Trial Outcomes & Findings for Lenalidomide Plus Rituximab Followed by Lenalidomide Versus Rituximab Maintenance for Relapsed/Refractory Follicular, Marginal Zone or Mantle Cell Lymphoma. (NCT NCT01996865)

NCT ID: NCT01996865

Last Updated: 2025-07-10

Results Overview

Progression free survival (PFS) is defined as the time from the date of first dose of maintenance therapy to the date of the first objective documentation of tumor progression or death due to any cause. Analysis was based on Kaplan Meier estimates. The PFS events were determined using a modification of the IWG 1999 criteria.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

503 participants

Primary outcome timeframe

From the first dose date of maintenance therapy to objective disease progression or death from any cause, whichever occurs first (up to approximately 432 weeks)

Results posted on

2025-07-10

Participant Flow

503 participants joined this study. All participants started in the induction period; only those who did not progress after 12 cycles of treatment were randomized to receive treatment in the maintenance period.

Participant milestones

Participant milestones
Measure	Induction Period: Lenalidomide + Rituximab Induction Period (12 cycles): participants received lenalidomide 20 mg (10 mg if creatinine clearance ≥ 30 mL/min but \< 60 mL/min) once daily on Days 1 to 21 of every 28-day Cycle for Cycles 1 to 12 AND rituximab 375 mg/m2 every week in Cycle 1 (Days 1, 8, 15, and 22) and Day 1 of every 28-day Cycle for Cycles 3, 5, 7, 9, and 11	Arm A: Lenalidomide + Rituximab Maintenance Period (18 Cycles): lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle for Cycles 13 to 30 AND rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29. Followed by Optional Maintenance Period (up to PD): Lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle up to PD. This treatment will be at the discretion of the participant and the investigator.	Arm B: Rituximab Maintenance Period (18 Cycles): participants received rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29
Induction Period STARTED	503	0	0
Induction Period Treated	500	0	0
Induction Period COMPLETED	284	0	0
Induction Period NOT COMPLETED	219	0	0
Maintenance Period STARTED	0	135	132
Maintenance Period Treated	0	134	132
Maintenance Period COMPLETED	0	78	89
Maintenance Period NOT COMPLETED	0	57	43

Reasons for withdrawal

Reasons for withdrawal
Measure	Induction Period: Lenalidomide + Rituximab Induction Period (12 cycles): participants received lenalidomide 20 mg (10 mg if creatinine clearance ≥ 30 mL/min but \< 60 mL/min) once daily on Days 1 to 21 of every 28-day Cycle for Cycles 1 to 12 AND rituximab 375 mg/m2 every week in Cycle 1 (Days 1, 8, 15, and 22) and Day 1 of every 28-day Cycle for Cycles 3, 5, 7, 9, and 11	Arm A: Lenalidomide + Rituximab Maintenance Period (18 Cycles): lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle for Cycles 13 to 30 AND rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29. Followed by Optional Maintenance Period (up to PD): Lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle up to PD. This treatment will be at the discretion of the participant and the investigator.	Arm B: Rituximab Maintenance Period (18 Cycles): participants received rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29
Induction Period Protocol Violation	1	0	0
Induction Period Progressive Disease	4	0	0
Induction Period Lost to Follow-up	10	0	0
Induction Period Other Reasons	13	0	0
Induction Period Adverse Event	20	0	0
Induction Period Withdrawal by Subject	60	0	0
Induction Period Death	111	0	0
Maintenance Period Protocol Violation	0	1	1
Maintenance Period Other reasons	0	8	5
Maintenance Period Progressive Disease	0	6	23
Maintenance Period Withdrawal by Subject	0	18	4
Maintenance Period Adverse Event	0	7	7
Maintenance Period Death	0	15	3
Maintenance Period Lost to Follow-up	0	2	0

Baseline Characteristics

Lenalidomide Plus Rituximab Followed by Lenalidomide Versus Rituximab Maintenance for Relapsed/Refractory Follicular, Marginal Zone or Mantle Cell Lymphoma.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Overall Study n=503 Participants All participants who were enrolled into the study.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	209 Participants n=5 Participants
Age, Categorical >=65 years	294 Participants n=5 Participants
Sex: Female, Male Female	215 Participants n=5 Participants
Sex: Female, Male Male	288 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	33 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	463 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	7 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	17 Participants n=5 Participants
Race (NIH/OMB) White	468 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the first dose date of maintenance therapy to objective disease progression or death from any cause, whichever occurs first (up to approximately 432 weeks)

