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

• Sponsor: Celgene (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00875667
• Collaborator: (none)
• Enrollment: 254
• Locations: 97
• Arms: 2
• Actual Duration (Months): 113.3
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Mantle Cell Lymphoma; Lymphoma, Mantle-Cell	Drug: Lenalidomide; Drug: Investigators choice single agent	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 254 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Apr 30, 2009
• Actual Primary Completion Date: Jun 28, 2018
• Actual Study Completion Date: Oct 9, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lenalidomide Lenalidomide	Drug: Lenalidomide; 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.; Other Names: Revlimid Rev CC-5013
Active Comparator: Investigators choice single agent Investigators choice single agent - Chlorambucil, Rituximab, Cytarabine, Gemcitabine, Fludarabine	Drug: Investigators choice single agent; Investigators choice single agent - Chlorambucil, Rituximab, Cytarabine, Gemcitabine, or Fludarabine; Other Names: Leukeran Ritux Rituxan cytosine arabinoside Ara-C Cytosar-U Gemzar fludarabine phosphate Fludara

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

21. 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.

22. 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.

23. 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.

24. 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.

25. 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.

26. 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.

27. 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.

28. 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.

29. 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.

30. 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.

31. 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.

32. 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.

33. 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.

34. 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.

35. 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.

36. 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.

37. 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.

38. 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.

39. 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.

40. 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.

41. 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.

42. 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.

43. 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.

44. 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.

45. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UZ Brussels	Brussel		Belgium	1090
2	UZ Gent	Gent		Belgium	9000
3	AZ Groeninge	Kortrijk		Belgium	8500
4	Cliniques Universitaires UCL de Mont-Godine	Yvoir		Belgium	5530
5	Teaching Hospital BrnoHemato-oncology Dept	Brno		Czechia	625 00
6	University Hospital2.Dep. of Int.med. hematology	Hradec Kralove		Czechia	500 05
7	Charles University General Hospital	Prague		Czechia	12808
8	Rigshospitalet Department of Haematology L4042	Copenhagen		Denmark	2100
9	Herlev Hospital	Herlev		Denmark	2730
10	Polyclinique Bordeaux Nord Aquitaine Service Onco-Hematologie	Bordeaux		France	33300
11	Hotel Dieu	Clermont Ferrand		France	63003
12	CHU Hopital Michallon	Grenoble cedex 09		France	38043
13	Centre Hospitalier Departemental Les Oudrairies	La Roche sur Yon		France	85025
14	Clinique Victor Hugo	Le Mans		France	72000
15	CHRU-Hopital Claude Huriez	Lille		France	59037
16	CHU Dupuytren	Limoges Cedex 1		France	87042
17	Centre Leon Berard	Lyon		France	69373
18	Institut Paoli-Calmettes	Marseille		France	13273
19	CHU Montpellier - Hôpital Saint Eloi	Montpellier CEDEX 5		France	34295
20	CHRU - Hotel Dieu	Nantes Cedex 1		France	44093
21	Centre Antoine Lacassagne Oncologie medicale et Hematologie	Nice cedex 1		France	06050
22	Hopital Saint-Louis	Paris		France	75010
23	CHRU - Hopital du Haut Leveque	Pessac		France	33604
24	Centre Hospitalier Lyon Sud	Pierre-Bénite cedex		France	69495
25	CHU Rennes Hematology	Rennes		France	35033
26	Centre Henri Becquerel	Rouen Cedex		France	79038
27	Hopital civil	Strasbourg		France	67091
28	CHRU Hôpital de Hautepierre	Strasbourg		France	67098
29	CHRU Hopitaux de Brabois	Vandoeuvre		France	54511
30	Universitatsklinikum Essen	Essen		Germany	45122
31	Universitaetsklinikum FreiburgInnere Med.1, Haematologie	Freiburg		Germany	79106
32	UKG Universitatsklinikum Gottingen	Göttingen		Germany	37099
33	Asklepios Klinik St. Georg	Hamburg		Germany	D-20099
34	Universitatsklinikum des Saarlandes	Homburg-Saar		Germany	66421
35	Stadtisches Klinikum Karlsruhe	Karlsruhe		Germany	76135
36	Uniklinik Koln	Koeln		Germany	50937
37	Universitatsklinik Munster	Muenster		Germany	48129
38	University of Ulm	Ulm		Germany	89081
39	Attikon General University Hospital of Athens	Athens		Greece	12462
40	University of Patras	Patras		Greece	26500
41	Rambam Medical Center	Haifa		Israel	35254
42	Hadassah University Hospital	Jerusalem		Israel	91120
43	Rabin Medical Center	Petach-Tikva		Israel	49100
44	Sheba Medical Center	Tel Hashomer		Israel	52621
45	A.O. Policlinico - Università di Bari	Bari		Italy	70124
46	A.O.U. di Bologna Policlinico S.Orsola-Malpighi	Bologna		Italy	40138
47	Ospedale Regionale di Bolzano	Bolzano		Italy	39100
48	Ospedale Ferrarotto	Catania		Italy	95124
49	Azienda Ospedaliera Universitaria San Martino	Genova		Italy	16132
50	Ematologia ed Immunologia	Lecce		Italy	73100
51	Istituto Europeo di Oncologia - IEO	Milano		Italy	20141
52	San Raffaele Scientific Institute	Milano		Italy	20932
53	Az. Osp. Vincenzo Cervello	Palermo		Italy	90146
54	I.R.C.C.S. Policlinico San Matteo	Pavia		Italy	27100
55	Az. Osp di Perugia	Perugia		Italy	06100
56	Ospedale S. Chiara	Pisa		Italy	56126
57	Azienda Ospedaliera "Bianchi-Melacrino-Morelli"	Reggio Calabria		Italy	89100
58	Reference Cancer Center of Basilicata	Rionero in Vulture		Italy	85028
59	IRCCS Casa Sollievo della Sofferenza	San Giovanni Rotondo		Italy	71013
60	Meander Medisch Centrum	Amersfoort		Netherlands	3818 ES
61	Medisch Spectrum Twente	Enshede		Netherlands	7513
62	Isala Klinieken	Zwolle		Netherlands	8011
63	Uniwersytet Jagiellonski Collegium Medicum	Krakow		Poland	31-501
64	Malopolskie Centrum medyczne s.c.	Kraków		Poland	30-510
65	Wojewodzki Szpital Specjalistyczny im. M. Kopernika w Lodzi	Lodz		Poland	93-510
66	Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie w Warszawie	Warsaw		Poland	02-781
67	Nowotworww Krwi i Transplantacji Szpiku	Wroclaw		Poland	50-367
68	Dolnoslaskie Centrum Transplantacji Komorkowych	Wroclaw		Poland	53-439
69	Sverdlovsk Regional Clinical Hospital 1	Ekaterinburg		Russian Federation	620102
70	Republic Clinical Oncology Dispensary	Kazan		Russian Federation	420029
71	Institution of Russian Academy of Medical Sciences Russian Oncological Research Centre n.a. N. N. Bl	Moscow		Russian Federation	115447
72	Nizhegorodskiy Regional Clinical Hospital named after N.A. Semashko	Nizhniy Novgorod		Russian Federation	603126
73	Novosibirsk State Regional Clinical Hospital	Novosibirsk		Russian Federation	630087
74	Medical Radiology Research Centre RAMS	Obninsk		Russian Federation	249036
75	Perm Territorial Oncology Dispensary	Perm		Russian Federation	614066
76	Scientific Research Institute of OncologySoft Tissue Department	Rostov-na-Donu		Russian Federation	344937
77	St. Petersburg Research Institute of Hematology and Blood Transfusion	Saint-Petersburg		Russian Federation	191024
78	St. Petersburg Pavlov State Medical University	Saint-Petersburg		Russian Federation	196022
79	Saratov Medical University Chair of Professional Pathology and Haematology	Saratov		Russian Federation	410 028
80	Federal Centre of Heart, Blood and Endocrinology of Rosmed technlologies V.A. Almazov	St. Petersburg		Russian Federation	197341
81	Volgograd Regional Clinical Oncology Dispensary 1	Volgograd		Russian Federation	400138
82	Hospital Universitario Vall D Hebron	Barcelona		Spain	8035
83	Hospital de La Princesa	Madrid		Spain	28006
84	Hospital La Paz	Madrid		Spain	28046
85	Hospital Costa del Sol	Marbella		Spain	29603
86	Clinica Universitaria de Navarra	Pamplona		Spain	31008
87	Lund University Hosptial	Lund		Sweden	22185
88	University Hospital Uppsala	Uppsala		Sweden	75185
89	Royal Bournemouth Hosp	Bournemouth		United Kingdom	BH7 7DW
90	Addenbrookes Hospital	Cambridge		United Kingdom	CB2 0QQ
91	Royal Liverpool University Hospital	Liverpool		United Kingdom	L7 8XP
92	Christie Hospital	Manchester		United Kingdom	M20 4BX
93	Newcastle Hospital Foundation Trust	Newcastle Upon Tyne		United Kingdom	NE1 4LP
94	John Radcliffe Hospital	Oxford		United Kingdom	OX3 7LJ
95	Derriford Hospital	Plymouth		United Kingdom	PL6 8DH
96	Southampton General Hospital	Southampton		United Kingdom	SO16 6YD
97	The Royal Wolverhampton Hospital NHS Trust	Wolverhampton		United Kingdom	WV10 0QP

