenance/ Observation Phase STARTED	0	33	33
Maintenance/ Observation Phase COMPLETED	0	5	3
Maintenance/ Observation Phase NOT COMPLETED	0	28	30

Reasons for withdrawal

Reasons for withdrawal
Measure	Induction: Rituximab, Cladribine, Cyclophosphamide Participants received rituximab at a dose of 375 milligrams per meter squared (mg/m\^2) as intravenous (IV) infusion on Day 1, cladribine at a dose of 0.12 milligrams per kilogram per day (mg/kg/day) as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 minutes (min) on Days 2-4 in Cycle 1. Then, rituximab at a dose of 500 mg/m\^2 as IV infusion on Day 1, cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 were administered in Cycles 2-6. Each cycle was of 28 days in duration.	Maintenance Arm: Rituximab Participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to maintenance arm received rituximab treatment for 8 cycles. Twelve weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle until disease progression (up to approximately 96 weeks).	Observation Arm: No Intervention Participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to observation arm did not receive any intervention. Participants were assessed every 4-weeks for the first 12 weeks and every 12-weeks afterwards up to 96 weeks.
Induction Phase Disease Progression	1	0	0
Induction Phase Eligibility Criteria Violation	2	0	0
Induction Phase Early Termination - No Additional Info	59	0	0
Maintenance/ Observation Phase Early Termination - No Additional Info	0	15	8
Maintenance/ Observation Phase Death	0	1	2
Maintenance/ Observation Phase Lost to Follow-up	0	4	4
Maintenance/ Observation Phase Progression	0	5	14
Maintenance/ Observation Phase Relapse	0	3	2

Baseline Characteristics

A Study to Assess the Effect of Maintenance Treatment With Rituximab Versus No Treatment in Participants With Progressive B-Cell Chronic Lymphocytic Leukemia (CLL)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Induction: Rituximab, Cladribine, Cyclophosphamide n=128 Participants Participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1, cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 in Cycle 1. Then, rituximab at a dose of 500 mg/m\^2 as IV infusion on Day 1, cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 were administered in Cycles 2-6. Each cycle was of 28 days in duration.
Age, Continuous	57.5 years STANDARD_DEVIATION 8.3 • n=93 Participants
Sex: Female, Male Female	44 Participants n=93 Participants
Sex: Female, Male Male	84 Participants n=93 Participants

PRIMARY outcome

Timeframe: From randomization to PD, Relapse, or death due to any cause (overall approximately 5 years)

Population: Intent-to-treat (ITT) population included all participants who received at least one dose of study medication and had at least one post-treatment efficacy measurement available. Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Maintenance Arm: Rituximab n=33 Participants Participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to maintenance arm received rituximab treatment for 8 cycles. Twelve weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle until disease progression (up to approximately 96 weeks).	Observation Arm: No Intervention n=33 Participants Participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to observation arm did not receive any intervention. Participants were assessed every 4-weeks for the first 12 weeks and every 12-weeks afterwards up to 96 weeks.	All Randomized Participants n=66 Participants Participants with PR or CR after induction phase were randomized to observation arm (received no intervention) or to maintenance arm (12 weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle for 8 cycles or until disease progression \[up to approximately 96 weeks\]).
Percentage of Participants With Disease Progression (PD), Relapse, or Death Due to Any Cause Assessed According to the National Cancer Institute (NCI) Revised Guidelines for the Diagnosis and Treatment of Chronic Lymphocytic Leukemia (CLL)	27.3 percentage of participants	54.5 percentage of participants	40.9 percentage of participants

PRIMARY outcome

Timeframe: From randomization to PD, relapse, or death due to any cause (overall approximately 5 years)

Population: ITT population. Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.

PFS was defined as the time from date of randomization to date of PD, relapse, or death due to any cause. Participants alive with no evidence of PD or relapse were censored at date of last clinical examination. PD occurred if any of the following events was observed: appearance of any new lesion, such as enlarged lymph nodes (\>1.5 cm), splenomegaly, hepatomegaly, or other organ infiltrates; an increase of \>/=50% in greatest determined diameter of any previous site; an increase in the previously noted enlargement of the liver or spleen by \>/=50%; an increase in the number of blood lymphocytes by \>/=50% with B-lymphocytes \>/=5000/mcL; transformation to a more aggressive histology; occurrence of cytopenia (neutropenia, anemia, or thrombocytopenia) attributable to CLL.