Population: All randomized participants in Arm A and Arm B, as prespecified in the protocol

Outcome measures

Outcome measures
Measure	Arm A: Lenalidomide + Rituximab n=135 Participants Maintenance Period (18 Cycles): lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle for Cycles 13 to 30 AND rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29. Followed by Optional Maintenance Period (up to PD): Lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle up to PD. This treatment will be at the discretion of the participant and the investigator.	Arm B: Rituximab n=132 Participants Maintenance Period (18 Cycles): participants received rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29	Arm B: Rituximab Maintenance Period (18 Cycles): participants received rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29
Progression Free Survival (PFS)	263.1 Weeks Interval 166.1 to Upper limit not calculated due to insufficient number of events.	229.1 Weeks Interval 173.7 to Upper limit not calculated due to insufficient number of events.	—

SECONDARY outcome

Timeframe: From the first dose date of maintenance therapy to death from any cause (up to approximately 480 weeks)

Population: All randomized participants in Arm A and Arm B, as prespecified in the protocol

Overall Survival (OS) is defined as the time between the first dose date of maintenance therapy and death from any cause. Participants who complete the study and are still alive at the time of the clinical data cutoff date will be censored at the last visit date or the last contact date, whichever is later. Participants who were lost to follow-up prior to the clinical data cut-off date will also be censored at the time of the last contact. Analysis was based on Kaplan Meier estimates and Hazard Ratio (HR).

Outcome measures

Outcome measures
Measure	Arm A: Lenalidomide + Rituximab n=135 Participants Maintenance Period (18 Cycles): lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle for Cycles 13 to 30 AND rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29. Followed by Optional Maintenance Period (up to PD): Lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle up to PD. This treatment will be at the discretion of the participant and the investigator.	Arm B: Rituximab n=132 Participants Maintenance Period (18 Cycles): participants received rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29	Arm B: Rituximab Maintenance Period (18 Cycles): participants received rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29
Overall Survival (OS)	NA Weeks Interval 439.4 to Median and upper limit not calculated due to insufficient number of events.	NA Weeks Interval 395.7 to Median and upper limit not calculated due to insufficient number of events.	—

SECONDARY outcome

Timeframe: From the first dose date of maintenance therapy to death from any cause (up to approximately 432 weeks)

Population: All randomized participants in Arm A and Arm B, as prespecified in the protocol

Improvement of Response (IOR) is the percentage of participants with improved tumor response during the maintenance phase (converted from partial response at end of induction to complete response or complete response unconfirmed as best response) and participants who converted from stable disease at the end of induction period to partial response or better as best response during maintenance phase.

Outcome measures

Outcome measures
Measure	Arm A: Lenalidomide + Rituximab n=135 Participants Maintenance Period (18 Cycles): lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle for Cycles 13 to 30 AND rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29. Followed by Optional Maintenance Period (up to PD): Lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle up to PD. This treatment will be at the discretion of the participant and the investigator.	Arm B: Rituximab n=132 Participants Maintenance Period (18 Cycles): participants received rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29	Arm B: Rituximab Maintenance Period (18 Cycles): participants received rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29
Improvement of Response (IOR)	20 Percentage of participants Interval 13.6 to 27.7	11.4 Percentage of participants Interval 6.5 to 18.0	—

SECONDARY outcome

Timeframe: From the first dose date of maintenance therapy up to CR, CRu, PR, or treatment change (up to approximately 432 weeks)

Population: All randomized participants in Arm A and Arm B, as prespecified in the protocol

The overall response rate (ORR) is defined as the percentage of participants with a best response of at least partial response (including complete response, complete response unconfirmed and partial response) after the first dose date of maintenance therapy and prior to any treatment change.