Sponsors and Collaborators

• Celgene

Investigators

• Principal Investigator: Marek Trneny, MD/PhD/Prof, Head, Ist Dept Medicine, Charles University Hospital; Director, Institute of Hematology and Blood Transfusion; Chair, Czech Lymphoma Study Group

Study Documents (Full-Text)

• Study Protocol - May 31, 2018
• Statistical Analysis Plan: CC-5013-MCL-002_SAP_Final_Redacted.19 December 2012 - Dec 19, 2012
• Statistical Analysis Plan: CC05013-MCL-002_SAP_2011_Redacted 18 July 2011 - Jul 18, 2011
• Statistical Analysis Plan: CC-5013-MCL-002_SAP_2010_Redacted 26 July 2010 - Jul 26, 2010

More Information

Publications

• Trněný M, Lamy T, Walewski J, Belada D, Mayer J, Radford J, Jurczak W, Morschhauser F, Alexeeva J, Rule S, Afanasyev B, Kaplanov K, Thyss A, Kuzmin A, Voloshin S, Kuliczkowski K, Giza A, Milpied N, Stelitano C, Marks R, Trümper L, Biyukov T, Patturajan M, Bravo MC, Arcaini L; SPRINT trial investigators and in collaboration with the European Mantle Cell Lymphoma Network. Lenalidomide versus investigator's choice in relapsed or refractory mantle cell lymphoma (MCL-002; SPRINT): a phase 2, randomised, multicentre trial. Lancet Oncol. 2016 Mar;17(3):319-331. doi: 10.1016/S1470-2045(15)00559-8. Epub 2016 Feb 16.

• Responsible Party: Celgene
• ClinicalTrials.gov Identifier: NCT00875667
• Other Study ID Numbers: CC-5013-MCL-002
• First Posted: Apr 3, 2009
• Last Update Posted: Sep 16, 2019
• Last Verified: Aug 1, 2019

• Keywords provided by Celgene: Mantle Cell Lymphoma; Relapsed Mantle Cell Lymphoma; Refractory Mantle Cell Lymphoma; Lymphoma; MCL
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Mantle-Cell; Fludarabine; Fludarabine phosphate; Lenalidomide

Study Results

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 Detail	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.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	170	84
Crossover From IC to Lenalidomide	0	40
Participants Treated	167	83
COMPLETED	0	11
NOT COMPLETED	170	73