Outcome measures

Outcome measures
Measure	Maintenance Arm: Rituximab n=33 Participants Participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to maintenance arm received rituximab treatment for 8 cycles. Twelve weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle until disease progression (up to approximately 96 weeks).	Observation Arm: No Intervention n=33 Participants Participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to observation arm did not receive any intervention. Participants were assessed every 4-weeks for the first 12 weeks and every 12-weeks afterwards up to 96 weeks.	All Randomized Participants n=66 Participants Participants with PR or CR after induction phase were randomized to observation arm (received no intervention) or to maintenance arm (12 weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle for 8 cycles or until disease progression \[up to approximately 96 weeks\]).
Progression-Fee Survival (PFS) Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL	NA years Interval 3.0 to Median and Upper Limit could not be calculated due to insufficient number of participants who had an event.	2.1 years Interval 1.9 to Upper Limit could not be calculated due to insufficient number of participants who had an event.	3.1 years Interval 2.2 to Upper Limit could not be calculated due to insufficient number of participants who had an event.

SECONDARY outcome

Timeframe: 8 weeks after the last dose of rituximab during induction treatment (Week 29) and 12 weeks after the end of maintenance treatment or observation phase (Week 129)

Population: ITT population. Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'Number Analyzed' signifies the number of participants evaluable at specified time point.

CR was achieved if participants met all of the following criteria \>/= 2 months after last treatment: no lymphadenopathy (Ly)/ hepatomegaly/ splenomegaly/constitutional symptoms; neutrophils \>1500/mcL, platelets (PL) \>100,000/mcL, hemoglobin (Hb) \>11.0 grams per deciliter (g/dL), bone marrow (BM) sample must be normocellular for age with lymphocytes \<30% of nucleated cells. PR: a reduction in Ly (decrease in lymph node size by \>/=50% compared to pre-treatment state, no increase in any lymph node, no new enlarged lymph node); a reduction of \>/=50% from pre-treatment state in the lymphocytes count, and in enlargement of the spleen or liver; any one of the following: neutrophils \>1500/mcL, PL \>100,000/mcL (or 50% improvement from baseline), Hb \>11.0 g/dL (or 50% improvement from baseline).

Outcome measures

Outcome measures
Measure	Maintenance Arm: Rituximab n=21 Participants Participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to maintenance arm received rituximab treatment for 8 cycles. Twelve weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle until disease progression (up to approximately 96 weeks).	Observation Arm: No Intervention n=18 Participants Participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to observation arm did not receive any intervention. Participants were assessed every 4-weeks for the first 12 weeks and every 12-weeks afterwards up to 96 weeks.	All Randomized Participants n=97 Participants Participants with PR or CR after induction phase were randomized to observation arm (received no intervention) or to maintenance arm (12 weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle for 8 cycles or until disease progression \[up to approximately 96 weeks\]).
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL Week 29	—	—	73.2 percentage of participants Interval 64.9 to 82.1
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL Week 129	90.5 percentage of participants Interval 85.7 to 100.0	72.2 percentage of participants Interval 55.6 to 92.9	82.1 percentage of participants Interval 71.8 to 93.5

SECONDARY outcome

Timeframe: 8 weeks after the last dose of rituximab during induction treatment (Week 29) and 12 weeks after the end of maintenance treatment or observation phase (Week 129)

MRD was defined by the presence of tumor cells in bone marrow, using 4-color flow cytometry of cluster of differentiation (CD)19/CD5/CD20/CD79b. MRD was assessed in participants who achieved CR or PR. CR: if participants met all of the following criteria \>/=2 months after last treatment: no Ly/ hepatomegaly/ splenomegaly/constitutional symptoms; neutrophils \>1500/mcL, PL \>100,000/mcL, Hb \>11.0 g/dL, BM sample must be normocellular for age with lymphocytes \<30% of nucleated cells. PR: a reduction in Ly; a reduction of \>/=50% from pre-treatment state in the lymphocytes count, and in enlargement of the spleen or liver; any one of the following: neutrophils \>1500/mcL, PL \>100,000/mcL (or 50% improvement from baseline), Hb \>11.0 g/dL (or 50% improvement from baseline).