Outcome measures

Outcome measures
Measure	Arm A: Lenalidomide + Rituximab n=115 Participants Maintenance Period (18 Cycles): lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle for Cycles 13 to 30 AND rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29. Followed by Optional Maintenance Period (up to PD): Lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle up to PD. This treatment will be at the discretion of the participant and the investigator.	Arm B: Rituximab n=105 Participants Maintenance Period (18 Cycles): participants received rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29	Arm B: Rituximab Maintenance Period (18 Cycles): participants received rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29
Overall Response Rate (ORR)	85.2 Percentage of participants Interval 78.1 to 90.7	79.5 Percentage of participants Interval 71.7 to 86.1	—

SECONDARY outcome

Timeframe: From the first dose date of maintenance therapy up to CR or CRu (up to approximately 432 weeks)

Population: All randomized participants in Arm A and Arm B, as prespecified in the protocol

Best Complete Response Rate (CRR), defined as the proportion of participants with a best response of at least CRu (including CR and CRu) after the first dose date of maintenance therapy and prior to any treatment change.

Outcome measures

Outcome measures
Measure	Arm A: Lenalidomide + Rituximab n=135 Participants Maintenance Period (18 Cycles): lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle for Cycles 13 to 30 AND rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29. Followed by Optional Maintenance Period (up to PD): Lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle up to PD. This treatment will be at the discretion of the participant and the investigator.	Arm B: Rituximab n=132 Participants Maintenance Period (18 Cycles): participants received rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29	Arm B: Rituximab Maintenance Period (18 Cycles): participants received rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29
Complete Response Rate (CRR)	60.7 Percentage of participants Interval 52.0 to 69.0	58.3 Percentage of participants Interval 49.4 to 66.8	—

SECONDARY outcome

Timeframe: From the initial response (at least PR) after the first dose date of maintenance therapy and prior to treatment change to documented disease progression or death, whichever occurs first (up to approximately 432 weeks)

Population: The analysis is only performed for participants who have achieved PR or better after the first dose date of maintenance therapy and prior to any treatment change. Arm B includes 3 additional participants who achieved CR/CRu/PR in the follow-up period.

DOR is from initial response (at least CRu) after the first dose date of maintenance therapy and prior to treatment change to documented disease progression or death. Participants who have not progressed or died at the time of the clinical data cutoff date will be censored at the last assessment showing no progression. Participants who change treatment without evidence of disease progression will be censored at the last assessment showing no progression prior to treatment change. Analysis was based on Kaplan Meier estimates.

Outcome measures

Outcome measures
Measure	Arm A: Lenalidomide + Rituximab n=115 Participants Maintenance Period (18 Cycles): lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle for Cycles 13 to 30 AND rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29. Followed by Optional Maintenance Period (up to PD): Lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle up to PD. This treatment will be at the discretion of the participant and the investigator.	Arm B: Rituximab n=108 Participants Maintenance Period (18 Cycles): participants received rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29	Arm B: Rituximab Maintenance Period (18 Cycles): participants received rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29
Duration of Response (DOR)	268.3 Weeks Interval 168.0 to Upper limit not calculated due to insufficient number of events	306.0 Weeks Interval 183.7 to Upper limit not calculated due to insufficient number of events	—

SECONDARY outcome

Timeframe: From the first dose date of maintenance therapy to the time of first documented administration of new anti-lymphoma therapy (up to approximately 300 weeks)

Population: All randomized participants in Arm A and Arm B, as prespecified in the protocol

Time to next anti-lymphoma treatment is defined as the time from the first dose date of maintenance therapy to the time of first documented administration of new anti-lymphoma therapy. Participants without new treatment therapy will be censored at the last visit. Analysis was based on Kaplan Meier estimates.

Outcome measures

Outcome measures
Measure	Arm A: Lenalidomide + Rituximab n=135 Participants Maintenance Period (18 Cycles): lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle for Cycles 13 to 30 AND rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29. Followed by Optional Maintenance Period (up to PD): Lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle up to PD. This treatment will be at the discretion of the participant and the investigator.	Arm B: Rituximab n=132 Participants Maintenance Period (18 Cycles): participants received rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29	Arm B: Rituximab Maintenance Period (18 Cycles): participants received rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29
Time to Next Anti-lymphoma Treatment	NA Weeks Interval 300.4 to Median and upper limit not calculated due to insufficient number of events	NA Weeks Interval 283.4 to Median and upper limit not calculated due to insufficient number of events	—

