A Study to Compare MPR With MP in Newly Diagnosed Multiple Myeloma Subjects 65 Years Old or Older.

• Sponsor: Celgene Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00405756
• Collaborator: (none)
• Enrollment: 459
• Locations: 98
• Arms: 3
• Duration (Months): 111
• Patients Per Site: 4.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether lenalidomide is safe and effective in the treatment of patients with newly diagnosed Multiple Myeloma who are 65 years of age or older.

Condition or Disease	Intervention/Treatment	Phase
Newly Diagnosed Multiple Myeloma	Drug: Lenalidomide: Double-blind Induction; Drug: Melphalan; Drug: Prednisone; Drug: Aspirin; Drug: Placebo; Drug: Lenalidomide: Double-blind Maintenance; Drug: Lenalidomide: Open-label	Phase 3

Detailed Description

The three phases for the study as originally defined and as represented in the results of 11

May 2010 are:

Double-blind Treatment Phase: Induction Melphalan/prednisone and lenalidomide 10 mg (MPR) (2 treatment arms), or melphalan/prednisone and placebo (MPp) (1 treatment arm) for up to 9 cycles. If disease progression, subjects have the option to enter into the Open-Label Extension Phase. There is also an option to enter into the Follow-Up Phase. If the disease has not progressed, subject can continue on blinded therapy into Maintenance.

Double-blind Treatment Phase: Maintenance One MPR treatment arm (MPR+R) will continue taking lenalidomide 10 mg in Maintenance. The other MPR treatment arm (MPR+p) will take placebo in Maintenance. The MP p treatment arm will take placebo in Maintenance (MPp+p). If disease progression, subjects have the option to enter the Open-Label Extension Phase to obtain treatment with lenalidomide, or to enter into the Follow-up Phase.

Open-label Extension Phase:

Treatment consists of oral lenalidomide (up to 25 mg) with or without dexamethasone until disease progression or treatment is discontinued for any reason until all study subjects are followed for at least 5 years from the date of randomization or have died. Subjects who discontinue from the Open-Label Extension Phase prior to completing a total of 5 years in the study will enter the Follow-up Phase.

Follow-up Phase:

Subjects are followed for overall survival and subsequent anti-myeloma treatment regimens until all subjects in this study are followed for at least 5 years from randomization or have died.

The pre-planned interim analysis for the Independent Data Monitoring Committee (IDMC) showed that the difference in progression-free survival (PFS) between treatment arms MPR+R and MPp+p (the defined primary comparative analysis for this study) surpassed the pre-specified O'Brien-Fleming boundary for superiority. The IDMC recommended the release of this information to the sponsor and also recommended that all patient and physician study participants receive information concerning the full findings of the MM-015 interim analysis. Therefore, due to these recommendations from the IDMC, treatment-arm codes were sent to the clinical trial centers to unblind the treatment arms of their study subjects once the amended protocol was reviewed and approved by the respective country Health Authorities and Ethics Committees. Subject participation in the MM-015 study continued after unblinding to obtain long-term data for all study endpoints, including overall survival.