Outcome measures

Outcome measures
Measure	Maintenance Arm: Rituximab n=14 Participants Participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to maintenance arm received rituximab treatment for 8 cycles. Twelve weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle until disease progression (up to approximately 96 weeks).	Observation Arm: No Intervention n=10 Participants Participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to observation arm did not receive any intervention. Participants were assessed every 4-weeks for the first 12 weeks and every 12-weeks afterwards up to 96 weeks.	All Randomized Participants n=65 Participants Participants with PR or CR after induction phase were randomized to observation arm (received no intervention) or to maintenance arm (12 weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle for 8 cycles or until disease progression \[up to approximately 96 weeks\]).
Percentage of Participants With Minimal Residual Disease (MRD) According to Rawstron Criteria in Participants With CR or PR Week 29	—	—	15.4 percentage of participants Interval 7.7 to 23.7
Percentage of Participants With Minimal Residual Disease (MRD) According to Rawstron Criteria in Participants With CR or PR Week 129	28.6 percentage of participants Interval 14.3 to 55.6	20.0 percentage of participants Interval 10.0 to 48.7	25.0 percentage of participants Interval 12.5 to 43.9

SECONDARY outcome

Timeframe: From randomization to PD, relapse, or death due to any cause (overall approximately 5 years)

Population: ITT population. Overall Number of Participants Analyzed: participants evaluable for this outcome; Number Analyzed: participants evaluable for specified category. This outcome was planned to be reported for groups defined by clinical and biochemical factors (i.e. reported categories) among All Randomized Participants only.

PFS: time from date of randomization to date of PD, relapse, or death from any cause. Participants alive with no evidence of PD or relapse were censored at date of last clinical examination. PD: appearance of any new lesion, such as enlarged lymph nodes (\>1.5 cm), splenomegaly, hepatomegaly, or other organ infiltrates; an increase of \>/=50% in greatest determined diameter of any previous site; an increase in previously noted enlargement of liver or spleen by \>/=50%; an increase in number of blood lymphocytes by \>/=50% with B-lymphocytes \>/=5000/mcL; transformation to a more aggressive histology; or occurrence of cytopenia attributable to CLL. Rai Stage: staging for CLL, based on lymphocyte, red blood cell and platelet counts and size of lymph nodes, spleen, and liver. Rai Stage I or II are intermediate risk CLL and Rai Stage III or IV are high risk CLL. This outcome measure assessed relationship between clinical markers and clinical outcome (PFS) after study treatment.

Outcome measures

Outcome measures
Measure	Maintenance Arm: Rituximab n=66 Participants Participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to maintenance arm received rituximab treatment for 8 cycles. Twelve weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle until disease progression (up to approximately 96 weeks).	Observation Arm: No Intervention Participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to observation arm did not receive any intervention. Participants were assessed every 4-weeks for the first 12 weeks and every 12-weeks afterwards up to 96 weeks.	All Randomized Participants Participants with PR or CR after induction phase were randomized to observation arm (received no intervention) or to maintenance arm (12 weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle for 8 cycles or until disease progression \[up to approximately 96 weeks\]).
PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors Age <60 years	3.0 years Interval 2.2 to Upper Limit could not be calculated due to insufficient number of participants who had an event.	—	—
PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors Age >/=60 years	4.0 years Interval 1.9 to Upper Limit could not be calculated due to insufficient number of participants who had an event.	—	—
PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors Sex: Female	4.0 years Interval 2.2 to Upper Limit could not be calculated due to insufficient number of participants who had an event.	—	—
PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors Sex: Male	3.0 years Interval 2.1 to Upper Limit could not be calculated due to insufficient number of participants who had an event.	—	—
PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors Rai Stage: I or II	3.1 years Interval 2.1 to Upper Limit could not be calculated due to insufficient number of participants who had an event.	—	—
PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors Rai Stage: III or IV	3.0 years Interval 2.1 to Upper Limit could not be calculated due to insufficient number of participants who had an event.	—	—
PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors Beta-2-Microglobulin >/= Median Value	1.9 years Interval 1.4 to Upper Limit could not be calculated due to insufficient number of participants who had an event.	—	—
PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors Beta-2-Microglobulin <Median Value	NA years Interval 3.5 to Median and Upper Limit could not be calculated due to insufficient number of participants who had an event.	—	—
PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors Zeta-Associated Protein (ZAP)-70: Negative	3.0 years Interval 2.1 to Upper Limit could not be calculated due to insufficient number of participants who had an event.	—	—
PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors ZAP-70 Expression: Positive	NA years Interval 4.0 to Median and Upper Limit could not be calculated due to insufficient number of participants who had an event.	—	—
PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors CD38 Expression: Negative	2.1 years Interval 1.9 to Upper Limit could not be calculated due to insufficient number of participants who had an event.	—	—
PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors CD38 Expression: Positive	2.8 years Interval 1.9 to Upper Limit could not be calculated due to insufficient number of participants who had an event.	—	—
PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors Cytogenetic abnormality 17p: No	3.1 years Interval 2.2 to Upper Limit could not be calculated due to insufficient number of participants who had an event.	—	—
PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors Cytogenetic abnormality 17p: Yes	1.9 years Interval 1.9 to Upper Limit could not be calculated due to insufficient number of participants who had an event.	—	—
PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors Cytogenetic abnormality 13q: No	3.5 years Interval 1.4 to Upper Limit could not be calculated due to insufficient number of participants who had an event.	—	—
PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors Cytogenetic abnormality 13q: Yes	3.0 years Interval 1.9 to Upper Limit could not be calculated due to insufficient number of participants who had an event.	—	—
PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors Cytogenetic abnormality 11q: No	3.5 years Interval 2.1 to Upper Limit could not be calculated due to insufficient number of participants who had an event.	—	—
PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors Cytogenetic abnormality 11q: Yes	2.8 years Interval 1.9 to Upper Limit could not be calculated due to insufficient number of participants who had an event.	—	—
PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors Cytogenetic abnormality 12q: No	2.2 years Interval 1.9 to Upper Limit could not be calculated due to insufficient number of participants who had an event.	—	—
PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors Cytogenetic abnormality 12q: Yes	3.1 years Interval 3.1 to Upper Limit could not be calculated due to insufficient number of participants who had an event.	—	—