SECONDARY outcome

Timeframe: From the first dose date of maintenance therapy to the time of histological transformation (up to approximately 432 weeks)

Population: All randomized participants in Arm A and Arm B without transformed Follicular Lymphoma (tFL)

Time to histological transformation is defined as from the first dose date of maintenance therapy to the time of histological transformation as measured based on documentation of histological transformation (as assessed by the investigator). Analysis was based on Kaplan Meier estimates. In case of clinical suspicion of transformation, including rapid disease progression, unexpected changes in "B" symptoms or rapidly increasing LDH, a biopsy should be performed. In this clinical trial, histological transformation will be considered disease progression. This endpoint will not be calculated for participants randomized with transformed Follicular Lymphoma (tFL).

Outcome measures

Outcome measures
Measure	Arm A: Lenalidomide + Rituximab n=133 Participants Maintenance Period (18 Cycles): lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle for Cycles 13 to 30 AND rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29. Followed by Optional Maintenance Period (up to PD): Lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle up to PD. This treatment will be at the discretion of the participant and the investigator.	Arm B: Rituximab n=129 Participants Maintenance Period (18 Cycles): participants received rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29	Arm B: Rituximab Maintenance Period (18 Cycles): participants received rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29
Time to Histological Transformation	NA Weeks Median, lower and upper limit not calculated due to insufficient number of events.	NA Weeks Median, lower and upper limit not calculated due to insufficient number of events.	—

SECONDARY outcome

Timeframe: From the initial CR/CRu after the first dose date of maintenance therapy and prior to treatment change to documented disease progression or death, whichever occurs first (up to approximately 432 weeks)

Population: The analysis is only performed for participants who have achieved CR or CRu after the first dose date of maintenance therapy and prior to any treatment change.

Duration of complete response (DOCR) is calculated as the time from the initial response (CR or CRu) after the first dose date of maintenance therapy and prior to treatment change to documented disease progression or death. Analysis was based on Kaplan Meier estimates. Participants who have not progressed or died at the time of the clinical data cutoff date will be censored at the last assessment showing no progression. Participants who change treatment without evidence of disease progression will be censored at the last assessment showing no progression prior to treatment change.

Outcome measures

Outcome measures
Measure	Arm A: Lenalidomide + Rituximab n=85 Participants Maintenance Period (18 Cycles): lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle for Cycles 13 to 30 AND rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29. Followed by Optional Maintenance Period (up to PD): Lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle up to PD. This treatment will be at the discretion of the participant and the investigator.	Arm B: Rituximab n=82 Participants Maintenance Period (18 Cycles): participants received rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29	Arm B: Rituximab Maintenance Period (18 Cycles): participants received rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29
Duration of Complete Response (DOCR)	298.0 Weeks Interval 176.0 to Upper limit not calculated due to insufficient number of events	NA Weeks Interval 221.1 to Median and upper limit not calculated due to insufficient number of events	—

SECONDARY outcome

Timeframe: From first dose up to 30 days after last dose (up to approximately 64 weeks for induction period and 427 weeks for maintenance period)

Population: All treated participants

Number of participants experiencing AEs, SAEs, AEs leading to study discontinuation, and AEs of interest (AEIs). An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. SAEs is any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization; results significant disability; or is a congenital anomaly/birth defect. TEAEs are defined as AEs with an onset date on or after the first dose of study treatment up to 30 days after the last dose of study treatment in the study, or if a pre-existing condition worsens in severity or becomes serious after receiving the first dose of study treatment.

Outcome measures

Outcome measures
Measure	Arm A: Lenalidomide + Rituximab n=500 Participants Maintenance Period (18 Cycles): lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle for Cycles 13 to 30 AND rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29. Followed by Optional Maintenance Period (up to PD): Lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle up to PD. This treatment will be at the discretion of the participant and the investigator.	Arm B: Rituximab n=134 Participants Maintenance Period (18 Cycles): participants received rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29	Arm B: Rituximab n=132 Participants Maintenance Period (18 Cycles): participants received rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29
Participants Experiencing Treatment Emergent Adverse Events (TEAEs) Participants experiencing at least one TEAE	499 Participants	133 Participants	120 Participants
Participants Experiencing Treatment Emergent Adverse Events (TEAEs) Participants experiencing at least one serious TEAE	172 Participants	57 Participants	22 Participants