When the study was unblinded, subjects still on protocol therapy had completed the Double-Blind Induction, and were on monotherapy in Double-Blind Maintenance. Subjects in arm MPR+R continued their monotherapy on lenalidomide. Subjects in arms MPR+p and MPp+p discontinued their placebo monotherapy and went into an observation period in which no antimyeloma therapy was taken. If disease progressed for any subject, the investigator had the option of entering the subject in Open Label Extension Phase to receive lenalidomide therapy (up to 25 mg daily) or the Follow-up Phase. All subjects were to be followed for at least 5 years from the start of the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 459 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III, Multicentre, Randomized, Double-Blind, Placebo-Controlled, 3-Arm Parallel Group Study To Determine The Efficacy And Safety Of Lenalidomde (Revlimid®) In Combination With Melphalan And Prednisone Versus Placebo Plus Melphalan And Prednisone In Subjects With Newly Diagnosed Multiple Myeloma Who Are 65 Years Of Age Or Older
• Study Start Date: Jan 1, 2007
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Apr 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MPR+R Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Drug: Lenalidomide: Double-blind Induction; Double-blind Induction: the starting lenalidomide oral dosing regimen was 10 mg once daily on Days 1 through 21 of each 28 day cycle for up to 9 cycles. Dose was reduced if needed due to dose-limiting toxicity.; Other Names: Revlimid ; Drug: Melphalan; Double-blind Induction: the starting melphalan oral dosing regimen in all 3 treatment arms was 0.18 mg/kg daily on Days 1 through 4 of each 28-day cycle for up to 9 cycles. Dose was reduced if needed due to dose-limiting toxicity.; Other Names: Alkeran ; Drug: Prednisone; Double-blind induction: the starting prednisone oral dosing regimen in all 3 treatment arms was 2 mg/kg daily on Days 1 through 4 of each 28-day cycle for up to 9 cycles. Dose was reduced if needed due to dose-limiting toxicity.; Drug: Aspirin; Double-blind induction: low-dose aspirin 75 mg to 100 mg daily for all treatment arms. Double-blind maintenance: at the investigator's discretion; Drug: Lenalidomide: Double-blind Maintenance; Single-agent oral lenalidomide 10 mg once daily on Days 1 through 21 of each 28-day cycle from cycle 10 to disease progression.; Other Names: Revlimid ; Drug: Lenalidomide: Open-label; Any study participant who had progressive disease had the option of open-label lenalidomide up to 25 mg daily on Days 1 through 21 of each 28-day cycle.; Other Names: Revlimid
Experimental: MPR+p Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Drug: Lenalidomide: Double-blind Induction; Double-blind Induction: the starting lenalidomide oral dosing regimen was 10 mg once daily on Days 1 through 21 of each 28 day cycle for up to 9 cycles. Dose was reduced if needed due to dose-limiting toxicity.; Other Names: Revlimid ; Drug: Melphalan; Double-blind Induction: the starting melphalan oral dosing regimen in all 3 treatment arms was 0.18 mg/kg daily on Days 1 through 4 of each 28-day cycle for up to 9 cycles. Dose was reduced if needed due to dose-limiting toxicity.; Other Names: Alkeran ; Drug: Prednisone; Double-blind induction: the starting prednisone oral dosing regimen in all 3 treatment arms was 2 mg/kg daily on Days 1 through 4 of each 28-day cycle for up to 9 cycles. Dose was reduced if needed due to dose-limiting toxicity.; Drug: Aspirin; Double-blind induction: low-dose aspirin 75 mg to 100 mg daily for all treatment arms. Double-blind maintenance: at the investigator's discretion; Drug: Placebo; Double-blind induction: participants in treatment arm MPp+p received placebo once daily on Days 1 through 21 of each 28-day cycle for up to 9 cycles. Double-blind maintenance: participants in treatment arms MPR+p and MPp+p received placebo once daily on Days 1 through 21 of each 28-day cycle from cycle 10 to disease progression.; Drug: Lenalidomide: Open-label; Any study participant who had progressive disease had the option of open-label lenalidomide up to 25 mg daily on Days 1 through 21 of each 28-day cycle.; Other Names: Revlimid
Other: MPp+p Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Drug: Melphalan; Double-blind Induction: the starting melphalan oral dosing regimen in all 3 treatment arms was 0.18 mg/kg daily on Days 1 through 4 of each 28-day cycle for up to 9 cycles. Dose was reduced if needed due to dose-limiting toxicity.; Other Names: Alkeran ; Drug: Prednisone; Double-blind induction: the starting prednisone oral dosing regimen in all 3 treatment arms was 2 mg/kg daily on Days 1 through 4 of each 28-day cycle for up to 9 cycles. Dose was reduced if needed due to dose-limiting toxicity.; Drug: Aspirin; Double-blind induction: low-dose aspirin 75 mg to 100 mg daily for all treatment arms. Double-blind maintenance: at the investigator's discretion; Drug: Placebo; Double-blind induction: participants in treatment arm MPp+p received placebo once daily on Days 1 through 21 of each 28-day cycle for up to 9 cycles. Double-blind maintenance: participants in treatment arms MPR+p and MPp+p received placebo once daily on Days 1 through 21 of each 28-day cycle from cycle 10 to disease progression.; Drug: Lenalidomide: Open-label; Any study participant who had progressive disease had the option of open-label lenalidomide up to 25 mg daily on Days 1 through 21 of each 28-day cycle.; Other Names: Revlimid