SECONDARY outcome

Timeframe: 8 weeks after the last dose of rituximab during induction treatment (Week 29)

Population: ITT population. Number Analyzed: participants evaluable for specified category. This outcome was planned to be reported for groups defined by clinical and biochemical factors (i.e. reported categories) among Participants included in Overall IIT population only.

CR was achieved if participants met all of the following criteria \>/= 2 months after last treatment: no Ly/ hepatomegaly/ splenomegaly/constitutional symptoms; neutrophils \>1500/mcL, PL \>100,000/mcL, Hb \>11.0 g/dL, BM sample must be normocellular for age with lymphocytes \<30% of nucleated cells. PR: a reduction in Ly; a reduction of \>/=50% from pre-treatment state in the lymphocytes count, and in enlargement of the spleen or liver; any one of the following: neutrophils \>1500/mcL, PL \>100,000/mcL (or 50% improvement from baseline), Hb \>11.0 g/dL (or 50% improvement from baseline). Rai Stage: staging for CLL, based on lymphocyte, red blood cell and platelet counts and size of lymph nodes, spleen, and liver. Rai Stage I or II are intermediate risk CLL and Rai Stage III or IV are high risk CLL. This outcome measure assessed the relationship between clinical markers and clinical outcome (response) after study treatment.

Outcome measures

Outcome measures
Measure	Maintenance Arm: Rituximab n=97 Participants Participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to maintenance arm received rituximab treatment for 8 cycles. Twelve weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle until disease progression (up to approximately 96 weeks).	Observation Arm: No Intervention Participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to observation arm did not receive any intervention. Participants were assessed every 4-weeks for the first 12 weeks and every 12-weeks afterwards up to 96 weeks.	All Randomized Participants Participants with PR or CR after induction phase were randomized to observation arm (received no intervention) or to maintenance arm (12 weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle for 8 cycles or until disease progression \[up to approximately 96 weeks\]).
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 29 Age <60 years	73.3 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 29 Age >/=60 years	73.0 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 29 Sex: Female	80.6 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 29 Sex: Male	69.7 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 29 Rai Stage: I or II	77.5 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 29 Rai Stage: III or IV	61.5 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 29 Beta-2-Microglobulin >/= Median Value	64.6 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 29 Beta-2-Microglobulin <Median Value	83.0 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 29 ZAP-70 Expression: Negative	67.1 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 29 ZAP-70 Expression: Positive	94.7 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 29 CD38 Expression: Negative	73.1 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 29 CD38 Expression: Positive	71.4 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 29 Cytogenetic abnormality 17p: No	72.8 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 29 Cytogenetic abnormality 17p: Yes	71.4 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 29 Cytogenetic abnormality 13q: No	62.9 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 29 Cytogenetic abnormality 13q: Yes	76.1 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 29 Cytogenetic abnormality 11q: No	69.5 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 29 Cytogenetic abnormality 11q: Yes	79.2 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 29 Cytogenetic abnormality 12q: No	67.6 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 29 Cytogenetic abnormality 12q: Yes	66.7 percentage of participants	—	—