SECONDARY outcome

Timeframe: From first dose up to 30 days after last dose (up to approximately 64 weeks for induction period and 427 weeks for maintenance period)

Population: All treated participants

The number of participants who experienced adverse events related to vital sign measurements

Outcome measures

Outcome measures
Measure	Arm A: Lenalidomide + Rituximab n=500 Participants Maintenance Period (18 Cycles): lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle for Cycles 13 to 30 AND rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29. Followed by Optional Maintenance Period (up to PD): Lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle up to PD. This treatment will be at the discretion of the participant and the investigator.	Arm B: Rituximab n=134 Participants Maintenance Period (18 Cycles): participants received rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29	Arm B: Rituximab n=132 Participants Maintenance Period (18 Cycles): participants received rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29
Participants Experiencing Adverse Events Related to Vital Signs Hypertension	34 Participants	9 Participants	6 Participants
Participants Experiencing Adverse Events Related to Vital Signs Hypotension	22 Participants	4 Participants	5 Participants
Participants Experiencing Adverse Events Related to Vital Signs Hypoxia	5 Participants	2 Participants	0 Participants

SECONDARY outcome

Timeframe: From first dose up to 30 days after last dose (up to approximately 64 weeks for induction period and 427 weeks for maintenance period)

Population: All treated participants

Clinical laboratory values in induction period include any laboratory values that are taken after the first dose date of induction therapy through 28 days after the last dose date of induction therapy or before the first dose date of maintenance therapy, whichever is earlier. Graded according to the NCI CTCAE version 4.03, except for tumor flare reaction, which is accessed using NCI CTCAE version 3.0. Participants with zero maximum grade are excluded.

Outcome measures

Outcome measures
Measure	Arm A: Lenalidomide + Rituximab n=500 Participants Maintenance Period (18 Cycles): lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle for Cycles 13 to 30 AND rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29. Followed by Optional Maintenance Period (up to PD): Lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle up to PD. This treatment will be at the discretion of the participant and the investigator.	Arm B: Rituximab n=134 Participants Maintenance Period (18 Cycles): participants received rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29	Arm B: Rituximab n=132 Participants Maintenance Period (18 Cycles): participants received rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29
Participants With Grade 3 or Grade 4 Hematology Parameters Anemia - Grade 3	31 Participants	7 Participants	0 Participants
Participants With Grade 3 or Grade 4 Hematology Parameters Leukopenia - Grade 3	101 Participants	19 Participants	6 Participants
Participants With Grade 3 or Grade 4 Hematology Parameters Thrombocytopenia - Grade 3	29 Participants	2 Participants	1 Participants
Participants With Grade 3 or Grade 4 Hematology Parameters Neutropenia - Grade 3	103 Participants	24 Participants	10 Participants
Participants With Grade 3 or Grade 4 Hematology Parameters Lymphopenia - Grade 3	126 Participants	31 Participants	21 Participants
Participants With Grade 3 or Grade 4 Hematology Parameters Anemia - Grade 4	0 Participants	0 Participants	0 Participants
Participants With Grade 3 or Grade 4 Hematology Parameters Leukopenia - Grade 4	17 Participants	5 Participants	0 Participants
Participants With Grade 3 or Grade 4 Hematology Parameters Thrombocytopenia - Grade 4	7 Participants	0 Participants	0 Participants
Participants With Grade 3 or Grade 4 Hematology Parameters Neutropenia - Grade 4	94 Participants	25 Participants	6 Participants
Participants With Grade 3 or Grade 4 Hematology Parameters Lymphopenia - Grade 4	20 Participants	10 Participants	2 Participants

SECONDARY outcome

Timeframe: From first dose up to 30 days after last dose (up to approximately 64 weeks for induction period and 427 weeks for maintenance period)

Population: All treated participants

Clinical laboratory values in induction period include any laboratory values that are taken after the first dose date of induction therapy through 28 days after the last dose date of therapy. Graded according to the NCI CTCAE version 4.03, except for tumor flare reaction, which is accessed using NCI CTCAE version 3.0. Participants with zero maximum grade are excluded.