Baseline Characteristics

Arm/Group Title	Lenalidomide	Investigators Choice	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	170	84	254
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	68.0 (9.38)	67.5 (8.20)	67.8 (9.00)
Sex: Female, Male (Count of Participants)
Female	47 27.6%	21 25%	68 26.8%
Male	123 72.4%	63 75%	186 73.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	161 94.7%	80 95.2%	241 94.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	9 5.3%	4 4.8%	13 5.1%
Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of Participants)
0 = Fully Active	65 38.2%	36 42.9%	101 39.8%
1 = Restrictive but Ambulatory	77 45.3%	37 44%	114 44.9%
2 = Ambulatory but Unable to Work	27 15.9%	11 13.1%	38 15%
3 = Limited Self-Care	0 0%	0 0%	0 0%
Missing	1 0.6%	0 0%	1 0.4%
Stage of Mantle Cell Lymphoma (MCL) at Diagnosis (Count of Participants)
Stage I	3 1.8%	2 2.4%	5 2%
Stage II	10 5.9%	1 1.2%	11 4.3%
Stage III	30 17.6%	20 23.8%	50 19.7%
Stage IV	123 72.4%	59 70.2%	182 71.7%
Missing	4 2.4%	2 2.4%	6 2.4%
MCL International Prognostic Index (MIPI) Score at Baseline (Count of Participants)
Low Risk	42 24.7%	21 25%	63 24.8%
Intermediate Risk	66 38.8%	37 44%	103 40.6%
High Risk	60 35.3%	25 29.8%	85 33.5%
Missing	2 1.2%	1 1.2%	3 1.2%
Bone Marrow Involvment as Baseline (Count of Participants)
Negative	27 15.9%	11 13.1%	38 15%
Intermediate	4 2.4%	3 3.6%	7 2.8%
Positive	21 12.4%	13 15.5%	34 13.4%
Missing	118 69.4%	57 67.9%	175 68.9%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	170	84
Median (95% Confidence Interval) [weeks]	37.6	22.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Investigators Choice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments	Stratification factors were: time from diagnosis to first dose, time from last prior anti-lymphoma therapy to first dose, prior stem cell transplant, and MIPI at baseline
	Method	Stratified Log Rank Test
	Comments
Method of Estimation	Estimation Parameter	Stratified Hazard Ratio
	Estimated Value	0.63
	Confidence Interval	(2-Sided) 95%; 0.43 to 0.90
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	170	84
Median (95% Confidence Interval) [weeks]	37.3	23.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Investigators Choice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments	Stratification factors were: time from diagnosis to first dose, time from last prior anti-lymphoma therapy to first dose, prior stem cell transplant, and MIPI at baseline
	Method	Stratified Log Rank Test
	Comments
Method of Estimation	Estimation Parameter	Stratified Hazard Ratio
	Estimated Value	0.60
	Confidence Interval	(2-Sided) 95%; 0.43 to 0.85
	Parameter Dispersion	Type: Value:
	Estimation Comments	The weights are based on observed events at the time the third DMC meeting was held and based on the difference between observed and expected events at the time of the primary analysis.

3. Secondary Outcome

Title	Percentage of Participants Who Achieved an Overall Response According to the IRC Central Review
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	170	84
Number (95% Confidence Interval) [Percentage of Participants]	40.0 23.5%	10.7 12.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Investigators Choice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Chi-squared
	Comments

4. Secondary Outcome

Title	Percentage of Participants Who Achieved an Overall Response as Assessed by the Investigator at the Final Analysis
Description	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.
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

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	170	84
Number (95% Confidence Interval) [Percentage of Participants]	45.9 27%	22.6 26.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Investigators Choice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Chi-squared
	Comments

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The analysis population included participants with an overall response.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	68	9
Median (95% Confidence Interval) [Weeks]	69.6	45.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Investigators Choice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.421
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.70
	Confidence Interval	(2-Sided) 95%; 0.29 to 1.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The analysis population included participants with an overall response.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	78	19
Median (95% Confidence Interval) [Weeks]	70.1	91.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Investigators Choice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.875
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95%; 0.52 to 1.74
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Percentage of Participants With a Complete Response, Unconfirmed Complete Response, Partial Response and Stable Disease According to the IRC Central Review
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

ITT population includes all randomized participants.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	170	84
Number (95% Confidence Interval) [Percentage of Participants]	69.4 40.8%	63.1 75.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Investigators Choice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.313
	Comments
	Method	Chi-squared
	Comments

8. Secondary Outcome

Title	Percentage of Participants With a Complete Response, Unconfirmed Complete Response, Partial Response and Stable Disease at the Final Analysis
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

ITT population includes all randomized participants.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	170	84
Number (95% Confidence Interval) [Percentage of participants]	70.0 41.2%	65.5 78%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Investigators Choice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.465
	Comments
	Method	Chi-squared
	Comments

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT population includes all randomized participants.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	170	84
Median (95% Confidence Interval) [Weeks]	39.3	24.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Investigators Choice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.62
	Confidence Interval	(2-Sided) 95%; 0.45 to 0.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT population includes all randomized participants.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	170	84
Median (95% Confidence Interval) [Weeks]	39.3	24.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Investigators Choice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.63
	Confidence Interval	(2-Sided) 95%; 0.46 to 0.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Includes all treated participants.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	167	83
Median (95% Confidence Interval) [weeks]	24.4	17.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Investigators Choice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.046
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.74
	Confidence Interval	(2-Sided) 95%; 0.54 to 1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Includes all treated participants.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	167	83
Median (95% Confidence Interval) [weeks]	24.4	17.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Investigators Choice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.095
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.78
	Confidence Interval	(2-Sided) 95%; 0.58 to 1.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT population includes all randomized participants.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	170	84
Median (95% Confidence Interval) [Weeks]	18.7	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Investigators Choice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	3.91
	Confidence Interval	(2-Sided) 95%; 1.95 to 7.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT population includes all randomized participants.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	170	84
Median (95% Confidence Interval) [Weeks]	23.9	40.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Investigators Choice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.004
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.06
	Confidence Interval	(2-Sided) 95%; 1.24 to 3.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Kaplan Meier Estimate for Overall Survival (OS) According to the IRC Central Review
Description	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 date of randomization to the data cut-off date of 07 March 2014; overall median follow-up was 93.9 weeks

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	170	84
Median (95% Confidence Interval) [weeks]	121.0	91.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Investigators Choice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.519
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.62 to 1.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	170	84
Median (95% Confidence Interval) [weeks]	120.6	91.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Investigators Choice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.558
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95%; 0.67 to 1.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	167	83
Any TEAE	159 93.5%	69 82.1%
Any TEAE Grade 3 AE	126 74.1%	49 58.3%
Any TEAE Grade 4 AE	56 32.9%	29 34.5%
Any TEAE Grade 5 AE	15 8.8%	2 2.4%
Any TEAE Related to the IP	141 82.9%	51 60.7%
Any Grade 3 AE Related to IP	106 62.4%	36 42.9%
Any Grade 4 AE Related to IP	46 27.1%	19 22.6%
Any Grade 5 AE Related to IP	0 0%	0 0%
Any Serious Adverse Event (SAE)	75 44.1%	22 26.2%
Any SAE Related to IP	38 22.4%	12 14.3%
Any TEAE Leading to Stopping of IP	31 18.2%	14 16.7%
Any Treatment Related AE Leading to Stopping IP	18 10.6%	7 8.3%
TEAE Leading to Dose Reduction/Interruption	114 67.1%	33 39.3%
Related AE Leading to Dose Reduct/Interruption	103 60.6%	29 34.5%
TEAE Leading to Dose Reduction	72 42.4%	13 15.5%
Related AE Leading to Dose Reduction	69 40.6%	10 11.9%
TEAE Leading to Dose Interruption	110 64.7%	28 33.3%
Related AE Leading to Dose Interruption	98 57.6%	25 29.8%

18. Secondary Outcome

Title	Mean Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	160	74
Baseline	71.8 (22.35)	78.9 (17.38)
Change from Baseline to Cycle 3 Day 1	-0.5 (15.47)	-3.7 (16.22)
Change from Baseline to Cycle 5 Day 1	1.6 (15.18)	-2.1 (19.02)
Change from Baseline to Cycle 7 Day 1	2.4 (16.74)	4.2 (16.69)
Change from Baseline to Cycle 9 Day 1	2.8 (18.08)	11.1 (11.67)
Change from Baseline to Treatment Discontinuation	-5.6 (19.46)	-5.1 (17.14)

19. Secondary Outcome

Title	Maximum Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain to Treatment Discontinuation Visit
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	124	57
Mean (Standard Deviation) [units on a scale]	3.4 (18.70)	-1.8 (17.57)

20. Secondary Outcome

Title	Mean Change From Baseline in the EORTC QLQ-C30 Role Functioning Domain
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	161	74
Baseline	71.5 (31.10)	73.9 (25.60)
Change from Baseline to Cycle 3 Day 1	-4.8 (26.12)	3.5 (21.69)
Change from Baseline to Cycle 5 Day 1	1.4 (26.09)	-6.4 (30.21)
Change from Baseline to Cycle 7 Day 1	0.3 (26.44)	0.0 (38.83)
Change from Baseline to Cycle 9 Day 1	1.8 (26.75)	13.9 (19.48)
Change from Baseline to Treatment Discontinuation	-9.1 (29.05)	-4.3 (31.09)

21. Secondary Outcome

Title	Maximum Change From Baseline in the EORTC QLQ-C30 Role Functioning Domain to Treatment Discontinuation Visit
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	160	74
Mean (Standard Deviation) [units on a scale]	3.1 (28.43)	5.0 (27.09)

22. Secondary Outcome

Title	Mean Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Domain
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	161	74
Baseline	84.6 (19.86)	83.6 (20.18)
Change from Baseline to Cycle 3 Day 1	0.0 (16.34)	-2.3 (13.89)
Change from Baseline to Cycle 5 Day 1	-1.9 (17.72)	1.3 (14.85)
Change from Baseline to Cycle 7 Day 1	-3.2 (19.27)	4.2 (14.77)
Change from Baseline to Cycle 9 Day 1	-2.5 (18.05)	5.6 (13.61)
Change from Baseline to Treatment Discontinuation	-5.1 (19.46)	-2.3 (15.68)

23. Secondary Outcome

Title	Maximum Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Domain to Treatment Discontinuation Visit
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	160	74
Mean (Standard Deviation) [units on a scale]	3.2 (17.92)	2.9 (14.13)

24. Secondary Outcome

Title	Mean Change From Baseline in the EORTC QLQ-C30 Social Functioning Domain
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	161	74
Baseline	74.9 (28.39)	78.4 (26.85)
Change from Baseline to Cycle 3 Day 1	-1.0 (20.39)	-1.2 (22.54)
Change from Baseline to Cycle 5 Day 1	1.6 (19.75)	-4.5 (29.27)
Change from Baseline to Cycle 7 Day 1	-1.5 (25.06)	2.1 (28.78)
Change from Baseline to Cycle 9 Day 1	4.3 (22.11)	0.0 (23.57)
Change from Baseline to Treatment Discontinuation	-5.1 (24.63)	-2.7 (20.87)

25. Secondary Outcome

Title	Maximum Change From Baseline in the EORTC QLQ-C30 Social Functioning Domain to Treatment Discontinuation Visit
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	161	74
Mean (Standard Deviation) [units on a scale]	5.1 (20.87)	3.8 (19.92)

26. Secondary Outcome

Title	Mean Change From Baseline in the EORTC QLQ-C30 Fatigue Domain
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	161	74
Baseline	40.2 (26.67)	39.2 (23.50)
Change from Baseline to Cycle 3 Day 1	0.1 (21.72)	2.1 (22.12)
Change from Baseline to Cycle 5 Day 1	-3.2 (20.84)	3.4 (25.68)
Change from Baseline to Cycle 7 Day 1	-1.0 (21.03)	-6.9 (25.85)
Change from Baseline to Cycle 9 Day 1	-3.9 (26.64)	-7.4 (25.01)
Change from Baseline to Treatment Discontinuation	5.2 (21.48)	2.6 (24.11)

27. Secondary Outcome

Title	Maximum Change From Baseline in the EORTC QLQ-C30 Fatigue Domain to Treatment Discontinuation Visit
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	160	74
Mean (Standard Deviation) [units on a scale]	-4.9 (22.76)	-2.9 (23.24)