SECONDARY outcome

Timeframe: 12 weeks after the end of maintenance treatment or observation phase (Week 129)

CR was achieved if participants met all of the following criteria \>/=2 months after last treatment: no Ly/ hepatomegaly/ splenomegaly/constitutional symptoms; neutrophils \>1500/mcL, PL \>100,000/mcL, Hb \>11.0 g/dL, BM sample must be normocellular for age with lymphocytes \<30% of nucleated cells. PR: a reduction in Ly; a reduction of \>/=50% from pre-treatment state in the lymphocytes count, and in enlargement of the spleen or liver; any one of the following: neutrophils \>1500/mcL, PL \>100,000/mcL (or 50% improvement from baseline), Hb \>11.0 g/dL (or 50% improvement from baseline). Rai Stage: staging for CLL, based on lymphocyte, red blood cell and platelet counts and size of lymph nodes, spleen, and liver. Rai Stage I or II are intermediate risk CLL and Rai Stage III or IV are high risk CLL. This outcome measure assessed the relationship between clinical markers and clinical outcome (response) after study treatment.

Outcome measures

Outcome measures
Measure	Maintenance Arm: Rituximab n=39 Participants Participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to maintenance arm received rituximab treatment for 8 cycles. Twelve weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle until disease progression (up to approximately 96 weeks).	Observation Arm: No Intervention Participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to observation arm did not receive any intervention. Participants were assessed every 4-weeks for the first 12 weeks and every 12-weeks afterwards up to 96 weeks.	All Randomized Participants Participants with PR or CR after induction phase were randomized to observation arm (received no intervention) or to maintenance arm (12 weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle for 8 cycles or until disease progression \[up to approximately 96 weeks\]).
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 129 Age <60 years	80.8 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 129 Age >/=60 years	84.6 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 129 Sex: Female	85.7 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 129 Sex: Male	80.0 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 129 Rai Stage: I or II	80.6 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 129 Rai Stage: III or IV	87.5 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 129 Beta-2-Microglobulin >/= Median Value	76.9 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 129 Beta-2-Microglobulin <Median Value	84.0 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 129 ZAP-70 Expression: Negative	83.3 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 129 ZAP-70 Expression: Positive	83.3 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 129 CD38 Expression: Negative	77.8 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 129 CD38 Expression: Positive	75.0 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 129 Cytogenetic abnormality 17p: No	86.7 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 129 Cytogenetic abnormality 17p: Yes	50.0 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 129 Cytogenetic abnormality 13q: No	90.0 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 129 Cytogenetic abnormality 13q: Yes	76.5 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 129 Cytogenetic abnormality 11q: No	84.2 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 129 Cytogenetic abnormality 11q: Yes	80.0 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 129 Cytogenetic abnormality 12q: No	76.2 percentage of participants	—	—
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 129 Cytogenetic abnormality 12q: Yes	100.0 percentage of participants	—	—

SECONDARY outcome

Timeframe: 8 weeks after the last dose of rituximab during induction treatment (Week 29)

MRD: the presence of tumor cells in bone marrow, using 4-color flow cytometry of CD19/CD5/CD20/CD79b. MRD was assessed in participants who achieved CR or PR. CR (\>/=2 months after last treatment): no Ly/ hepatomegaly/ splenomegaly/constitutional symptoms; neutrophils \>1500/mcL, PL \>100,000/mcL, Hb \>11.0 g/dL, BM sample must be normocellular for age with lymphocytes \<30% of nucleated cells. PR: a reduction in Ly; a reduction of \>/=50% from pre-treatment state in the lymphocytes count, and in enlargement of the spleen or liver; any one of the following: neutrophils \>1500/mcL, PL \>100,000/mcL (or 50% improvement from baseline), Hb \>11.0 g/dL (or 50% improvement from baseline). Rai Stage: staging for CLL, based on lymphocyte, red blood cell and platelet counts and size of lymph nodes, spleen, and liver. Rai Stage I or II are intermediate risk CLL and Rai Stage III or IV are high risk CLL. This outcome measure assessed relationship between clinical markers and MRD after study treatment.