Outcome Measures

Primary Outcome Measures

1. Kaplan Meier Estimates of Progression-free Survival (PFS) Based on the Response Assessment by the Central Adjudication Committee (CAC) [up to 165 weeks]

   Data as of 11 May 2010 cutoff. PFS was calculated as the time from randomization to the earlier of the first documentation of progressive disease (PD) as determined by the CAC, or death on study due to any cause. PD was based on the European Group for Blood and Marrow Transplantation/International Bone Marrow Transplant Registry/Autologous Bone Marrow Transplant Registry [EBMT/IBMTR/ABMTR] criteria. PD criteria includes increasing monoclonal paraprotein levels, bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.

Secondary Outcome Measures

1. Kaplan Meier Estimates of Progression-free Survival (PFS) From Start of Maintenance Therapy Period Based on the Response Assessment by the Central Adjudication Committee (CAC) [Approximately week 37 (start of cycle 10) to week 165]

   Data as of 11 May 2010 cutoff. PFS calculated from the start of the Maintenance period to the earlier of the first documentation of progressive disease (PD) as determined by the CAC, or death on study due to any cause. PD was based on the European Group for Blood and Marrow Transplantation/International Bone Marrow Transplant Registry/Autologous Bone Marrow Transplant Registry [EBMT/IBMTR/ABMTR] criteria. PD criteria includes increasing monoclonal paraprotein levels, bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.

2. Kaplan Meier Estimates of Overall Survival (OS) [up to 177 weeks]

   Data as of 11 May 2010 cutoff. Overall survival (OS) was defined as the time between randomization and death. Participants who died, regardless of the cause of death, were considered to have had an event. Participants who were lost to follow-up prior to the end of the trial, or who were withdrawn from the trial, were censored at the time of last contact. Participants who were still being treated were censored at the last available date available, or clinical cut-off date, if it was earlier.

3. Kaplan Meier Estimates of Time to Progression (TTP) Based on the Response Assessment by the Central Adjudication Committee (CAC) [up to 165 weeks]

   Data as of 11 May 2010 cutoff. TTP was the time between randomization and disease progression as determined by the CAC. PD was based on the European Group for Blood and Marrow Transplantation/International Bone Marrow Transplant Registry/Autologous Bone Marrow Transplant Registry [EBMT/IBMTR/ABMTR] criteria. PD criteria includes increasing monoclonal paraprotein levels, bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.

4. Number of Participants in Disease Response Categories Representing Their Best Response During the Double-blind Treatment Period [Up to 165 weeks]

   Data as of 11 May 2010 cutoff. Best response was determined by the Central Assessment Committee (CAC) based on the European Group for Blood and Marrow Transplantation (EBMT) criteria: Complete Response (CR)-absence of serum and urine monoclonal paraprotein for 6 weeks, plus no increase in size or number of bone lesions, plus other factors); Partial Response (PR)-not all CR criteria, plus >=50% reduction in serum monoclonal paraprotein plus others; Stable Disease (SD)- not PR or PD; Progressive Disease (PD)- reappearance of monoclonal paraprotein, bone lesions, other; Not Evaluable (NE).

5. Time to First Response [Up to 66 weeks]

   Data as of 11 May 2010 cutoff. Time to first response was defined as the time from start of treatment until first response as assessed by the Central Assessment Committee (CMC) based on European Group for Blood and Marrow Transplantation (EBMT) criteria.

6. Kaplan Meier Estimates for Duration of Response as Determined by the Central Adjudication Committee (CAC) [Up to 149 weeks]

   Data as of 11 May 2010 cutoff. Duration of myeloma response was defined as the time from the initial response date to the earlier of progressive disease (PD) as determined by the CAC or death on study. PD was based on the European Group for Blood and Marrow Transplantation/International Bone Marrow Transplant Registry/Autologous Bone Marrow Transplant Registry [EBMT/IBMTR/ABMTR] criteria. PD criteria includes increasing monoclonal paraprotein levels, bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.

7. Kaplan Meier Estimates for Time to Next Antimyeloma Therapy [Up to 168 weeks]

   Data as of 11 May 2010 cutoff. Time to the next antimyeloma therapy was defined as time from randomization to the start of another non-protocol antimyeloma therapy. Participants who do not receive another anti-myeloma therapy were censored at the last assessment or follow-up visit known to have received no new therapy.

8. Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period [Up to 169 weeks (Double-blind therapy period plus 4 weeks)]

   Data as of 11 May 2010 cutoff. Participant counts in different categories of TEAEs during the double-blind treatment period. A TEAE is as any AE occurring or worsening on or after the first treatment of any study drug, and within 30 days after the last dose of the last study drug. Severity grades according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE) on a 1-5 scale: Grade 1= Mild AE, Grade 2= Moderate AE, Grade 3= Severe AE, Grade 4= Life-threatening or disabling AE, Grade 5=Death related to AE. Dose reduction includes reduction with or without interruption.

9. Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Quality of Life Scale [Baseline (Day 0), Months 4, 7, 10, 13, 16]

   Data as of 11 May 2010 cutoff. EORTC QLC-C30 is a 30-item questionnaire to assess the quality of life in cancer patients. EORTC QLQ-C30 includes functional scales (physical, role, cognitive, emotional, social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and other (dyspnoea, appetite loss, insomnia, constipation/diarrhea, financial difficulties). Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); two used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better quality of life.

10. Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Physical Functioning Scale [Baseline (Day 0), Months 4, 7, 10, 13, 16]

    Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score=better level of physical functioning.

11. Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Role Functioning Scale [Baseline (Day 0), Months 4, 7, 10, 13, 16]

    Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score=better level of role functioning.

12. Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Emotional Functioning Scale [Baseline (Day 0), Months 4, 7, 10, 13, 16]

    Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better level of emotional functioning.

13. Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Congitive Functioning Scale [Baseline (Day 0), Months 4, 7, 10, 13, 16]

    Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better level of cognitive functioning.

14. Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Social Functioning Scale [Baseline (Day 0), Months 4, 7, 10, 13, 16]

    Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better level of social functioning.

15. Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Scale [Baseline (Day 0), Months 4, 7, 10, 13, 16]

    Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the fatigue scale = higher level of symptomatology/problems.

16. Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Nausea and Vomiting Scale [Baseline (Day 0), Months 4, 7, 10, 13, 16]

    Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the nausea/vomiting scale = higher level of symptomatology/problems.

17. Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Pain Scale [Baseline (Day 0), Months 4, 7, 10, 13, 16]

    Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the pain scale = higher level of symptomatology/problems.

18. Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Dyspnoea Scale [Baseline (Day 0), Months 4, 7, 10, 13, 16]

    Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the dyspnoea scale = higher level of symptomatology/problems.

19. Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Insomnia Scale [Baseline (Day 0), Months 4, 7, 10, 13, 16]

    Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the insomnia scale = higher level of symptomatology/problems.

20. Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Appetite Loss Scale [Baseline (Day 0), Months 4, 7, 10, 13, 16]

    Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the appetite loss scale = higher level of symptomatology/problems.

21. Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Constipation Scale [Baseline (Day 0), Months 4, 7, 10, 13, 16]

    Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the constipation scale = higher level of symptomatology/problems.

22. Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Diarrhoea Scale [Baseline (Day 0), Months 4, 7, 10, 13, 16]

    Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the diarrhea scale = higher level of symptomatology/problems.

23. Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Financial Difficulties Scale [Baseline (Day 0), Months 4, 7, 10, 13, 16]

    Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a problem scale like the financial problems scale = higher level of financial problems.

24. Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms Scale [Baseline (Day 0), Months 4, 7, 10, 13, 16]

    Data as of 11 May 2010 cutoff. EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. EORTC QLQ-MY20 includes four scales: disease symptoms, treatment side-effects, future perspective, and body image. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale; higher score for the disease symptoms scale = higher level of symptomatology.

25. Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Side Effects of Treatment Scale [Baseline (Day 0), Months 4, 7, 10, 13, 16]

    Data as of 11 May 2010 cutoff. EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale; higher score for the side effects scale = higher level of symptomatology.

26. Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Future Perspective Scale [Baseline (Day 0), Months 4, 7, 10, 13, 16]

    Data as of 11 May 2010 cutoff. EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale. For the future perspective scale, higher score = better perspective of the future.

27. Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Body Image Scale [Baseline (Day 0), Months 4, 7, 10, 13, 16]

    Data as of 11 May 2010 cutoff. EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale. For the body image scale, higher scores = better body image.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

1. Must understand and voluntarily sign an informed consent form

2. Age greater than or equal to 65 years at the time of signing the informed consent

3. Newly diagnosed with symptomatic multiple myeloma as defined by the 3 criteria below:

MM diagnostic criteria (all of next 3 required)

1. Monoclonal plasma cells in the bone marrow greater than or equal to 10% and/or presence of a biopsy-proven plasmacytoma

2. Monoclonal protein present in the serum and/or urine

3. Myeloma-related organ dysfunction (at least one of the following) [C] Calcium elevation in the blood (serum calcium >10.5mg/dl or upper limit of normal) [R] Renal insufficiency (serum creatinine >2mg/dl) [A] Anemia (hemoglobin <10g/dl or 2g < normal) [B] Lytic bone lesions or osteoporosis AND have measurable disease as defined by the following; IgG multiple myeloma: Serum monoclonal paraprotein (M-protein) level greater than or equal to 1.0 g/dL or urine M-protein level greater than or equal to 200 mg/24 hours IgA multiple myeloma: Serum M-protein level greater than or equal to 0.5 g/dL or urine M-protein level greater than or equal to 200 mg/24 hours IgD multiple myeloma: Serum M-protein level greater than or equal to 0.05 g/dL or urine

M-protein level greater than or equal to 200 mg/24 hours Light chain multiple myeloma:

Serum M-protein level greater than or equal to 1.0 g/dL or urine M-protein level greater than or equal to 200 mg/24 hours IgM multiple myeloma (IgM M-protein plus lytic bone disease documented by skeletal survey plain films): Serum M-protein level greater than or equal to 1.0g/dL or urine M-protein level greater than or equal to 200mg/24hours

1. Karnofsky performance status greater than or equal to 60%.

2. Able to adhere to the study visit schedule and other protocol requirements.

3. Women of Childbearing potential (WCBP) must:

1. Have a negative medically supervised pregnancy test prior to the start of study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study therapy. This applies even if the subject practices and continues sexual abstinence.

b Either commit to continued abstinence from heterosexual intercourse (which must be reviewed on a monthly basis) or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting study drug, during the study therapy (including dose interruptions), and for 28 days after discontinuation of study therapy.

1. Males Subjects must:

2. Agree to use a condom during sexual contact with a WCBP, even if they have had a vasectomy, throughout study drug therapy, during any dose interruption and after the cessation of study therapy.

3. Agree to not donate semen during study drug therapy and for a period after end of study drug therapy.

4. All subjects must

5. Have an understanding that the study drug could have potential teratogenic risk.

6. Agree to abstain from donating blood while taking study drug therapy and following discontinuation of study drug therapy.

7. Agree not to share study medication with another person.

8. All patients must be counseled about pregnancy precautions and risks of fetal exposure.

Female Subjects:

Females of childbearing potential (FCBP) with regular cycles must agree to have pregnancy tests weekly for the first 28 days of study participation and then every 28 days while on study, at study discontinuation, and at day 28 following discontinuation from the study. If menstrual cycles are irregular, the pregnancy testing must occur weekly for the first 28 days and then every 14 days while on study, at study discontinuation, and at days 14 and 28 following discontinuation from the study.

In addition to the required pregnancy testing, the Investigator must confirm with FCBP that she is continuing to use two reliable methods of birth control at each visit. Counseling about pregnancy precautions and the potential risks of fetal exposure must be conducted at a minimum of every 28 days. During counseling, subjects must be reminded to not share study drug and to not donate blood.

Pregnancy testing and counseling must be performed if a subject misses her period or if her pregnancy test or her menstrual bleeding is abnormal. Study drug treatment must be discontinued during this evaluation.

Females must agree to abstain from breastfeeding during study participation and for at least 28 days after the discontinuation from the study.

Male Subjects:

Counseling about the requirement for latex condom use during sexual contact with females of childbearing potential and the potential risks of fetal exposure must be conducted at a minimum of every 28 days. During counseling, subjects must be reminded to not share study drug and to not donate blood, sperm, or semen.

If pregnancy or a positive pregnancy test does occur in a study subject or the partner of a study subject during study participation, study drug must be immediately discontinued.

Exclusion Criteria

1. Previous treatment with antimyeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid [i.e., less than or equal to the equivalent of dexamethasone 40 mg/day for 4 days; such a short course of steroid treatment must not have been given within 28 days [4 weeks] of randomization]).

2. Any serious medical condition, including the presence of laboratory abnormalities, which places the subject at an unacceptable risk if he or she participates in this study or confounds experimental the ability to interpret data from the study.

3. Pregnant or lactating females.

4. Radiotherapy within 14 days (2 weeks) of randomization.

5. Plasmapheresis within 28 days (4 weeks) of randomization.

6. Any of the following laboratory abnormalities:

Absolute neutrophil count (ANC) < 1,500 cells/mL (1.510^9/L) Platelet count < 75,000 cells/uL (7510^9/L) for subjects in whom < 50% of bone marrow nucleated cells are plasma cells; but platelet count <30,000/uL for subjects in whom >= 50% of bone marrow nucleated cells are plasma cells Haemoglobin < 8.0 g/dL (80 g/L) Serum creatinine > 2.5 mg/dL (221 µmol/L) Serum aspartate aminotransferase (SGOT/AST) or alanine aminotransferase (SGPT/ALT) > 3.0 times upper limit of normal (ULN)

1. Prior history of malignancies, other than multiple myeloma, unless the subject has been free of the disease for greater than or equal to 3 years.

Exceptions include the following:

Basal cell carcinoma of the skin Squamous cell carcinoma of the skin Carcinoma in situ of the cervix Carcinoma in situ of the breast Incidental histologic finding of prostate cancer (TNM Classification of Malignant Tumours (TNM) stage of T1a or T1b)

1. Neuropathy of >= grade 2 severity.

2. Known human immunodeficiency virus (HIV) positivity or active infectious hepatitis, type A, B or C.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hematology Oncology Clinics of Australia, Level 5, Mater Medical Centre	South Brisbane	Queensland	Australia	4101
2	Royal Adelaide Hospital Institute of Medical and Veterinary Science	Adelaide	South Australia	Australia	5000
3	Royal Prince Alfred Hospital	Camperdown		Australia	2050
4	Peter MacCallum Cancer Centre Divsion of Haematology Medical Oncology	East Melbourne		Australia	3006
5	Frankston Hospital	Frankston		Australia	3199
6	The Alfred Hospital	Melbourne		Australia	3141
7	Sir Charles Gairdner Hospital	Nedlands		Australia	6009
8	Princess Alexandra Hospital	Woolloongabba		Australia	4102
9	University Hospital Innsbruck	Innsbruck		Austria	6020
10	University Hospital of Salzburg St Johanns Spital	Salzburg		Austria	5020
11	Medical University of Vienna	Vienna		Austria	1090
12	Wilhelminenspital	Vienna		Austria	1160
13	Medical University of Vienna	Vienna		Austria	A-1090
14	Republican Scientific and Practical Centre of Radiation Medicine and Human Ecology	Gomel		Belarus	246 042
15	City Clinical Hospital 9	Minsk		Belarus	220116
16	AZ St-Jan Brugge Oostende AV	Brugge		Belgium	8000
17	AZ-VUB	Brussels		Belgium	1090
18	UZ Gasthuisberg	Leuven		Belgium	3000
19	Centre Hospitalier Universitaire de Liege	Liege		Belgium	4000
20	Fakultni nemocnice Brno	Brno		Czech Republic	625 00
21	Fakultni nemocnice Hradec Kralove	Hradec Kralove		Czech Republic	500 05
22	Fakultni Nemocnice Olomouc	Olomouc		Czech Republic	77520
23	Vseobecna Fakultni Nemocnice v Praze	Prague		Czech Republic	128 081
24	Hæmatologisk afd. B Aalborg Sygehus Syd	Aalborg		Denmark	9000
25	Medicinsk afd. Vejle Sygehus	Vejle		Denmark	7100
26	CHU	Caen		France	14033
27	CH - Hôpital Dupuytren	Limoges Cedex 1		France	87042
28	CHU Montpellier- Hopital Lapeyronie	Montpellier Cedex 5		France	34295
29	Assistance Publique - Hôpitaux de Paris AP-HP	Paris		France	75475
30	CHU Purpan	Toulouse cedex 9		France	TSA 40031-31059
31	Ltd M.Zodelava Hematology Centre	Tbilisi		Georgia	0112
32	Institute of Hematology and Transfusiology	Tbilisi		Georgia	0177
33	Medizinische Klinik und Poliklinik II der Charite Campus Mitte	Berlin		Germany	10117
34	Universitatsklinikum Carl Gustav Carus an der TU Dresden	Dresden		Germany	D-01307
35	Universitatsklinikum Freiburg Medizinische Klinik und Poliklinik	Freiburg		Germany	D-79106
36	Ernst-Moritz-Arndt-Universität Greifswald	Greifswald		Germany	17487
37	Universitaetsklinikum Heidelberg Medizinische Klinik und Poliklinik V	Heidelberg		Germany	69120
38	Medizinische Klinik und Poliklinik II	Leipzig		Germany	D-04103
39	Poliklinik A	Münster		Germany	47589
40	Medizinische Klinik - Abteilung II	Tübingen		Germany	72076
41	Medizinische Universitatsklinik	Ulm		Germany	89081
42	Medizinische Klinik und Poliklinik II des Universitatsklinikums Wurzburg	Würzburg		Germany	97080
43	G. GENNIMATAS General Hospital of Athens Department of Hematolgosy	Athens		Greece	115 27
44	General Air Force Hospital	Athens		Greece	11525
45	Alexandra General Hospital of Athens	Athens		Greece	11528
46	Hope Directorate Haematology Oncology Service St. James Hospital	Dublin		Ireland	8