28. Secondary Outcome

Title	Mean Change From Baseline in the EORTC QLQ-C30 Pain Domain
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	160	74
Baseline	22.6 (25.86)	13.7 (20.15)
Cycle 3 Day 1	-2.2 (19.99)	-1.2 (25.30)
Cycle 5 Day 1	-0.2 (24.82)	-2.6 (20.38)
Cycle 7 Day 1	3.2 (26.99)	0.0 (19.92)
Cycle 9 Day 1	-3.2 (25.92)	-2.8 (6.80)
Treatment Discontinuation	4.6 (26.38)	3.5 (22.29)

29. Secondary Outcome

Title	Maximum Change From Baseline in the EORTC QLQ-C30 Pain Domain to Treatment Discontinuation Visit
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	160	74
Mean (Standard Deviation) [units on a scale]	-5.8 (24.61)	-3.5 (21.30)

30. Secondary Outcome

Title	Mean Change From Baseline in the EORTC QLQ-C30 Nausea / Vomiting Domain
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	161	74
Baseline	4.9 (10.31)	3.8 (11.22)
Change from Baseline to Cycle 3 Day 1	2.5 (14.39)	0.4 (10.60)
Change from Baseline to Cycle 5 Day 1	2.6 (11.83)	5.8 (21.57)
Change from Baseline to Cycle 7 Day 1	5.3 (17.30)	2.1 (22.60)
Change from Baseline to Cycle 9 Day 1	-0.7 (10.40)	2.8 (6.80)
Change from Baseline to Treatment Discontinuation	0.5 (9.99)	6.6 (18.59)

31. Secondary Outcome

Title	Maximum Change From Baseline in the EORTC QLQ-C30 Nausea and Vomiting Domain to Treatment Discontinuation Visit
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	161	74
Mean (Standard Deviation) [units on a scale]	-2.3 (8.82)	-0.6 (8.31)

32. Secondary Outcome

Title	Mean Change From Baseline in the EORTC QLQ-C30 Constipation
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	160	74
Baseline	12.5 (23.27)	8.6 (19.16)
Change from Baseline to Cycle 3 Day 1	6.3 (27.38)	-0.8 (18.53)
Change from Baseline to Cycle 5 Day 1	4.2 (25.78)	1.3 (17.59)
Change from Baseline to Cycle 7 Day 1	3.5 (27.95)	0.0 (30.86)
Change from Baseline to Cycle 9 Day 1	-0.7 (20.25)	0.0 (21.08)
Change from Baseline to Treatment Discontinuation	10.2 (32.27)	0.8 (21.19)

33. Secondary Outcome

Title	Maximum Change From Baseline in the EORTC QLQ-C30 Constipation Domain to Treatment Discontinuation Visit
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	160	74
Mean (Standard Deviation) [units on a scale]	-0.3 (27.60)	-3.5 (16.29)

34. Secondary Outcome

Title	Mean Change From Baseline in the EORTC QLQ-C30 Diarhoea
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	161	74
Baseline	15.7 (27.15)	12.6 (20.42)
Change from Baseline to Cycle 3 Day 1	-3.5 (25.71)	-3.1 (21.60)
Change from Baseline to Cycle 5 Day 1	-4.2 (29.78)	1.3 (22.07)
Change from Baseline to Cycle 7 Day 1	2.4 (32.62)	-4.2 (33.03)
Change from Baseline to Cycle 9 Day 1	-2.1 (22.42)	0.0 (36.51)
Change from Baseline to Treatment Discontinuation	1.6 (30.44)	0.0 (25.20)

35. Secondary Outcome

Title	Maximum Change From Baseline in the EORTC QLQ-C30 Diarhoea Domain to Treatment Discontinuation Visit
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	161	74
Least Squares Mean (Standard Deviation) [units on a scale]	-7.2 (25.25)	-5.8 (21.93)

36. Secondary Outcome

Title	Mean Change From Baseline in the EORTC QLQ-C30 Insomnia Domain
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	160	74
Baseline	29.4 (30.69)	25.7 (27.34)
Change from Baseline to Cycle 3 Day 1	-7.6 (27.06)	-4.7 (31.36)
Change from Baseline to Cycle 5 Day 1	-5.2 (24.97)	-6.4 (32.69)
Change from Baseline to Cycle 7 Day 1	-1.8 (29.83)	-16.7 (39.84)
Change from Baseline to Cycle 9 Day 1	-7.1 (30.25)	-16.7 (40.82)
Change from Baseline to Treatment Discontinuation	-3.2 (28.76)	0.8 (22.41)

37. Secondary Outcome

Title	Maximum Change From Baseline in the EORTC QLQ-C30 Insomnia Domain to Treatment Discontinuation Visit
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	160	74
Mean (Standard Deviation) [units on a scale]	-12.8 (28.64)	-7.6 (30.87)

38. Secondary Outcome

Title	Mean Change From Baseline in the EORTC QLQ-C30 Dyspnoea Domain to Treatment Discontinuation Visit
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	160	74
Baseline	26.5 (28.98)	21.2 (28.97)
Change from Baseline to Cycle 3 Day 1	-1.6 (27.76)	-0.8 (29.54)
Change from Baseline to Cycle 5 Day 1	-1.4 (26.88)	0.0 (33.99)
Change from Baseline to Cycle 7 Day 1	-2.9 (25.42)	4.2 (48.59)
Change from Baseline to Cycle 9 Day 1	1.4 (31.05)	5.6 (25.09)
Change from Baseline to Treatment Discontinuation	6.0 (28.22)	0.8 (23.56)

39. Secondary Outcome

Title	Maximum Change From Baseline in the EORTC QLQ-C30 Dyspnoea Domain to Treatment Discontinuation Visit
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	160	74
Mean (Standard Deviation) [units on a scale]	-7.3 (25.70)	-5.8 (27.55)

40. Secondary Outcome

Title	Mean Change From Baseline in the EORTC QLQ-C30 Appetite Loss Domain to Treatment Discontinuation Visit
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	160	74
Baseline	18.1 (27.69)	16.2 (26.02)
Change from Baseline to Cycle 3 Day 1	2.5 (31.25)	-0.8 (34.49)
Change from Baseline to Cycle 5 Day 1	1.9 (28.67)	5.1 (43.91)
Change from Baseline to Cycle 7 Day 1	-2.3 (23.45)	-12.5 (46.93)
Change from Baseline to Cycle 9 Day 1	-4.3 (27.47)	-11.1 (27.22)
Change from Baseline to Treatment Discontinuation	4.8 (32.42)	5.4 (27.15)

41. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	160	74
Mean (Standard Deviation) [units on a scale]	-4.8 (28.30)	-4.1 (29.59)

42. Secondary Outcome

Title	Mean Change From Baseline in the EORTC QLQ-C30 Financial Problems Domain to Treatment Discontinuation Visit
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	161	74
Baseline	19.5 (27.78)	10.8 (19.98)
Change from Baseline to Cycle 3 Day 1	-7.0 (25.61)	-0.8 (18.53)
Change from Baseline to Cycle 5 Day 1	-7.0 (27.55)	-3.8 (23.71)
Change from Baseline to Cycle 7 Day 1	-2.9 (33.50)	-4.2 (11.79)
Change from Baseline to Cycle 9 Day 1	-9.2 (31.62)	-5.6 (13.61)
Change from Baseline to Treatment Discontinuation	-4.3 (22.97)	1.6 (19.18)

43. Secondary Outcome

Title	Maximum Change From Baseline in the EORTC QLQ-C30 Financial Problems Domain to Treatment Discontinuation Visit
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	161	74
Mean (Standard Deviation) [units on a scale]	-10.9 (25.32)	-2.3 (19.78)

44. Secondary Outcome

Title	Mean Change From Baseline in the EORTC QLQ-C30 Global Health Status / QoL Domain
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	160	74
Baseline	59.0 (21.45)	58.4 (18.58)
Change from Baseline to Cycle 3 Day 1	-3.4 (21.89)	2.3 (18.66)
Change from Baseline to Cycle 5 Day 1	-0.7 (19.96)	3.2 (24.50)
Change from Baseline to Cycle 7 Day 1	1.0 (17.04)	7.3 (29.36)
Change from Baseline to Cycle 9 Day 1	4.3 (21.76)	8.3 (22.97)
Change from Baseline to Treatment Discontinuation	-5.8 (18.76)	-1.0 (19.26)

45. Secondary Outcome

Title	Maximum Change From Baseline in the EORTC QLQ-C30 Global Health Status / QoL Domain to Treatment Discontinuation Visit
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	160	74
Mean (Standard Deviation) [units on a scale]	4.6 (19.06)	5.6 (20.43)

46. Secondary Outcome

Title	Mean Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	161	74
Baseline	73.7 (21.52)	78.5 (18.56)
Change from Baseline to Cycle 3 Day 1	3.4 (19.64)	1.3 (20.77)
Change from Baseline to Cycle 5 Day 1	3.6 (17.01)	1.3 (16.11)
Change from Baseline to Cycle 7 Day 1	8.1 (20.53)	-3.1 (26.33)
Change from Baseline to Cycle 9 Day 1	4.5 (21.96)	1.4 (13.35)
Change from Baseline to Treatment Discontinuation	-1.3 (22.05)	-1.5 (16.50)

47. Secondary Outcome

Title	Maximum Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain to Treatment Discontinuation Visit
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Health Related Quality of Life (QoL) Evaluable Population includes participants who had evaluable QoL assessments.

Arm/Group Title	Lenalidomide	Investigators Choice
Arm/Group Description	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.	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.
Measure Participants	160	74
Mean (Standard Deviation) [units on a scale]	6.9 (21.79)	3.7 (17.11)

