Trial Outcomes & Findings for A Study to Determine the Efficacy of Lenalidomide Versus Investigator's Choice in Patients With Relapsed or Refractory Mantle Cell Lymphoma (MCL) (NCT NCT00875667)

Last Updated: 2019-09-16

Results Overview

PFS was defined as time of randomization to the first observation of disease progression or death due to any cause, whichever was first. If a participant had not progressed or died, PFS was censored at the time of last assessment when the participant was known not to have progressed. For participants who received other anti-lymphoma therapy with no evidence of progression, PFS was censored at time of last tumor assessment with no evidence of progression prior to the start of new anti-lymphoma treatment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

254 participants

Primary outcome timeframe

From randomization to progression of disease or death; up to data cut off date of 07 March 2014; overall median follow-up time was 93.9 weeks

Results posted on

2019-09-16

Participant Flow

The study was conducted at 67 sites including 3 sites in Belgium, 3 in Czech Republic, 14 in France, 7 in Germany, 2 in Israel, 10 in Italy, 1 in the Netherlands, 5 in Poland, 11 in Russia, 4 in Spain, 2 in Sweden, and 5 in the United Kingdom (UK).

Participants were randomized in a 2:1 ratio to receive lenalidomide monotherapy or investigator's choice. Participants were stratified according to the time since diagnosis (\< 3 years or ≥ 3 years), time since last treatment (\< 6 months \[refractory\] or ≥ 6 months) and if they had undergone a prior stem cell transplant or not.

Participant milestones

Participant milestones
Measure	Lenalidomide Participants received lenalidomide 25 mg capsules orally every day for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity. Participants with moderate renal insufficiency (creatinine clearance is ≥ 30 mL/min but \< 60mL/min received 10 mg lenalidomide for 21 days of each 28-day cycle (Cycles 1 and 2). After Cycle 2, if the participant remained free of Grade 3 or Grade 4 toxicity, the dose was increased to 15 mg lenalidomide for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Investigators Choice Participants received a single agent investigators choice (IC) of chlorambucil 40 mg/m\^2 PO every 28 days until progressive disease (PD) or toxicity, OR rituximab 375 mg/m\^2 by intravenous (IV) infusion on days 1, 8, 15 and 22 of each 56-day treatment cycle until PD or toxicity, OR cytarabine 1-2 g/m\^2 by IV infusion on days 1 and 2 of each 28 day treatment cycle; up to 6 cycles, OR gemcitabine 1000 mg/m\^2 by IV infusion on days 1, 8 and 15 of each 28 day treatment cycle; up to 6 cycles OR oral fludarabine 40 mg/m\^2 or IV fludarabine 25 mg/m\^2 on days 1 through 5 of each 28-day cycle; up to 6 cycles. Participants were given the option to enter into the lenalidomide crossover phase if PD occurred and received lenalidomide 25 mg capsules daily on days 1 to 21 of each 28 day treatment cycle until PD or toxicity.
Overall Study STARTED	170	84
Overall Study Crossover From IC to Lenalidomide	0	40
Overall Study Participants Treated	167	83
Overall Study COMPLETED	0	11
Overall Study NOT COMPLETED	170	73

Reasons for withdrawal

Reasons for withdrawal
Measure	Lenalidomide Participants received lenalidomide 25 mg capsules orally every day for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity. Participants with moderate renal insufficiency (creatinine clearance is ≥ 30 mL/min but \< 60mL/min received 10 mg lenalidomide for 21 days of each 28-day cycle (Cycles 1 and 2). After Cycle 2, if the participant remained free of Grade 3 or Grade 4 toxicity, the dose was increased to 15 mg lenalidomide for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Investigators Choice Participants received a single agent investigators choice (IC) of chlorambucil 40 mg/m\^2 PO every 28 days until progressive disease (PD) or toxicity, OR rituximab 375 mg/m\^2 by intravenous (IV) infusion on days 1, 8, 15 and 22 of each 56-day treatment cycle until PD or toxicity, OR cytarabine 1-2 g/m\^2 by IV infusion on days 1 and 2 of each 28 day treatment cycle; up to 6 cycles, OR gemcitabine 1000 mg/m\^2 by IV infusion on days 1, 8 and 15 of each 28 day treatment cycle; up to 6 cycles OR oral fludarabine 40 mg/m\^2 or IV fludarabine 25 mg/m\^2 on days 1 through 5 of each 28-day cycle; up to 6 cycles. Participants were given the option to enter into the lenalidomide crossover phase if PD occurred and received lenalidomide 25 mg capsules daily on days 1 to 21 of each 28 day treatment cycle until PD or toxicity.
Overall Study Adverse Event	29	10
Overall Study Withdrawal by Subject	17	5
Overall Study Death	7	2
Overall Study Protocol Violation	2	0
Overall Study Disease Progression	100	49
Overall Study Miscellaneous	12	6
Overall Study Randomized but no Study Drug Given	3	1

Baseline Characteristics

A Study to Determine the Efficacy of Lenalidomide Versus Investigator's Choice in Patients With Relapsed or Refractory Mantle Cell Lymphoma (MCL)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lenalidomide n=170 Participants Participants received lenalidomide 25 mg capsules orally every day for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity. Participants with moderate renal insufficiency (creatinine clearance is ≥ 30 mL/min but \< 60mL/min received 10 mg lenalidomide for 21 days of each 28-day cycle (Cycles 1 and 2). After Cycle 2, if the participant remained free of Grade 3 or Grade 4 toxicity, the dose was increased to 15 mg lenalidomide for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Investigators Choice n=84 Participants Participants received a single agent investigators choice (IC) of chlorambucil 40 mg/m\^2 PO every 28 days until progressive disease (PD) or toxicity, OR rituximab 375 mg/m\^2 by intravenous (IV) infusion on days 1, 8, 15 and 22 of each 56-day treatment cycle until PD or toxicity, OR cytarabine 1-2 g/m\^2 by IV infusion on days 1 and 2 of each 28 day treatment cycle; up to 6 cycles, OR gemcitabine 1000 mg/m\^2 by IV infusion on days 1, 8 and 15 of each 28 day treatment cycle; up to 6 cycles OR oral fludarabine 40 mg/m\^2 or IV fludarabine 25 mg/m\^2 on days 1 through 5 of each 28-day cycle; up to 6 cycles. Participants were given the option to enter into the lenalidomide crossover phase if PD occurred and received lenalidomide 25 mg capsules daily on days 1 to 21 of each 28 day treatment cycle until PD or toxicity.	Total n=254 Participants Total of all reporting groups
Stage of Mantle Cell Lymphoma (MCL) at Diagnosis Stage I	3 Participants n=99 Participants	2 Participants n=107 Participants	5 Participants n=206 Participants
Age, Continuous	68.0 Years STANDARD_DEVIATION 9.38 • n=99 Participants	67.5 Years STANDARD_DEVIATION 8.20 • n=107 Participants	67.8 Years STANDARD_DEVIATION 9.00 • n=206 Participants
Sex: Female, Male Female	47 Participants n=99 Participants	21 Participants n=107 Participants	68 Participants n=206 Participants
Sex: Female, Male Male	123 Participants n=99 Participants	63 Participants n=107 Participants	186 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) White	161 Participants n=99 Participants	80 Participants n=107 Participants	241 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	9 Participants n=99 Participants	4 Participants n=107 Participants	13 Participants n=206 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 = Fully Active	65 Participants n=99 Participants	36 Participants n=107 Participants	101 Participants n=206 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1 = Restrictive but Ambulatory	77 Participants n=99 Participants	37 Participants n=107 Participants	114 Participants n=206 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2 = Ambulatory but Unable to Work	27 Participants n=99 Participants	11 Participants n=107 Participants	38 Participants n=206 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 3 = Limited Self-Care	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Missing	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Stage of Mantle Cell Lymphoma (MCL) at Diagnosis Stage II	10 Participants n=99 Participants	1 Participants n=107 Participants	11 Participants n=206 Participants
Stage of Mantle Cell Lymphoma (MCL) at Diagnosis Stage III	30 Participants n=99 Participants	20 Participants n=107 Participants	50 Participants n=206 Participants
Stage of Mantle Cell Lymphoma (MCL) at Diagnosis Stage IV	123 Participants n=99 Participants	59 Participants n=107 Participants	182 Participants n=206 Participants
Stage of Mantle Cell Lymphoma (MCL) at Diagnosis Missing	4 Participants n=99 Participants	2 Participants n=107 Participants	6 Participants n=206 Participants
MCL International Prognostic Index (MIPI) Score at Baseline Low Risk	42 Participants n=99 Participants	21 Participants n=107 Participants	63 Participants n=206 Participants
MCL International Prognostic Index (MIPI) Score at Baseline Intermediate Risk	66 Participants n=99 Participants	37 Participants n=107 Participants	103 Participants n=206 Participants
MCL International Prognostic Index (MIPI) Score at Baseline High Risk	60 Participants n=99 Participants	25 Participants n=107 Participants	85 Participants n=206 Participants
MCL International Prognostic Index (MIPI) Score at Baseline Missing	2 Participants n=99 Participants	1 Participants n=107 Participants	3 Participants n=206 Participants
Bone Marrow Involvment as Baseline Negative	27 Participants n=99 Participants	11 Participants n=107 Participants	38 Participants n=206 Participants
Bone Marrow Involvment as Baseline Intermediate	4 Participants n=99 Participants	3 Participants n=107 Participants	7 Participants n=206 Participants
Bone Marrow Involvment as Baseline Positive	21 Participants n=99 Participants	13 Participants n=107 Participants	34 Participants n=206 Participants
Bone Marrow Involvment as Baseline Missing	118 Participants n=99 Participants	57 Participants n=107 Participants	175 Participants n=206 Participants

PRIMARY outcome

Timeframe: From randomization to progression of disease or death; up to data cut off date of 07 March 2014; overall median follow-up time was 93.9 weeks

Population: ITT population included all randomized participants.

Outcome measures

Outcome measures
Measure	Investigators Choice n=84 Participants Participants received a single agent investigators choice (IC) of chlorambucil 40 mg/m\^2 PO every 28 days until progressive disease (PD) or toxicity, OR rituximab 375 mg/m\^2 by intravenous (IV) infusion on days 1, 8, 15 and 22 of each 56-day treatment cycle until PD or toxicity, OR cytarabine 1-2 g/m\^2 by IV infusion on days 1 and 2 of each 28 day treatment cycle; up to 6 cycles, OR gemcitabine 1000 mg/m\^2 by IV infusion on days 1, 8 and 15 of each 28 day treatment cycle; up to 6 cycles OR oral fludarabine 40 mg/m\^2 or IV fludarabine 25 mg/m\^2 on days 1 through 5 of each 28-day cycle; up to 6 cycles. Participants were given the option to enter into the lenalidomide crossover phase if PD occurred and received lenalidomide 25 mg capsules daily on days 1 to 21 of each 28 day treatment cycle until PD or toxicity.	Lenalidomide n=170 Participants Participants received lenalidomide 25 mg capsules orally every day for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity. Participants with moderate renal insufficiency (creatinine clearance is ≥ 30 mL/min but \< 60mL/min received 10 mg lenalidomide for 21 days of each 28-day cycle (Cycles 1 and 2). After Cycle 2, if the participant remained free of Grade 3 or Grade 4 toxicity, the dose was increased to 15 mg lenalidomide for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Kaplan Meier Estimate for Progression Free Survival (PFS) by Independent Review Committee (IRC) Central Review	22.7 weeks Interval 15.9 to 30.1	37.6 weeks Interval 24.0 to 52.6

PRIMARY outcome

Timeframe: From randomization to progression of disease or death; up to study discontinuation of 09 October 2018; overall median follow-up time was 285 weeks

Population: ITT population included all randomized participants.

Kaplan Meier estimates of PFS were defined as the time from randomization to the first observation of disease progression or death due to any cause, whichever was first. If a participant had not progressed or died, PFS was censored at the time of last completed assessment when the participant was known not to have progressed. For participants who received other anti-lymphoma therapy with no evidence of progression, PFS was censored at time of last tumor assessment with no evidence of progression prior to the start of new anti-lymphoma treatment.

Outcome measures

Outcome measures
Measure	Investigators Choice n=84 Participants Participants received a single agent investigators choice (IC) of chlorambucil 40 mg/m\^2 PO every 28 days until progressive disease (PD) or toxicity, OR rituximab 375 mg/m\^2 by intravenous (IV) infusion on days 1, 8, 15 and 22 of each 56-day treatment cycle until PD or toxicity, OR cytarabine 1-2 g/m\^2 by IV infusion on days 1 and 2 of each 28 day treatment cycle; up to 6 cycles, OR gemcitabine 1000 mg/m\^2 by IV infusion on days 1, 8 and 15 of each 28 day treatment cycle; up to 6 cycles OR oral fludarabine 40 mg/m\^2 or IV fludarabine 25 mg/m\^2 on days 1 through 5 of each 28-day cycle; up to 6 cycles. Participants were given the option to enter into the lenalidomide crossover phase if PD occurred and received lenalidomide 25 mg capsules daily on days 1 to 21 of each 28 day treatment cycle until PD or toxicity.	Lenalidomide n=170 Participants Participants received lenalidomide 25 mg capsules orally every day for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity. Participants with moderate renal insufficiency (creatinine clearance is ≥ 30 mL/min but \< 60mL/min received 10 mg lenalidomide for 21 days of each 28-day cycle (Cycles 1 and 2). After Cycle 2, if the participant remained free of Grade 3 or Grade 4 toxicity, the dose was increased to 15 mg lenalidomide for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Kaplan Meier Estimate for Progression Free Survival by Investigator's Assessment at the Final Analysis	23.6 weeks Interval 15.9 to 33.3	37.3 weeks Interval 24.1 to 52.6

SECONDARY outcome

Timeframe: From date of randomization to the data cut-off date of 07 March 2014; median treatment duration was 24.3 weeks for the lenalidomide arm and 13.1 weeks for the investigators choice arm

Population: ITT population included all randomized participants.

Overall Response Rate (ORR) was defined as the percentage of participants whose best response was Complete Response (CR), Complete Response unconfirmed (CRu) or Partial Response (PR). Participants who discontinued before any response had been observed or changed to other anti-lymphoma treatments before response had been observed, were considered as non-responders. Tumor Response was assessed by a modification of the International Lymphoma Workshop Response Criteria, IWRC, Cheson, 1999; CR is defined as the disappearance of all clinical and radiographic evidence of disease; CRu is defined as a CR, with a 1) residual lymph node mass \>1.5 cm that has decreased by 75% in the sum of the product of the diameters (SPD). Individual nodes previously confluent decreased by more than 75% in the SPD compared with original mass; 2) indeterminate bone marrow; PR = is defined ≥50% decrease in 6 largest nodes or nodal masses.

Outcome measures

Outcome measures
Measure	Investigators Choice n=84 Participants Participants received a single agent investigators choice (IC) of chlorambucil 40 mg/m\^2 PO every 28 days until progressive disease (PD) or toxicity, OR rituximab 375 mg/m\^2 by intravenous (IV) infusion on days 1, 8, 15 and 22 of each 56-day treatment cycle until PD or toxicity, OR cytarabine 1-2 g/m\^2 by IV infusion on days 1 and 2 of each 28 day treatment cycle; up to 6 cycles, OR gemcitabine 1000 mg/m\^2 by IV infusion on days 1, 8 and 15 of each 28 day treatment cycle; up to 6 cycles OR oral fludarabine 40 mg/m\^2 or IV fludarabine 25 mg/m\^2 on days 1 through 5 of each 28-day cycle; up to 6 cycles. Participants were given the option to enter into the lenalidomide crossover phase if PD occurred and received lenalidomide 25 mg capsules daily on days 1 to 21 of each 28 day treatment cycle until PD or toxicity.	Lenalidomide n=170 Participants Participants received lenalidomide 25 mg capsules orally every day for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity. Participants with moderate renal insufficiency (creatinine clearance is ≥ 30 mL/min but \< 60mL/min received 10 mg lenalidomide for 21 days of each 28-day cycle (Cycles 1 and 2). After Cycle 2, if the participant remained free of Grade 3 or Grade 4 toxicity, the dose was increased to 15 mg lenalidomide for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Percentage of Participants Who Achieved an Overall Response According to the IRC Central Review	10.7 Percentage of Participants Interval 5.02 to 19.37	40.0 Percentage of Participants Interval 32.58 to 47.78

SECONDARY outcome

Timeframe: From date of randomization to the study discontinuation date of 09 October 2018; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm

Population: ITT population included all randomized participants.

Overall Response Rate (ORR) was defined as the percentage of participants whose best response was Complete Response, Complete Response unconfirmed or Partial Response. Participants who had discontinued before any response has been observed or changed to other anti-lymphoma treatments before response had been observed, were considered as non-responders. Tumor Response was assessed by a modification of the International Lymphoma Workshop Response Criteria, IWRC, Cheson, 1999; CR is defined as the disappearance of all clinical and radiographic evidence of disease; CRu is defined as a CR, with a 1) residual lymph node mass \>1.5 cm that has decreased by 75% in the sum of the product of the diameters (SPD). Individual nodes previously confluent decreased by more than 75% in the SPD compared with original mass; 2) indeterminate bone marrow; PR = is defined ≥50% decrease in 6 largest nodes or nodal masses.

Outcome measures

Outcome measures
Measure	Investigators Choice n=84 Participants Participants received a single agent investigators choice (IC) of chlorambucil 40 mg/m\^2 PO every 28 days until progressive disease (PD) or toxicity, OR rituximab 375 mg/m\^2 by intravenous (IV) infusion on days 1, 8, 15 and 22 of each 56-day treatment cycle until PD or toxicity, OR cytarabine 1-2 g/m\^2 by IV infusion on days 1 and 2 of each 28 day treatment cycle; up to 6 cycles, OR gemcitabine 1000 mg/m\^2 by IV infusion on days 1, 8 and 15 of each 28 day treatment cycle; up to 6 cycles OR oral fludarabine 40 mg/m\^2 or IV fludarabine 25 mg/m\^2 on days 1 through 5 of each 28-day cycle; up to 6 cycles. Participants were given the option to enter into the lenalidomide crossover phase if PD occurred and received lenalidomide 25 mg capsules daily on days 1 to 21 of each 28 day treatment cycle until PD or toxicity.	Lenalidomide n=170 Participants Participants received lenalidomide 25 mg capsules orally every day for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity. Participants with moderate renal insufficiency (creatinine clearance is ≥ 30 mL/min but \< 60mL/min received 10 mg lenalidomide for 21 days of each 28-day cycle (Cycles 1 and 2). After Cycle 2, if the participant remained free of Grade 3 or Grade 4 toxicity, the dose was increased to 15 mg lenalidomide for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Percentage of Participants Who Achieved an Overall Response as Assessed by the Investigator at the Final Analysis	22.6 Percentage of Participants Interval 14.2 to 33.05	45.9 Percentage of Participants Interval 38.23 to 53.68

SECONDARY outcome

Timeframe: From date of randomization to the data cut-off date of 07 March 2014; median study duration was 70.7 weeks for the lenalidomide arm and 69.3 weeks for the investigators choice arm

Population: The analysis population included participants with an overall response.

Duration of response was defined as the time from when the first response of CR, CRu, or PR was first achieved until documented tumor progression, or until the participant died from any cause, whichever occurred first. Participants who did not progress or die at the time of analysis were censored at the last assessment date that the participant was known to be progression-free. Participants who received a new treatment without documented progression were censored at the last assessment date that the participant was known to be progression-free.

Outcome measures

Outcome measures
Measure	Investigators Choice n=9 Participants Participants received a single agent investigators choice (IC) of chlorambucil 40 mg/m\^2 PO every 28 days until progressive disease (PD) or toxicity, OR rituximab 375 mg/m\^2 by intravenous (IV) infusion on days 1, 8, 15 and 22 of each 56-day treatment cycle until PD or toxicity, OR cytarabine 1-2 g/m\^2 by IV infusion on days 1 and 2 of each 28 day treatment cycle; up to 6 cycles, OR gemcitabine 1000 mg/m\^2 by IV infusion on days 1, 8 and 15 of each 28 day treatment cycle; up to 6 cycles OR oral fludarabine 40 mg/m\^2 or IV fludarabine 25 mg/m\^2 on days 1 through 5 of each 28-day cycle; up to 6 cycles. Participants were given the option to enter into the lenalidomide crossover phase if PD occurred and received lenalidomide 25 mg capsules daily on days 1 to 21 of each 28 day treatment cycle until PD or toxicity.	Lenalidomide n=68 Participants Participants received lenalidomide 25 mg capsules orally every day for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity. Participants with moderate renal insufficiency (creatinine clearance is ≥ 30 mL/min but \< 60mL/min received 10 mg lenalidomide for 21 days of each 28-day cycle (Cycles 1 and 2). After Cycle 2, if the participant remained free of Grade 3 or Grade 4 toxicity, the dose was increased to 15 mg lenalidomide for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Kaplan Meier Estimate for Duration of Response (DOR) According to the IRC Central Review	45.1 Weeks Interval 36.3 to 80.9	69.6 Weeks Interval 41.1 to 86.7

SECONDARY outcome

Timeframe: From date of randomization to the study discontinuation date of 09 October 2018; median study duration was 103.9 weeks for lenalidomide and 87.0 weeks for the investigator choice arm

Population: The analysis population included participants with an overall response.

Outcome measures

Outcome measures
Measure	Investigators Choice n=19 Participants Participants received a single agent investigators choice (IC) of chlorambucil 40 mg/m\^2 PO every 28 days until progressive disease (PD) or toxicity, OR rituximab 375 mg/m\^2 by intravenous (IV) infusion on days 1, 8, 15 and 22 of each 56-day treatment cycle until PD or toxicity, OR cytarabine 1-2 g/m\^2 by IV infusion on days 1 and 2 of each 28 day treatment cycle; up to 6 cycles, OR gemcitabine 1000 mg/m\^2 by IV infusion on days 1, 8 and 15 of each 28 day treatment cycle; up to 6 cycles OR oral fludarabine 40 mg/m\^2 or IV fludarabine 25 mg/m\^2 on days 1 through 5 of each 28-day cycle; up to 6 cycles. Participants were given the option to enter into the lenalidomide crossover phase if PD occurred and received lenalidomide 25 mg capsules daily on days 1 to 21 of each 28 day treatment cycle until PD or toxicity.	Lenalidomide n=78 Participants Participants received lenalidomide 25 mg capsules orally every day for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity. Participants with moderate renal insufficiency (creatinine clearance is ≥ 30 mL/min but \< 60mL/min received 10 mg lenalidomide for 21 days of each 28-day cycle (Cycles 1 and 2). After Cycle 2, if the participant remained free of Grade 3 or Grade 4 toxicity, the dose was increased to 15 mg lenalidomide for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Kaplan Meier Estimate for Duration of Response as Assessed by the Investigator at the Final Analysis	91.7 Weeks Interval 28.3 to 130.1	70.1 Weeks Interval 47.0 to 98.0

SECONDARY outcome

Timeframe: From date of randomization to the data cut-off date of 07 March 2014; median treatment duration was 24.3 weeks for the lenalidomide arm and 13.1 weeks for the investigators choice arm

Population: ITT population includes all randomized participants.

Tumor control rate was defined as the percentage of participants with a complete response (CR), unconfirmed complete response (CRu), partial response (PR) and stable disease (SD). Tumor Response was assessed by a modification of the International Lymphoma Workshop Response Criteria, IWRC, Cheson, 1999); CR is defined as the disappearance of all clinical and radiographic evidence of disease; CRu is defined as a CR, with a 1) residual lymph node mass \>1.5 cm that has decreased by 75% in the sum of the product of the diameters (SPD). Individual nodes previously confluent decreased by more than 75% in the SPD compared with original mass; 2) indeterminate bone marrow; PR = is defined ≥50% decrease in 6 largest nodes or nodal masses. Stable disease (SD) is defined as less than a PR (see above) but is not progressive disease or relapsed disease.

Outcome measures

Outcome measures
Measure	Investigators Choice n=84 Participants Participants received a single agent investigators choice (IC) of chlorambucil 40 mg/m\^2 PO every 28 days until progressive disease (PD) or toxicity, OR rituximab 375 mg/m\^2 by intravenous (IV) infusion on days 1, 8, 15 and 22 of each 56-day treatment cycle until PD or toxicity, OR cytarabine 1-2 g/m\^2 by IV infusion on days 1 and 2 of each 28 day treatment cycle; up to 6 cycles, OR gemcitabine 1000 mg/m\^2 by IV infusion on days 1, 8 and 15 of each 28 day treatment cycle; up to 6 cycles OR oral fludarabine 40 mg/m\^2 or IV fludarabine 25 mg/m\^2 on days 1 through 5 of each 28-day cycle; up to 6 cycles. Participants were given the option to enter into the lenalidomide crossover phase if PD occurred and received lenalidomide 25 mg capsules daily on days 1 to 21 of each 28 day treatment cycle until PD or toxicity.	Lenalidomide n=170 Participants Participants received lenalidomide 25 mg capsules orally every day for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity. Participants with moderate renal insufficiency (creatinine clearance is ≥ 30 mL/min but \< 60mL/min received 10 mg lenalidomide for 21 days of each 28-day cycle (Cycles 1 and 2). After Cycle 2, if the participant remained free of Grade 3 or Grade 4 toxicity, the dose was increased to 15 mg lenalidomide for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Percentage of Participants With a Complete Response, Unconfirmed Complete Response, Partial Response and Stable Disease According to the IRC Central Review	63.1 Percentage of Participants Interval 51.87 to 73.37	69.4 Percentage of Participants Interval 61.89 to 76.24

SECONDARY outcome

Timeframe: From date of randomization to the discontinuation date of 09 October 2018; median treatment duration was 24.3 weeks for the lenalidomide arm and 13.1 weeks for the investigators choice arm

Population: ITT population includes all randomized participants.

Outcome measures

Outcome measures
Measure	Investigators Choice n=84 Participants Participants received a single agent investigators choice (IC) of chlorambucil 40 mg/m\^2 PO every 28 days until progressive disease (PD) or toxicity, OR rituximab 375 mg/m\^2 by intravenous (IV) infusion on days 1, 8, 15 and 22 of each 56-day treatment cycle until PD or toxicity, OR cytarabine 1-2 g/m\^2 by IV infusion on days 1 and 2 of each 28 day treatment cycle; up to 6 cycles, OR gemcitabine 1000 mg/m\^2 by IV infusion on days 1, 8 and 15 of each 28 day treatment cycle; up to 6 cycles OR oral fludarabine 40 mg/m\^2 or IV fludarabine 25 mg/m\^2 on days 1 through 5 of each 28-day cycle; up to 6 cycles. Participants were given the option to enter into the lenalidomide crossover phase if PD occurred and received lenalidomide 25 mg capsules daily on days 1 to 21 of each 28 day treatment cycle until PD or toxicity.	Lenalidomide n=170 Participants Participants received lenalidomide 25 mg capsules orally every day for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity. Participants with moderate renal insufficiency (creatinine clearance is ≥ 30 mL/min but \< 60mL/min received 10 mg lenalidomide for 21 days of each 28-day cycle (Cycles 1 and 2). After Cycle 2, if the participant remained free of Grade 3 or Grade 4 toxicity, the dose was increased to 15 mg lenalidomide for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Percentage of Participants With a Complete Response, Unconfirmed Complete Response, Partial Response and Stable Disease at the Final Analysis	65.5 Percentage of participants Interval 54.31 to 75.52	70.0 Percentage of participants Interval 62.51 to 76.78

SECONDARY outcome

Timeframe: From date of randomization to the data cut-off date of 07 March 2014; median study duration was 70.7 weeks for the lenalidomide arm and 69.3 weeks for the investigators choice arm

Population: ITT population includes all randomized participants.

Time to progression (TTP) was defined as the time from randomization until objective tumor progression. Time to progression did not include deaths. Participants without progression at the time of analysis were censored at the last assessment date that the participant was known to be progression-free. Participants who received a new anti-lymphoma treatment without documented progression were censored at the last assessment date that the participant was known to be progression-free.

Outcome measures

Outcome measures
Measure	Investigators Choice n=84 Participants Participants received a single agent investigators choice (IC) of chlorambucil 40 mg/m\^2 PO every 28 days until progressive disease (PD) or toxicity, OR rituximab 375 mg/m\^2 by intravenous (IV) infusion on days 1, 8, 15 and 22 of each 56-day treatment cycle until PD or toxicity, OR cytarabine 1-2 g/m\^2 by IV infusion on days 1 and 2 of each 28 day treatment cycle; up to 6 cycles, OR gemcitabine 1000 mg/m\^2 by IV infusion on days 1, 8 and 15 of each 28 day treatment cycle; up to 6 cycles OR oral fludarabine 40 mg/m\^2 or IV fludarabine 25 mg/m\^2 on days 1 through 5 of each 28-day cycle; up to 6 cycles. Participants were given the option to enter into the lenalidomide crossover phase if PD occurred and received lenalidomide 25 mg capsules daily on days 1 to 21 of each 28 day treatment cycle until PD or toxicity.	Lenalidomide n=170 Participants Participants received lenalidomide 25 mg capsules orally every day for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity. Participants with moderate renal insufficiency (creatinine clearance is ≥ 30 mL/min but \< 60mL/min received 10 mg lenalidomide for 21 days of each 28-day cycle (Cycles 1 and 2). After Cycle 2, if the participant remained free of Grade 3 or Grade 4 toxicity, the dose was increased to 15 mg lenalidomide for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Kaplan Meier Estimate of Time to Progression According to the IRC Central Review	24.7 Weeks Interval 15.9 to 30.1	39.3 Weeks Interval 24.3 to 52.9

SECONDARY outcome

Timeframe: From date of randomization to the study discontinuation date of 09 October 2018; median study duration was 103.9 weeks for lenalidomide and 87.0 weeks for the investigator choice arm

Population: ITT population includes all randomized participants.

Outcome measures

Outcome measures
Measure	Investigators Choice n=84 Participants Participants received a single agent investigators choice (IC) of chlorambucil 40 mg/m\^2 PO every 28 days until progressive disease (PD) or toxicity, OR rituximab 375 mg/m\^2 by intravenous (IV) infusion on days 1, 8, 15 and 22 of each 56-day treatment cycle until PD or toxicity, OR cytarabine 1-2 g/m\^2 by IV infusion on days 1 and 2 of each 28 day treatment cycle; up to 6 cycles, OR gemcitabine 1000 mg/m\^2 by IV infusion on days 1, 8 and 15 of each 28 day treatment cycle; up to 6 cycles OR oral fludarabine 40 mg/m\^2 or IV fludarabine 25 mg/m\^2 on days 1 through 5 of each 28-day cycle; up to 6 cycles. Participants were given the option to enter into the lenalidomide crossover phase if PD occurred and received lenalidomide 25 mg capsules daily on days 1 to 21 of each 28 day treatment cycle until PD or toxicity.	Lenalidomide n=170 Participants Participants received lenalidomide 25 mg capsules orally every day for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity. Participants with moderate renal insufficiency (creatinine clearance is ≥ 30 mL/min but \< 60mL/min received 10 mg lenalidomide for 21 days of each 28-day cycle (Cycles 1 and 2). After Cycle 2, if the participant remained free of Grade 3 or Grade 4 toxicity, the dose was increased to 15 mg lenalidomide for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Kaplan Meier Estimate of Time to Progression as Assessed by the Investigator at the Final Analysis	24.7 Weeks Interval 15.9 to 36.7	39.3 Weeks Interval 25.1 to 61.0

SECONDARY outcome

Timeframe: From the date of the first treatment to the data cut-off date of 07 March 2014; median treatment duration was 24.3 weeks for the lenalidomide arm and 13.1 weeks for the investigators choice arm

Population: Includes all treated participants.

Time to treatment failure was defined as the time from the first dose of study drug to discontinuation of treatment for any reason, including disease progression assessed by the investigator, treatment toxicity, or death. Participants who were on-treatment or completed the treatment according to the protocol were censored at the last date of drug intake.

Outcome measures

Outcome measures
Measure	Investigators Choice n=83 Participants Participants received a single agent investigators choice (IC) of chlorambucil 40 mg/m\^2 PO every 28 days until progressive disease (PD) or toxicity, OR rituximab 375 mg/m\^2 by intravenous (IV) infusion on days 1, 8, 15 and 22 of each 56-day treatment cycle until PD or toxicity, OR cytarabine 1-2 g/m\^2 by IV infusion on days 1 and 2 of each 28 day treatment cycle; up to 6 cycles, OR gemcitabine 1000 mg/m\^2 by IV infusion on days 1, 8 and 15 of each 28 day treatment cycle; up to 6 cycles OR oral fludarabine 40 mg/m\^2 or IV fludarabine 25 mg/m\^2 on days 1 through 5 of each 28-day cycle; up to 6 cycles. Participants were given the option to enter into the lenalidomide crossover phase if PD occurred and received lenalidomide 25 mg capsules daily on days 1 to 21 of each 28 day treatment cycle until PD or toxicity.	Lenalidomide n=167 Participants Participants received lenalidomide 25 mg capsules orally every day for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity. Participants with moderate renal insufficiency (creatinine clearance is ≥ 30 mL/min but \< 60mL/min received 10 mg lenalidomide for 21 days of each 28-day cycle (Cycles 1 and 2). After Cycle 2, if the participant remained free of Grade 3 or Grade 4 toxicity, the dose was increased to 15 mg lenalidomide for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Kaplan Meier Estimate of Time to Treatment Failure (TTF) as Assessed by the Investigator	17.9 weeks Interval 14.1 to 24.9	24.4 weeks Interval 17.1 to 37.6

SECONDARY outcome

Timeframe: From date of first dose of treatment to the study discontinuation date of 09 October 2018; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm

Population: Includes all treated participants.

Outcome measures

Outcome measures
Measure	Investigators Choice n=83 Participants Participants received a single agent investigators choice (IC) of chlorambucil 40 mg/m\^2 PO every 28 days until progressive disease (PD) or toxicity, OR rituximab 375 mg/m\^2 by intravenous (IV) infusion on days 1, 8, 15 and 22 of each 56-day treatment cycle until PD or toxicity, OR cytarabine 1-2 g/m\^2 by IV infusion on days 1 and 2 of each 28 day treatment cycle; up to 6 cycles, OR gemcitabine 1000 mg/m\^2 by IV infusion on days 1, 8 and 15 of each 28 day treatment cycle; up to 6 cycles OR oral fludarabine 40 mg/m\^2 or IV fludarabine 25 mg/m\^2 on days 1 through 5 of each 28-day cycle; up to 6 cycles. Participants were given the option to enter into the lenalidomide crossover phase if PD occurred and received lenalidomide 25 mg capsules daily on days 1 to 21 of each 28 day treatment cycle until PD or toxicity.	Lenalidomide n=167 Participants Participants received lenalidomide 25 mg capsules orally every day for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity. Participants with moderate renal insufficiency (creatinine clearance is ≥ 30 mL/min but \< 60mL/min received 10 mg lenalidomide for 21 days of each 28-day cycle (Cycles 1 and 2). After Cycle 2, if the participant remained free of Grade 3 or Grade 4 toxicity, the dose was increased to 15 mg lenalidomide for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Kaplan Meier Estimate of Time to Treatment Failure as Assessed by the Investigator at the Final Analysis	17.9 weeks Interval 14.1 to 24.9	24.4 weeks Interval 17.1 to 37.6

SECONDARY outcome

Timeframe: From randomization of study drug to time of first documented PR or better response; up to data cut-off date of 07 March 2014; median treatment duration was 24.3 weeks for the lenalidomide arm and 13.1 weeks for the investigators choice arm

Population: ITT population includes all randomized participants.

Time to Response was defined as the time from first dose of study drug to the date of the first response (having at least a PR) and was calculated only for responding participants. ). Participants with progression at the time of analysis were censored at the first assessment date that the participant was known to have progressed. Participants with SD at the time of analysis were censored at the last assessment date that the participant was known to be progression-free.

Outcome measures

Outcome measures
Measure	Investigators Choice n=84 Participants Participants received a single agent investigators choice (IC) of chlorambucil 40 mg/m\^2 PO every 28 days until progressive disease (PD) or toxicity, OR rituximab 375 mg/m\^2 by intravenous (IV) infusion on days 1, 8, 15 and 22 of each 56-day treatment cycle until PD or toxicity, OR cytarabine 1-2 g/m\^2 by IV infusion on days 1 and 2 of each 28 day treatment cycle; up to 6 cycles, OR gemcitabine 1000 mg/m\^2 by IV infusion on days 1, 8 and 15 of each 28 day treatment cycle; up to 6 cycles OR oral fludarabine 40 mg/m\^2 or IV fludarabine 25 mg/m\^2 on days 1 through 5 of each 28-day cycle; up to 6 cycles. Participants were given the option to enter into the lenalidomide crossover phase if PD occurred and received lenalidomide 25 mg capsules daily on days 1 to 21 of each 28 day treatment cycle until PD or toxicity.	Lenalidomide n=170 Participants Participants received lenalidomide 25 mg capsules orally every day for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity. Participants with moderate renal insufficiency (creatinine clearance is ≥ 30 mL/min but \< 60mL/min received 10 mg lenalidomide for 21 days of each 28-day cycle (Cycles 1 and 2). After Cycle 2, if the participant remained free of Grade 3 or Grade 4 toxicity, the dose was increased to 15 mg lenalidomide for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Kaplan Meier Estimate of Time to First Response (TTFR) According to the IRC Central Review	NA Weeks Interval 63.9 to Not estimable due to the low number of participants with a response.	18.7 Weeks Interval 16.7 to 49.7

SECONDARY outcome

Timeframe: From date of randomization to the study discontinuation date of 09 October 2018; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm

Population: ITT population includes all randomized participants.

Time to first response was defined as the time from first dose of study drug to the date of the first response (having at least a PR). Participants with progression at the time of analysis were censored at the first assessment date that the participant was known to have progressed. Participants with SD at the time of analysis were censored at the last assessment date that the subject was known to be progression-free.

Outcome measures

Outcome measures
Measure	Investigators Choice n=84 Participants Participants received a single agent investigators choice (IC) of chlorambucil 40 mg/m\^2 PO every 28 days until progressive disease (PD) or toxicity, OR rituximab 375 mg/m\^2 by intravenous (IV) infusion on days 1, 8, 15 and 22 of each 56-day treatment cycle until PD or toxicity, OR cytarabine 1-2 g/m\^2 by IV infusion on days 1 and 2 of each 28 day treatment cycle; up to 6 cycles, OR gemcitabine 1000 mg/m\^2 by IV infusion on days 1, 8 and 15 of each 28 day treatment cycle; up to 6 cycles OR oral fludarabine 40 mg/m\^2 or IV fludarabine 25 mg/m\^2 on days 1 through 5 of each 28-day cycle; up to 6 cycles. Participants were given the option to enter into the lenalidomide crossover phase if PD occurred and received lenalidomide 25 mg capsules daily on days 1 to 21 of each 28 day treatment cycle until PD or toxicity.	Lenalidomide n=170 Participants Participants received lenalidomide 25 mg capsules orally every day for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity. Participants with moderate renal insufficiency (creatinine clearance is ≥ 30 mL/min but \< 60mL/min received 10 mg lenalidomide for 21 days of each 28-day cycle (Cycles 1 and 2). After Cycle 2, if the participant remained free of Grade 3 or Grade 4 toxicity, the dose was increased to 15 mg lenalidomide for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Kaplan Meier Estimate of Time to First Response as Assessed by the Investigator at the Final Analysis	40.0 Weeks Interval 25.6 to Upper Limit not estimable due to the low number of participants with a response.	23.9 Weeks Interval 16.7 to 25.6

SECONDARY outcome

Timeframe: From date of randomization to the data cut-off date of 07 March 2014; overall median follow-up was 93.9 weeks

Population: ITT population included all randomized participants.

Overall survival was defined as the time from randomization until death from any cause. Participants alive or lost to follow-up at the time of analysis were censored at the last date they were known to be alive.

Outcome measures

Outcome measures
Measure	Investigators Choice n=84 Participants Participants received a single agent investigators choice (IC) of chlorambucil 40 mg/m\^2 PO every 28 days until progressive disease (PD) or toxicity, OR rituximab 375 mg/m\^2 by intravenous (IV) infusion on days 1, 8, 15 and 22 of each 56-day treatment cycle until PD or toxicity, OR cytarabine 1-2 g/m\^2 by IV infusion on days 1 and 2 of each 28 day treatment cycle; up to 6 cycles, OR gemcitabine 1000 mg/m\^2 by IV infusion on days 1, 8 and 15 of each 28 day treatment cycle; up to 6 cycles OR oral fludarabine 40 mg/m\^2 or IV fludarabine 25 mg/m\^2 on days 1 through 5 of each 28-day cycle; up to 6 cycles. Participants were given the option to enter into the lenalidomide crossover phase if PD occurred and received lenalidomide 25 mg capsules daily on days 1 to 21 of each 28 day treatment cycle until PD or toxicity.	Lenalidomide n=170 Participants Participants received lenalidomide 25 mg capsules orally every day for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity. Participants with moderate renal insufficiency (creatinine clearance is ≥ 30 mL/min but \< 60mL/min received 10 mg lenalidomide for 21 days of each 28-day cycle (Cycles 1 and 2). After Cycle 2, if the participant remained free of Grade 3 or Grade 4 toxicity, the dose was increased to 15 mg lenalidomide for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Kaplan Meier Estimate for Overall Survival (OS) According to the IRC Central Review	91.7 weeks Interval 69.4 to 125.6	121.0 weeks Interval 86.7 to 160.4

SECONDARY outcome

Timeframe: From randomization to progression of disease or death; up to the study discontinuation date of 09 October 2018; overall median follow-up time was 285 weeks

Population: ITT population included all randomized participants.

Outcome measures

Outcome measures
Measure	Investigators Choice n=84 Participants Participants received a single agent investigators choice (IC) of chlorambucil 40 mg/m\^2 PO every 28 days until progressive disease (PD) or toxicity, OR rituximab 375 mg/m\^2 by intravenous (IV) infusion on days 1, 8, 15 and 22 of each 56-day treatment cycle until PD or toxicity, OR cytarabine 1-2 g/m\^2 by IV infusion on days 1 and 2 of each 28 day treatment cycle; up to 6 cycles, OR gemcitabine 1000 mg/m\^2 by IV infusion on days 1, 8 and 15 of each 28 day treatment cycle; up to 6 cycles OR oral fludarabine 40 mg/m\^2 or IV fludarabine 25 mg/m\^2 on days 1 through 5 of each 28-day cycle; up to 6 cycles. Participants were given the option to enter into the lenalidomide crossover phase if PD occurred and received lenalidomide 25 mg capsules daily on days 1 to 21 of each 28 day treatment cycle until PD or toxicity.	Lenalidomide n=170 Participants Participants received lenalidomide 25 mg capsules orally every day for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity. Participants with moderate renal insufficiency (creatinine clearance is ≥ 30 mL/min but \< 60mL/min received 10 mg lenalidomide for 21 days of each 28-day cycle (Cycles 1 and 2). After Cycle 2, if the participant remained free of Grade 3 or Grade 4 toxicity, the dose was increased to 15 mg lenalidomide for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Kaplan Meier Estimate for Overall Survival as Assessed by the Investigator at the Final Analysis	91.7 weeks Interval 69.4 to 137.3	120.6 weeks Interval 98.1 to 153.0

SECONDARY outcome

Timeframe: From the date of the first dose of study drug to 28 days after the last dose, up to the study discontinuation date of 09 October 2018; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigators choice arm

Population: The safety population included participants who received at least one dose of study drug (either lenalidomide or investigator's choice).

Adverse events were assessed using National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 3: according to the following scale: Grade 1 = Mild Adverse Event (AE), Grade 2 = Moderate AE, Grade 3 = Severe and Undesirable AE, Grade 4 = Life-threatening or Disabling AE, and Grade 5 = Death; Serious AEs (SAEs) are those that resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in an important medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes listed above. after the first dose of study drug and within 28 days after the last dose. A Treatment Emergent Adverse event (TEAE) is defined as any AE occurring or worsening on or after the first dose of study drug and within 28 days after the last dose of study drug.

Outcome measures

Outcome measures
Measure	Investigators Choice n=83 Participants Participants received a single agent investigators choice (IC) of chlorambucil 40 mg/m\^2 PO every 28 days until progressive disease (PD) or toxicity, OR rituximab 375 mg/m\^2 by intravenous (IV) infusion on days 1, 8, 15 and 22 of each 56-day treatment cycle until PD or toxicity, OR cytarabine 1-2 g/m\^2 by IV infusion on days 1 and 2 of each 28 day treatment cycle; up to 6 cycles, OR gemcitabine 1000 mg/m\^2 by IV infusion on days 1, 8 and 15 of each 28 day treatment cycle; up to 6 cycles OR oral fludarabine 40 mg/m\^2 or IV fludarabine 25 mg/m\^2 on days 1 through 5 of each 28-day cycle; up to 6 cycles. Participants were given the option to enter into the lenalidomide crossover phase if PD occurred and received lenalidomide 25 mg capsules daily on days 1 to 21 of each 28 day treatment cycle until PD or toxicity.	Lenalidomide n=167 Participants Participants received lenalidomide 25 mg capsules orally every day for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity. Participants with moderate renal insufficiency (creatinine clearance is ≥ 30 mL/min but \< 60mL/min received 10 mg lenalidomide for 21 days of each 28-day cycle (Cycles 1 and 2). After Cycle 2, if the participant remained free of Grade 3 or Grade 4 toxicity, the dose was increased to 15 mg lenalidomide for 21 days of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Number of Participants With Treatment Emergent Adverse Events TEAE Leading to Dose Interruption	28 Participants	110 Participants
Number of Participants With Treatment Emergent Adverse Events Related AE Leading to Dose Interruption	25 Participants	98 Participants
Number of Participants With Treatment Emergent Adverse Events TEAE Leading to Dose Reduction	13 Participants	72 Participants
Number of Participants With Treatment Emergent Adverse Events Any Serious Adverse Event (SAE)	22 Participants	75 Participants
Number of Participants With Treatment Emergent Adverse Events Any SAE Related to IP	12 Participants	38 Participants
Number of Participants With Treatment Emergent Adverse Events Any TEAE Leading to Stopping of IP	14 Participants	31 Participants
Number of Participants With Treatment Emergent Adverse Events Any Treatment Related AE Leading to Stopping IP	7 Participants	18 Participants
Number of Participants With Treatment Emergent Adverse Events TEAE Leading to Dose Reduction/Interruption	33 Participants	114 Participants
Number of Participants With Treatment Emergent Adverse Events Related AE Leading to Dose Reduction	10 Participants	69 Participants
Number of Participants With Treatment Emergent Adverse Events Related AE Leading to Dose Reduct/Interruption	29 Participants	103 Participants
Number of Participants With Treatment Emergent Adverse Events Any Grade 5 AE Related to IP	0 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events Any TEAE	69 Participants	159 Participants
Number of Participants With Treatment Emergent Adverse Events Any TEAE Grade 3 AE	49 Participants	126 Participants
Number of Participants With Treatment Emergent Adverse Events Any TEAE Grade 4 AE	29 Participants	56 Participants
Number of Participants With Treatment Emergent Adverse Events Any Grade 3 AE Related to IP	36 Participants	106 Participants
Number of Participants With Treatment Emergent Adverse Events Any Grade 4 AE Related to IP	19 Participants	46 Participants
Number of Participants With Treatment Emergent Adverse Events Any TEAE Grade 5 AE	2 Participants	15 Participants
Number of Participants With Treatment Emergent Adverse Events Any TEAE Related to the IP	51 Participants	141 Participants

SECONDARY outcome

Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.