Outcome measures

Outcome measures
Measure	Maintenance Arm: Rituximab n=65 Participants Participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to maintenance arm received rituximab treatment for 8 cycles. Twelve weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle until disease progression (up to approximately 96 weeks).	Observation Arm: No Intervention Participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to observation arm did not receive any intervention. Participants were assessed every 4-weeks for the first 12 weeks and every 12-weeks afterwards up to 96 weeks.	All Randomized Participants Participants with PR or CR after induction phase were randomized to observation arm (received no intervention) or to maintenance arm (12 weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle for 8 cycles or until disease progression \[up to approximately 96 weeks\]).
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 Age <60 years	87.8 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 Age >/=60 years	79.2 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 Sex: Female	87.5 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 Sex: Male	82.9 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 Rai Stage: I or II	80.4 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 Rai Stage: III or IV	100.0 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 Beta-2-Microglobulin >/= Median Value	93.1 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 Beta-2-Microglobulin <Median Value	77.1 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 ZAP-70 Expression: Negative	82.6 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 ZAP-70 Expression: Positive	100.0 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 CD38 Expression: Negative	83.3 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 CD38 Expression: Positive	95.5 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 Cytogenetic abnormality 17p: No	83.6 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 Cytogenetic abnormality 17p: Yes	100.0 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 Cytogenetic abnormality 13q: No	84.2 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 Cytogenetic abnormality 13q: Yes	81.8 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 Cytogenetic abnormality 11q: No	83.3 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 Cytogenetic abnormality 11q: Yes	84.2 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 Cytogenetic abnormality 12q: No	80.5 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 Cytogenetic abnormality 12q: Yes	75.0 percentage of participants	—	—

SECONDARY outcome

Timeframe: 12 weeks after the end of maintenance treatment or observation phase (Week 129)

Outcome measures

Outcome measures
Measure	Maintenance Arm: Rituximab n=24 Participants Participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to maintenance arm received rituximab treatment for 8 cycles. Twelve weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle until disease progression (up to approximately 96 weeks).	Observation Arm: No Intervention Participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to observation arm did not receive any intervention. Participants were assessed every 4-weeks for the first 12 weeks and every 12-weeks afterwards up to 96 weeks.	All Randomized Participants Participants with PR or CR after induction phase were randomized to observation arm (received no intervention) or to maintenance arm (12 weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle for 8 cycles or until disease progression \[up to approximately 96 weeks\]).
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 Age <60 years	72.2 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 Age >/=60 years	83.3 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 Sex: Female	71.4 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 Sex: Male	76.5 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 Rai Stage: I or II	75.0 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 Rai Stage: III or IV	75.0 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 Beta-2-Microglobulin >/= Median Value	88.9 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 Beta-2-Microglobulin <Median Value	71.4 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 ZAP-70 Expression: Negative	66.7 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 ZAP-70 Expression: Positive	100.0 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 CD38 Expression: Negative	60.0 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 CD38 Expression: Positive	77.8 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 Cytogenetic abnormality 17p: No	76.2 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 Cytogenetic abnormality 17p: Yes	0.0 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 Cytogenetic abnormality 13q: No	75.0 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 Cytogenetic abnormality 13q: Yes	66.7 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 Cytogenetic abnormality 11q: No	66.7 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 Cytogenetic abnormality 11q: Yes	75.0 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 Cytogenetic abnormality 12q: No	66.7 percentage of participants	—	—
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 Cytogenetic abnormality 12q: Yes	66.7 percentage of participants	—	—

Adverse Events

Induction (Excluding Maintenance/ Observation)

Serious events: 23 serious events

Other events: 58 other events

Deaths: 0 deaths

Maintenance Arm: Rituximab

Serious events: 13 serious events

Other events: 31 other events

Deaths: 0 deaths

Observation Arm: No Intervention

Serious events: 9 serious events

Other events: 32 other events

Deaths: 0 deaths

All Participants

Serious events: 45 serious events

Other events: 121 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