Adverse Events

Time Frame	From randomization of study drug to 30 days post-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.
Arm/Group Title	Lenalidomide		Investigator's Choice
Arm/Group Description	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.		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.
All Cause Mortality
	Lenalidomide		Investigator's Choice
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	119/167 (71.3%)		59/83 (71.1%)
Serious Adverse Events
	Lenalidomide		Investigator's Choice
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	75/167 (44.9%)		22/83 (26.5%)
Blood and lymphatic system disorders
ANAEMIA	6/167 (3.6%)		2/83 (2.4%)
AUTOIMMUNE HAEMOLYTIC ANAEMIA	0/167 (0%)		1/83 (1.2%)
FEBRILE NEUTROPENIA	6/167 (3.6%)		2/83 (2.4%)
LYMPH NODE PAIN	1/167 (0.6%)		1/83 (1.2%)
NEUTROPENIA	6/167 (3.6%)		0/83 (0%)
THROMBOCYTOPENIA	3/167 (1.8%)		2/83 (2.4%)
Cardiac disorders
ACUTE CORONARY SYNDROME	1/167 (0.6%)		0/83 (0%)
ACUTE MYOCARDIAL INFARCTION	1/167 (0.6%)		0/83 (0%)
ATRIAL FIBRILLATION	1/167 (0.6%)		1/83 (1.2%)
ATRIOVENTRICULAR BLOCK COMPLETE	1/167 (0.6%)		0/83 (0%)
ATRIOVENTRICULAR BLOCK SECOND DEGREE	1/167 (0.6%)		0/83 (0%)
CARDIAC ARREST	2/167 (1.2%)		0/83 (0%)
CARDIAC FAILURE	2/167 (1.2%)		1/83 (1.2%)
CARDIAC FAILURE ACUTE	0/167 (0%)		1/83 (1.2%)
CARDIAC FAILURE CONGESTIVE	1/167 (0.6%)		0/83 (0%)
CORONARY ARTERY DISEASE	1/167 (0.6%)		0/83 (0%)
LEFT VENTRICULAR FAILURE	1/167 (0.6%)		0/83 (0%)
MYOCARDIAL INFARCTION	1/167 (0.6%)		0/83 (0%)
SUPRAVENTRICULAR TACHYCARDIA	1/167 (0.6%)		0/83 (0%)
TACHYCARDIA	1/167 (0.6%)		0/83 (0%)
Ear and labyrinth disorders
DEAFNESS BILATERAL	1/167 (0.6%)		0/83 (0%)
VERTIGO	1/167 (0.6%)		0/83 (0%)
Eye disorders
RETINAL ARTERY OCCLUSION	1/167 (0.6%)		0/83 (0%)
Gastrointestinal disorders
ABDOMINAL PAIN	1/167 (0.6%)		0/83 (0%)
ABDOMINAL WALL HAEMATOMA	0/167 (0%)		1/83 (1.2%)
DIARRHOEA	6/167 (3.6%)		0/83 (0%)
GASTROINTESTINAL HAEMORRHAGE	1/167 (0.6%)		0/83 (0%)
LARGE INTESTINE PERFORATION	1/167 (0.6%)		0/83 (0%)
NAUSEA	1/167 (0.6%)		0/83 (0%)
OESOPHAGEAL ULCER HAEMORRHAGE	1/167 (0.6%)		0/83 (0%)
RECTAL HAEMORRHAGE	1/167 (0.6%)		1/83 (1.2%)
SMALL INTESTINAL OBSTRUCTION	0/167 (0%)		1/83 (1.2%)
VOMITING	2/167 (1.2%)		0/83 (0%)
General disorders
DEATH	1/167 (0.6%)		0/83 (0%)
FATIGUE	1/167 (0.6%)		0/83 (0%)
GENERAL PHYSICAL HEALTH DETERIORATION	3/167 (1.8%)		1/83 (1.2%)
MULTIPLE ORGAN DYSFUNCTION SYNDROME	2/167 (1.2%)		0/83 (0%)
OEDEMA PERIPHERAL	1/167 (0.6%)		0/83 (0%)
PYREXIA	5/167 (3%)		2/83 (2.4%)
SUDDEN DEATH	1/167 (0.6%)		0/83 (0%)
Hepatobiliary disorders
CHOLECYSTITIS	1/167 (0.6%)		0/83 (0%)
CHOLECYSTITIS ACUTE	1/167 (0.6%)		0/83 (0%)
HYPERBILIRUBINAEMIA	1/167 (0.6%)		0/83 (0%)
Immune system disorders
DRUG HYPERSENSITIVITY	0/167 (0%)		1/83 (1.2%)
Infections and infestations
ARTHRITIS INFECTIVE	1/167 (0.6%)		0/83 (0%)
ASPERGILLUS INFECTION	1/167 (0.6%)		0/83 (0%)
BRONCHITIS	2/167 (1.2%)		1/83 (1.2%)
BRONCHOPULMONARY ASPERGILLOSIS	0/167 (0%)		1/83 (1.2%)
CELLULITIS	1/167 (0.6%)		1/83 (1.2%)
LOWER RESPIRATORY TRACT INFECTION	3/167 (1.8%)		1/83 (1.2%)
LUNG INFECTION	2/167 (1.2%)		0/83 (0%)
MENINGITIS VIRAL	1/167 (0.6%)		0/83 (0%)
NEUTROPENIC SEPSIS	1/167 (0.6%)		0/83 (0%)
PNEUMONIA	6/167 (3.6%)		3/83 (3.6%)
PNEUMONIA MORAXELLA	0/167 (0%)		1/83 (1.2%)
PNEUMONIA STREPTOCOCCAL	1/167 (0.6%)		0/83 (0%)
PSEUDOMEMBRANOUS COLITIS	1/167 (0.6%)		0/83 (0%)
SEPTIC SHOCK	1/167 (0.6%)		0/83 (0%)
SINUSITIS	1/167 (0.6%)		0/83 (0%)
SKIN INFECTION	1/167 (0.6%)		0/83 (0%)
STAPHYLOCOCCAL BACTERAEMIA	1/167 (0.6%)		0/83 (0%)
STAPHYLOCOCCAL SEPSIS	1/167 (0.6%)		0/83 (0%)
UPPER RESPIRATORY TRACT INFECTION	1/167 (0.6%)		0/83 (0%)
URINARY TRACT INFECTION	2/167 (1.2%)		0/83 (0%)
UROSEPSIS	1/167 (0.6%)		0/83 (0%)
Injury, poisoning and procedural complications
FACIAL BONES FRACTURE	1/167 (0.6%)		0/83 (0%)
TOXICITY TO VARIOUS AGENTS	0/167 (0%)		1/83 (1.2%)
Investigations
WEIGHT DECREASED	1/167 (0.6%)		0/83 (0%)
Metabolism and nutrition disorders
CACHEXIA	1/167 (0.6%)		0/83 (0%)
DEHYDRATION	1/167 (0.6%)		0/83 (0%)
DIABETES MELLITUS	0/167 (0%)		1/83 (1.2%)
HYPERKALAEMIA	1/167 (0.6%)		0/83 (0%)
HYPOALBUMINAEMIA	1/167 (0.6%)		0/83 (0%)
HYPOPROTEINAEMIA	1/167 (0.6%)		0/83 (0%)
Musculoskeletal and connective tissue disorders
ARTHRITIS	1/167 (0.6%)		0/83 (0%)
OSTEONECROSIS	1/167 (0.6%)		1/83 (1.2%)
PAIN IN EXTREMITY	1/167 (0.6%)		0/83 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ACUTE LYMPHOCYTIC LEUKAEMIA	3/167 (1.8%)		0/83 (0%)
BASAL CELL CARCINOMA	2/167 (1.2%)		0/83 (0%)
CANCER PAIN	1/167 (0.6%)		0/83 (0%)
DIFFUSE LARGE B-CELL LYMPHOMA	0/167 (0%)		1/83 (1.2%)
LIPOSARCOMA	1/167 (0.6%)		0/83 (0%)
MANTLE CELL LYMPHOMA	1/167 (0.6%)		3/83 (3.6%)
MENINGIOMA BENIGN	0/167 (0%)		1/83 (1.2%)
METASTASES TO LUNG	1/167 (0.6%)		0/83 (0%)
METASTATIC SQUAMOUS CELL CARCINOMA	1/167 (0.6%)		0/83 (0%)
SQUAMOUS CELL CARCINOMA OF SKIN	2/167 (1.2%)		0/83 (0%)
TUMOUR FLARE	1/167 (0.6%)		0/83 (0%)
Nervous system disorders
CEREBRAL HAEMORRHAGE	1/167 (0.6%)		0/83 (0%)
CEREBROVASCULAR ACCIDENT	1/167 (0.6%)		0/83 (0%)
HEMIANOPIA HETERONYMOUS	1/167 (0.6%)		0/83 (0%)
ISCHAEMIC STROKE	1/167 (0.6%)		0/83 (0%)
SEIZURE	1/167 (0.6%)		0/83 (0%)
TRANSIENT ISCHAEMIC ATTACK	1/167 (0.6%)		0/83 (0%)
Renal and urinary disorders
ANURIA	0/167 (0%)		1/83 (1.2%)
CHRONIC KIDNEY DISEASE	1/167 (0.6%)		0/83 (0%)
CYSTITIS HAEMORRHAGIC	1/167 (0.6%)		0/83 (0%)
OLIGURIA	0/167 (0%)		1/83 (1.2%)
RENAL FAILURE	1/167 (0.6%)		0/83 (0%)
Reproductive system and breast disorders
OEDEMA GENITAL	1/167 (0.6%)		0/83 (0%)
UTERINE POLYP	1/167 (0.6%)		0/83 (0%)
Respiratory, thoracic and mediastinal disorders
ASPIRATION	1/167 (0.6%)		0/83 (0%)
BRONCHITIS CHRONIC	1/167 (0.6%)		0/83 (0%)
COUGH	0/167 (0%)		1/83 (1.2%)
DYSPNOEA	3/167 (1.8%)		1/83 (1.2%)
INTERSTITIAL LUNG DISEASE	1/167 (0.6%)		0/83 (0%)
PHARYNGEAL INFLAMMATION	1/167 (0.6%)		0/83 (0%)
PLEURAL EFFUSION	2/167 (1.2%)		0/83 (0%)
PLEURISY	1/167 (0.6%)		0/83 (0%)
PULMONARY EMBOLISM	6/167 (3.6%)		0/83 (0%)
RESPIRATORY DISTRESS	1/167 (0.6%)		0/83 (0%)
RESPIRATORY FAILURE	1/167 (0.6%)		0/83 (0%)
VOCAL CORD DISORDER	1/167 (0.6%)		0/83 (0%)
Skin and subcutaneous tissue disorders
DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS	1/167 (0.6%)		0/83 (0%)
Vascular disorders
HAEMORRHAGE	1/167 (0.6%)		0/83 (0%)
HYPERTENSION	1/167 (0.6%)		0/83 (0%)
HYPOTENSION	2/167 (1.2%)		0/83 (0%)
VENOUS THROMBOSIS LIMB	1/167 (0.6%)		0/83 (0%)
Other (Not Including Serious) Adverse Events
	Lenalidomide		Investigator's Choice
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	146/167 (87.4%)		61/83 (73.5%)
Blood and lymphatic system disorders
ANAEMIA	45/167 (26.9%)		18/83 (21.7%)
LEUKOPENIA	29/167 (17.4%)		18/83 (21.7%)
LYMPHOPENIA	8/167 (4.8%)		6/83 (7.2%)
NEUTROPENIA	86/167 (51.5%)		29/83 (34.9%)
THROMBOCYTOPENIA	63/167 (37.7%)		33/83 (39.8%)
Ear and labyrinth disorders
VERTIGO	9/167 (5.4%)		0/83 (0%)
Gastrointestinal disorders
ABDOMINAL PAIN	16/167 (9.6%)		4/83 (4.8%)
ABDOMINAL PAIN UPPER	7/167 (4.2%)		6/83 (7.2%)
CONSTIPATION	29/167 (17.4%)		5/83 (6%)
DIARRHOEA	36/167 (21.6%)		8/83 (9.6%)
DYSPEPSIA	9/167 (5.4%)		3/83 (3.6%)
NAUSEA	17/167 (10.2%)		13/83 (15.7%)
VOMITING	8/167 (4.8%)		9/83 (10.8%)
General disorders
ASTHENIA	26/167 (15.6%)		11/83 (13.3%)
FATIGUE	34/167 (20.4%)		4/83 (4.8%)
OEDEMA PERIPHERAL	16/167 (9.6%)		9/83 (10.8%)
PYREXIA	26/167 (15.6%)		9/83 (10.8%)
Infections and infestations
BRONCHITIS	15/167 (9%)		8/83 (9.6%)
CONJUNCTIVITIS	9/167 (5.4%)		0/83 (0%)
INFLUENZA	9/167 (5.4%)		1/83 (1.2%)
NASOPHARYNGITIS	25/167 (15%)		5/83 (6%)
RESPIRATORY TRACT INFECTION	10/167 (6%)		0/83 (0%)
UPPER RESPIRATORY TRACT INFECTION	23/167 (13.8%)		5/83 (6%)
Investigations
ALANINE AMINOTRANSFERASE INCREASED	8/167 (4.8%)		5/83 (6%)
Metabolism and nutrition disorders
DECREASED APPETITE	22/167 (13.2%)		3/83 (3.6%)
HYPOALBUMINAEMIA	9/167 (5.4%)		1/83 (1.2%)
HYPOKALAEMIA	15/167 (9%)		1/83 (1.2%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	12/167 (7.2%)		2/83 (2.4%)
BACK PAIN	16/167 (9.6%)		0/83 (0%)
MUSCLE SPASMS	13/167 (7.8%)		3/83 (3.6%)
PAIN IN EXTREMITY	13/167 (7.8%)		0/83 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
TUMOUR FLARE	15/167 (9%)		0/83 (0%)
Nervous system disorders
HEADACHE	14/167 (8.4%)		0/83 (0%)
PARAESTHESIA	10/167 (6%)		1/83 (1.2%)
Psychiatric disorders
INSOMNIA	9/167 (5.4%)		1/83 (1.2%)
Respiratory, thoracic and mediastinal disorders
COUGH	20/167 (12%)		4/83 (4.8%)
DYSPNOEA	10/167 (6%)		6/83 (7.2%)
Skin and subcutaneous tissue disorders
DERMATITIS ALLERGIC	9/167 (5.4%)		2/83 (2.4%)
PRURITUS	15/167 (9%)		3/83 (3.6%)
RASH	19/167 (11.4%)		3/83 (3.6%)
Vascular disorders
HYPERTENSION	15/167 (9%)		7/83 (8.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Results from a center cannot be submitted for publication before results of multicenter study are published unless it is > 1 year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to 90 additional days. Investigator must delete confidential information before submission and defer publication to permit patent applications.