Outcome measures

Outcome measures
Measure	Arm A: Lenalidomide + Rituximab n=500 Participants Maintenance Period (18 Cycles): lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle for Cycles 13 to 30 AND rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29. Followed by Optional Maintenance Period (up to PD): Lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle up to PD. This treatment will be at the discretion of the participant and the investigator.	Arm B: Rituximab n=134 Participants Maintenance Period (18 Cycles): participants received rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29	Arm B: Rituximab n=132 Participants Maintenance Period (18 Cycles): participants received rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29
Participants With Grade 3 or Grade 4 Serum Chemistry Parameters Hyperuricemia - Grade 4	9 Participants	4 Participants	0 Participants
Participants With Grade 3 or Grade 4 Serum Chemistry Parameters Hypokalemia - Grade 3	30 Participants	8 Participants	4 Participants
Participants With Grade 3 or Grade 4 Serum Chemistry Parameters Hyperkalemia- Grade 3	4 Participants	0 Participants	1 Participants
Participants With Grade 3 or Grade 4 Serum Chemistry Parameters Hypocalcemia - Grade 3	7 Participants	1 Participants	0 Participants
Participants With Grade 3 or Grade 4 Serum Chemistry Parameters Hypercalcemia - Grade 3	7 Participants	0 Participants	0 Participants
Participants With Grade 3 or Grade 4 Serum Chemistry Parameters Hypophosphatemia - Grade 3	17 Participants	6 Participants	2 Participants
Participants With Grade 3 or Grade 4 Serum Chemistry Parameters Hypercreatininemia - Grade 3	3 Participants	1 Participants	0 Participants
Participants With Grade 3 or Grade 4 Serum Chemistry Parameters Hyperuricemia - Grade 3	40 Participants	13 Participants	20 Participants
Participants With Grade 3 or Grade 4 Serum Chemistry Parameters Alanine Aminotransferase Increased - Grade 3	14 Participants	3 Participants	0 Participants
Participants With Grade 3 or Grade 4 Serum Chemistry Parameters Aspartate Aminotransferase Increased - Grade 3	9 Participants	1 Participants	0 Participants
Participants With Grade 3 or Grade 4 Serum Chemistry Parameters Hyperbilirubinemia - Grade 3	5 Participants	3 Participants	1 Participants
Participants With Grade 3 or Grade 4 Serum Chemistry Parameters Hypokalemia - Grade 4	4 Participants	0 Participants	0 Participants
Participants With Grade 3 or Grade 4 Serum Chemistry Parameters Hyperkalemia- Grade 4	1 Participants	2 Participants	0 Participants
Participants With Grade 3 or Grade 4 Serum Chemistry Parameters Hypocalcemia - Grade 4	5 Participants	5 Participants	2 Participants
Participants With Grade 3 or Grade 4 Serum Chemistry Parameters Hypercalcemia - Grade 4	3 Participants	5 Participants	0 Participants
Participants With Grade 3 or Grade 4 Serum Chemistry Parameters Hypophosphatemia - Grade 4	1 Participants	1 Participants	1 Participants
Participants With Grade 3 or Grade 4 Serum Chemistry Parameters Hypercreatininemia - Grade 4	1 Participants	2 Participants	0 Participants
Participants With Grade 3 or Grade 4 Serum Chemistry Parameters Alanine Aminotransferase Increased - Grade 4	0 Participants	0 Participants	0 Participants
Participants With Grade 3 or Grade 4 Serum Chemistry Parameters Aspartate Aminotransferase Increased - Grade 4	0 Participants	0 Participants	0 Participants
Participants With Grade 3 or Grade 4 Serum Chemistry Parameters Hyperbilirubinemia - Grade 4	1 Participants	1 Participants	0 Participants

Adverse Events

Induction Period: Lenalidomide + Rituximab

Serious events: 172 serious events

Other events: 491 other events

Deaths: 112 deaths

Arm A: Lenalidomide + Rituximab

Serious events: 57 serious events

Other events: 129 other events

Deaths: 26 deaths

Arm B: Rituximab

Serious events: 22 serious events

Other events: 106 other events

Deaths: 32 deaths

Serious adverse events

Other adverse events

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: Please email

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER