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

A Phase 2, Multicenter, Randomized Open-Label Study To Determine the Efficacy of Lenalidomide (Revlimid®) Versus Investigator's Choice in Patients With Relapsed or Refractory Mantle Cell Lymphoma

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00875667

Acronym

Sprint

Enrollment

254

Registered

2009-04-03

Start date

2009-04-30

Completion date

2018-10-09

Last updated

2019-09-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lymphoma, Mantle-Cell, Mantle Cell Lymphoma

Keywords

Mantle Cell Lymphoma, Relapsed Mantle Cell Lymphoma, Refractory Mantle Cell Lymphoma, Lymphoma, MCL

Brief summary

To evaluate the safety and efficacy of lenalidomide versus investigator choice in patients with relapsed or refractory mantle cell lymphoma.

Detailed description

This research study is for patients who have relapsed or refractory mantle cell lymphoma following treatment such as radiotherapy, immunotherapy, chemotherapy, or radioimmunotherapy. Chemotherapy agents such as gemcitabine, cytarabine, chlorambucil, fludarabine, or the immunotherapeutic agent, rituximab, may be proposed. Thus, the aim is to search for new treatments that may improve the prognosis of patients with relapsed mantle cell lymphoma. The present clinical study aims at determining if lenalidomide is safe and active in patients with mantle cell lymphoma who are refractory to their treatment or have relapsed once, twice or three times. Enrollment goal was met on March 7th 2013 and thus enrollment was stopped.

Interventions

DRUGLenalidomide

For patients with a creatinine clearance of ≥ 60 mL/min: 25 mg daily x 21 days of a 28 day cycle until disease progression or unacceptable toxicity. For patients who have a moderate renal insufficiency (creatinine clearance is ≥ 30 mL/min but \< 60mL/min: 10 mg daily x 21 days of a 28 day cycle (Cycles 1 and 2). After Cycle 2, if the patient remains free of Grade 3 or Grade 4 toxicity, the dose will be increased to 15 mg daily x 21 days of a 28 day cycle until disease progression or unacceptable toxicity.

DRUGInvestigators choice single agent

Investigators choice single agent - Chlorambucil, Rituximab, Cytarabine, Gemcitabine, or Fludarabine

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Biopsy proven mantle cell lymphoma * Patients who are refractory to their regimen or have relapsed once, twice or up to three times and who have documented progressive disease * Eastern Cooperative Oncology Group (ECOG) performance score 0,1, or 2 * Willing to follow pregnancy precaution

Exclusion criteria

* Any of the following laboratory abnormalities * Absolute neutrophil count (ANC) \< 1,500 cells/mm\^3 (1.5 x 10\^9/L) * Platelet count \< 60,000/mm\^3 (60 x 10\^9/L) * Serum aspartate transaminase/serum glutamic oxaloacetic transaminase(AST/SGOT) or alanine transaminase/serum glutamic pyruvic transaminase (ALT/SGPT) \>3.0 x upper limit or normal (ULN), except patients with documented liver involvement by lymphoma * Serum total bilirubin \> 1.5 x ULN, except in case of Gilbert's Syndrome and documented liver involvement by lymphoma. * Calculated creatinine clearance (Cockcroft-Gault formula) of \< 30 mL/min * History of active central nervous system (CNS) lymphoma within the previous 3 months * Subjects not willing to take deep venous thrombosis (DVT) prophylaxis * Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are sero-positive because of hepatitis B virus vaccine are eligible

Design outcomes

Primary

Measure	Time frame	Description
Kaplan Meier Estimate for Progression Free Survival (PFS) by Independent Review Committee (IRC) Central Review	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	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.
Kaplan Meier Estimate for Progression Free Survival by Investigator's Assessment at the Final Analysis	From randomization to progression of disease or death; up to study discontinuation of 09 October 2018; overall median follow-up time was 285 weeks	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.

Secondary

Measure	Time frame	Description
Kaplan Meier Estimate for Duration of Response (DOR) According to the IRC Central Review	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	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.
Kaplan Meier Estimate for Duration of Response as Assessed by the Investigator at the Final Analysis	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	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.
Percentage of Participants With a Complete Response, Unconfirmed Complete Response, Partial Response and Stable Disease According to the IRC Central Review	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	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.
Percentage of Participants With a Complete Response, Unconfirmed Complete Response, Partial Response and Stable Disease at the Final Analysis	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	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.
Kaplan Meier Estimate of Time to Progression According to the IRC Central Review	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	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.
Kaplan Meier Estimate of Time to Progression as Assessed by the Investigator at the Final Analysis	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	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.
Kaplan Meier Estimate of Time to Treatment Failure (TTF) as Assessed by the Investigator	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	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.
Kaplan Meier Estimate of Time to Treatment Failure as Assessed by the Investigator at the Final Analysis	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	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.
Kaplan Meier Estimate of Time to First Response (TTFR) According to the IRC Central Review	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	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.
Kaplan Meier Estimate of Time to First Response as Assessed by the Investigator at the Final Analysis	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	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.
Kaplan Meier Estimate for Overall Survival (OS) According to the IRC Central Review	From date of randomization to the data cut-off date of 07 March 2014; overall median follow-up was 93.9 weeks	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.
Kaplan Meier Estimate for Overall Survival as Assessed by the Investigator at the Final Analysis	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	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.
Number of Participants With Treatment Emergent Adverse Events	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	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.
Mean Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain	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.	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Physical Functioning Scale ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Maximum Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain to Treatment Discontinuation Visit	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.	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Physical Functioning Scale ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Mean Change From Baseline in the EORTC QLQ-C30 Role Functioning Domain	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.	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Role Functioning Scale ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Maximum Change From Baseline in the EORTC QLQ-C30 Role Functioning Domain to Treatment Discontinuation Visit	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.	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Role Functioning Scale ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Mean Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Domain	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.	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Cognitive Functioning Domain ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Maximum Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Domain to Treatment Discontinuation Visit	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.	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Cognitive Functioning Scale ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Mean Change From Baseline in the EORTC QLQ-C30 Social Functioning Domain	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.	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Social Functioning Domain ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Maximum Change From Baseline in the EORTC QLQ-C30 Social Functioning Domain to Treatment Discontinuation Visit	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.	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Social Functioning Scale ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Mean Change From Baseline in the EORTC QLQ-C30 Fatigue Domain	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.	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Domain was scored between 0 and 100, with a higher score representing worse symptomatic expression.
Maximum Change From Baseline in the EORTC QLQ-C30 Fatigue Domain to Treatment Discontinuation Visit	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.	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale was scored between 0 and 100, with a higher score representing worse symptomatic expression.
Mean Change From Baseline in the EORTC QLQ-C30 Pain Domain	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.	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Pain Domain was scored between 0 and 100, with a higher score representing worse symptomatic expression.
Maximum Change From Baseline in the EORTC QLQ-C30 Pain Domain to Treatment Discontinuation Visit	Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and time of discontinuation from treatment visit.Up to final data cut-0ff date of 07 March 2014	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Pain Scale was scored between 0 and 100, with a higher score representing worse symptomatic expression.
Mean Change From Baseline in the EORTC QLQ-C30 Nausea / Vomiting Domain	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.	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Nausea and Vomiting Domain was scored between 0 and 100, with a higher score representing worse symptomatic expression.
Maximum Change From Baseline in the EORTC QLQ-C30 Nausea and Vomiting Domain to Treatment Discontinuation Visit	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.	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Nausea and Vomiting Scale was scored between 0 and 100, with a high score representing worse symptomatic expression.
Mean Change From Baseline in the EORTC QLQ-C30 Constipation	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.	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Constipation Domain was scored between 0 and 100, with a high score representing worse symptomatic expression.
Maximum Change From Baseline in the EORTC QLQ-C30 Constipation Domain to Treatment Discontinuation Visit	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.	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Constipation Scale was scored between 0 and 100, with a higher score representing worse symptomatic expression.
Mean Change From Baseline in the EORTC QLQ-C30 Diarhoea	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.	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Diarhoea Domain was scored between 0 and 100, with a higher score representing worse symptomatic expression.
Maximum Change From Baseline in the EORTC QLQ-C30 Diarhoea Domain to Treatment Discontinuation Visit	Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and time of discontinuation from treatment visit.Up to final data cut-0ff date of 07 March 2014	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Diarhoea Scale was scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Mean Change From Baseline in the EORTC QLQ-C30 Insomnia Domain	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.	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Insomnia Domain was scored between 0 and 100, with a higher score representing worse symptomatic expression.
Maximum Change From Baseline in the EORTC QLQ-C30 Insomnia Domain to Treatment Discontinuation Visit	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.	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Insomnia Scale was scored between 0 and 100, with a high score representing worse symptomatic expression.
Mean Change From Baseline in the EORTC QLQ-C30 Dyspnoea Domain to Treatment Discontinuation Visit	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.	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnoea Domain was scored between 0 and 100, with a high score representing worse symptomatic expression.
Maximum Change From Baseline in the EORTC QLQ-C30 Dyspnoea Domain to Treatment Discontinuation Visit	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.	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnoea Domain to Treatment Scale was scored between 0 and 100, with a higher score representing worse symptomatic expression.
Mean Change From Baseline in the EORTC QLQ-C30 Appetite Loss Domain to Treatment Discontinuation Visit	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.	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Appetite Loss Domain was scored between 0 and 100, with a higher score representing worse symptomatic expression.
Maximum Change From Baseline in the EORTC QLQ-C30 Appetite Loss Domain to Treatment Discontinuation Visit	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.	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Appetite Loss Domain to Treatment Scale was scored between 0 and 100, with a higher score representing worse symptomatic expression.
Mean Change From Baseline in the EORTC QLQ-C30 Financial Problems Domain to Treatment Discontinuation Visit	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.	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Financial Problems Domain was scored between 0 and 100, with a higher score representing worse symptomatic expression.
Maximum Change From Baseline in the EORTC QLQ-C30 Financial Problems Domain to Treatment Discontinuation Visit	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.	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Financial Problems Domain Scale was scored between 0 and 100, with a higher score representing worse symptomatic expression.
Percentage of Participants Who Achieved an Overall Response According to the IRC Central Review	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	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.
Maximum Change From Baseline in the EORTC QLQ-C30 Global Health Status / QoL Domain to Treatment Discontinuation Visit	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.	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status / QoL Domain to Treatment Scale was scored between 0 and 100, with a higher score representing a higher quality of life.
Mean Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain	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.	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Emotional Domain ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Maximum Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain to Treatment Discontinuation Visit	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.	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Emotional Functioning Scale ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Mean Change From Baseline in the EORTC QLQ-C30 Global Health Status / QoL Domain	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.	The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status / QoL Domain was scored between 0 and 100, with a higher score representing a higher quality of life.
Percentage of Participants Who Achieved an Overall Response as Assessed by the Investigator at the Final Analysis	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	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.

Countries

Belgium, Czechia, Denmark, France, Germany, Greece, Israel, Italy, Netherlands, Poland, Russia, Spain, Sweden, United Kingdom

Participant flow

Recruitment details

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).

Pre-assignment details

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.

Participants by arm

Arm	Count
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.	170
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.	84
Total	254

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	29	10
Overall Study	Death	7	2
Overall Study	Disease Progression	100	49
Overall Study	Miscellaneous	12	6
Overall Study	Protocol Violation	2	0
Overall Study	Randomized but no Study Drug Given	3	1
Overall Study	Withdrawal by Subject	17	5

Baseline characteristics

Characteristic	Lenalidomide	Investigators Choice	Total
Age, Continuous	68.0 Years STANDARD_DEVIATION 9.38	67.5 Years STANDARD_DEVIATION 8.2	67.8 Years STANDARD_DEVIATION 9
Bone Marrow Involvment as Baseline Intermediate	4 Participants	3 Participants	7 Participants
Bone Marrow Involvment as Baseline Missing	118 Participants	57 Participants	175 Participants
Bone Marrow Involvment as Baseline Negative	27 Participants	11 Participants	38 Participants
Bone Marrow Involvment as Baseline Positive	21 Participants	13 Participants	34 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 = Fully Active	65 Participants	36 Participants	101 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1 = Restrictive but Ambulatory	77 Participants	37 Participants	114 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2 = Ambulatory but Unable to Work	27 Participants	11 Participants	38 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 3 = Limited Self-Care	0 Participants	0 Participants	0 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Missing	1 Participants	0 Participants	1 Participants
MCL International Prognostic Index (MIPI) Score at Baseline High Risk	60 Participants	25 Participants	85 Participants
MCL International Prognostic Index (MIPI) Score at Baseline Intermediate Risk	66 Participants	37 Participants	103 Participants
MCL International Prognostic Index (MIPI) Score at Baseline Low Risk	42 Participants	21 Participants	63 Participants
MCL International Prognostic Index (MIPI) Score at Baseline Missing	2 Participants	1 Participants	3 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	9 Participants	4 Participants	13 Participants
Race (NIH/OMB) White	161 Participants	80 Participants	241 Participants
Sex: Female, Male Female	47 Participants	21 Participants	68 Participants
Sex: Female, Male Male	123 Participants	63 Participants	186 Participants
Stage of Mantle Cell Lymphoma (MCL) at Diagnosis Missing	4 Participants	2 Participants	6 Participants
Stage of Mantle Cell Lymphoma (MCL) at Diagnosis Stage I	3 Participants	2 Participants	5 Participants
Stage of Mantle Cell Lymphoma (MCL) at Diagnosis Stage II	10 Participants	1 Participants	11 Participants
Stage of Mantle Cell Lymphoma (MCL) at Diagnosis Stage III	30 Participants	20 Participants	50 Participants
Stage of Mantle Cell Lymphoma (MCL) at Diagnosis Stage IV	123 Participants	59 Participants	182 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	119 / 167	59 / 83
other Total, other adverse events	146 / 167	61 / 83
serious Total, serious adverse events	75 / 167	22 / 83

Outcome results

Primary

Kaplan Meier Estimate for Progression Free Survival by Investigator's Assessment at the Final Analysis

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.

Time frame: 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.

Arm	Measure	Value (MEDIAN)
Lenalidomide	Kaplan Meier Estimate for Progression Free Survival by Investigator's Assessment at the Final Analysis	37.3 weeks
Investigators Choice	Kaplan Meier Estimate for Progression Free Survival by Investigator's Assessment at the Final Analysis	23.6 weeks

p-value: 0.00395% CI: [0.43, 0.85]Stratified Log Rank Test

Primary

Kaplan Meier Estimate for Progression Free Survival (PFS) by Independent Review Committee (IRC) Central Review

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.

Time frame: 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.

Arm	Measure	Value (MEDIAN)
Lenalidomide	Kaplan Meier Estimate for Progression Free Survival (PFS) by Independent Review Committee (IRC) Central Review	37.6 weeks
Investigators Choice	Kaplan Meier Estimate for Progression Free Survival (PFS) by Independent Review Committee (IRC) Central Review	22.7 weeks

p-value: 0.01295% CI: [0.43, 0.9]Stratified Log Rank Test

Secondary

Kaplan Meier Estimate for Duration of Response as Assessed by the Investigator at the Final Analysis

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.

Time frame: 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.

Arm	Measure	Value (MEDIAN)
Lenalidomide	Kaplan Meier Estimate for Duration of Response as Assessed by the Investigator at the Final Analysis	70.1 Weeks
Investigators Choice	Kaplan Meier Estimate for Duration of Response as Assessed by the Investigator at the Final Analysis	91.7 Weeks

p-value: 0.87595% CI: [0.52, 1.74]Log Rank

Secondary

Kaplan Meier Estimate for Duration of Response (DOR) According to the IRC Central Review

Time frame: 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.

Arm	Measure	Value (MEDIAN)
Lenalidomide	Kaplan Meier Estimate for Duration of Response (DOR) According to the IRC Central Review	69.6 Weeks
Investigators Choice	Kaplan Meier Estimate for Duration of Response (DOR) According to the IRC Central Review	45.1 Weeks

p-value: 0.42195% CI: [0.29, 1.68]Log Rank

Secondary

Kaplan Meier Estimate for Overall Survival as Assessed by the Investigator at the Final Analysis

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.

Time frame: 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.

Arm	Measure	Value (MEDIAN)
Lenalidomide	Kaplan Meier Estimate for Overall Survival as Assessed by the Investigator at the Final Analysis	120.6 weeks
Investigators Choice	Kaplan Meier Estimate for Overall Survival as Assessed by the Investigator at the Final Analysis	91.7 weeks

p-value: 0.55895% CI: [0.67, 1.25]Log Rank

Secondary

Kaplan Meier Estimate for Overall Survival (OS) According to the IRC Central Review

Time frame: 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.

Arm	Measure	Value (MEDIAN)
Lenalidomide	Kaplan Meier Estimate for Overall Survival (OS) According to the IRC Central Review	121.0 weeks
Investigators Choice	Kaplan Meier Estimate for Overall Survival (OS) According to the IRC Central Review	91.7 weeks

p-value: 0.51995% CI: [0.62, 1.28]Log Rank

Secondary

Kaplan Meier Estimate of Time to First Response as Assessed by the Investigator at the Final Analysis

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.

Time frame: 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.

Arm	Measure	Value (MEDIAN)
Lenalidomide	Kaplan Meier Estimate of Time to First Response as Assessed by the Investigator at the Final Analysis	23.9 Weeks
Investigators Choice	Kaplan Meier Estimate of Time to First Response as Assessed by the Investigator at the Final Analysis	40.0 Weeks

p-value: <0.00495% CI: [1.24, 3.42]Log Rank

Secondary

Kaplan Meier Estimate of Time to First Response (TTFR) According to the IRC Central Review

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.

Time frame: 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.

Arm	Measure	Value (MEDIAN)
Lenalidomide	Kaplan Meier Estimate of Time to First Response (TTFR) According to the IRC Central Review	18.7 Weeks
Investigators Choice	Kaplan Meier Estimate of Time to First Response (TTFR) According to the IRC Central Review	NA Weeks

p-value: <0.00195% CI: [1.95, 7.85]Log Rank

Secondary

Kaplan Meier Estimate of Time to Progression According to the IRC Central Review

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.

Time frame: 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.

Arm	Measure	Value (MEDIAN)
Lenalidomide	Kaplan Meier Estimate of Time to Progression According to the IRC Central Review	39.3 Weeks
Investigators Choice	Kaplan Meier Estimate of Time to Progression According to the IRC Central Review	24.7 Weeks

p-value: 0.00595% CI: [0.45, 0.87]Log Rank

Secondary

Kaplan Meier Estimate of Time to Progression as Assessed by the Investigator at the Final Analysis

Time frame: 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.

Arm	Measure	Value (MEDIAN)
Lenalidomide	Kaplan Meier Estimate of Time to Progression as Assessed by the Investigator at the Final Analysis	39.3 Weeks
Investigators Choice	Kaplan Meier Estimate of Time to Progression as Assessed by the Investigator at the Final Analysis	24.7 Weeks

p-value: 0.00395% CI: [0.46, 0.86]Log Rank

Secondary

Kaplan Meier Estimate of Time to Treatment Failure as Assessed by the Investigator at the Final Analysis

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.

Time frame: 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.

Arm	Measure	Value (MEDIAN)
Lenalidomide	Kaplan Meier Estimate of Time to Treatment Failure as Assessed by the Investigator at the Final Analysis	24.4 weeks
Investigators Choice	Kaplan Meier Estimate of Time to Treatment Failure as Assessed by the Investigator at the Final Analysis	17.9 weeks

p-value: 0.09595% CI: [0.58, 1.05]Log Rank

Secondary

Kaplan Meier Estimate of Time to Treatment Failure (TTF) as Assessed by the Investigator

Time frame: 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.

Arm	Measure	Value (MEDIAN)
Lenalidomide	Kaplan Meier Estimate of Time to Treatment Failure (TTF) as Assessed by the Investigator	24.4 weeks
Investigators Choice	Kaplan Meier Estimate of Time to Treatment Failure (TTF) as Assessed by the Investigator	17.9 weeks

p-value: 0.04695% CI: [0.54, 1]Log Rank

Secondary

Maximum Change From Baseline in the EORTC QLQ-C30 Appetite Loss Domain to Treatment Discontinuation Visit

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Appetite Loss Domain to Treatment Scale was scored between 0 and 100, with a higher score representing worse symptomatic expression.

Time frame: 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.