47	Midlands Regional	Tullamore / Co Offally		Ireland
48	Rambam Medical Center	Haifa		Israel	31096
49	Hadassah University Hospital	Jerusalem		Israel	91120
50	Hematology Institute, Hemato-Oncology Division,Davidoff Cancer Center, Rabin MC Beilinson Hospital	Petch Tikva		Israel	49100
51	The Chaim Sheba Medical Center	Tel Hashomer		Israel	52621
52	Policlinico S. Orsola	Bologna		Italy	40138
53	A.O.U. San Martino	Genova		Italy	16132
54	Dipartmento Oncologico Struttura Complessa di ematlologiaA.O. Ospedale Niguarda Ca Granda	Milano		Italy	20162
55	Policlinico San Matteo Universita Di Pavia	Pavia 2		Italy	27100
56	Divisione Di Ematologia Ospedale Cattedra di Ematologia	Rome		Italy	00144
57	Azienda Policlinico Umberto I, Universita La Sapienzadi Roma	Rome		Italy	00161
58	Dipartimento di Onco-Ematologia	San Giovanni Rotondo (FG)		Italy	71013
59	Azienda Sanitaria Ospedaliera Molinette S. Giovanni Battista	Turin		Italy	10126
60	VU Medical Center	Amsterdam		Netherlands	1081 HV
61	Erasmus Medical Center	Rotterdam		Netherlands	3015 GD/3000 CA
62	Erasmus Medisch Centrum	Rotterdam		Netherlands	3015 GD
63	Universitair Medisch Centrum Utrecht	Utrecht		Netherlands
64	Klinika Hematologii Samodzielny Publiczny Szpital Kliniczny Akademii	Bialystok		Poland	15-276
65	Institute of Internal Diseases University of Medicine	Gdansk		Poland	80-211
66	Oddzial Kliniczny Kliniki Hematologii	Krakow		Poland	31-501
67	Uniwersytet Medyczny w Lodzi	Lodz		Poland	93-509
68	University School of Medicine	Lublin		Poland	20-290
69	Akademia Medyczna w Warszawie Samodzielny Publiczny Centralny Szpital Kliniczny	Warsaw		Poland	02-097
70	Burdenko Central Military Clinical Hospital	Moscow		Russian Federation	105229
71	Institution of Russian Academy of Medical Sciences Russian Oncological Research Centre n.a. N. N. Bl	Moscow		Russian Federation	115678
72	Moscow Regional Research Institute n.a. Vladimirsky	Moscow		Russian Federation	129110
73	Novosibirsk State Regional Clinical Hospital	Novosibirsk		Russian Federation	630087
74	Medical Radiological Research Center RAMS	Obninsk		Russian Federation	249036
75	Samara Regional Clinical Hospital	Samara		Russian Federation	443095
76	St. Petersburg Research Institute of Hematology and Blood Transfusion	St. Petersburg		Russian Federation	191024
77	Hospital Clinic	Barcelona		Spain	08036
78	Hospital Universitaro Puerta del MarServicio de Hematologia	Cadiz		Spain	11009
79	Hospital Universitario de la Princessa	Madrid		Spain	28006
80	Hospital Universitario de Salamanca	Salamanca		Spain	37007
81	Hospital Virgen del Rocio Servicio de Hematologia	Sevilla		Spain	41013
82	Medicinkliniken	Boras		Sweden	501 82
83	Medicinska kliniken	Malmö		Sweden	20502
84	UniversitatsSpital ZurichKlinik fur Onkologie	Zurich		Switzerland	CH-8091
85	Ankara University	Ankara		Turkey	06620
86	Marmara School of Medicine	Istanbul		Turkey	34662
87	Ege University Medical School	Izmir		Turkey	35100
88	Cherkassy Regional Oncology Center	Cherkassy		Ukraine	18009
89	Dnepropetrovsk City Clinical Hospital 4	Dnepropetrovsk		Ukraine	49044
90	Institute of Urgent and Recovery Surgery	Donetsk		Ukraine	83047
91	Institute of Hematology and Transfusiology of the UAMS Department of blood diseases	Kiev		Ukraine	04060
92	Institute of Blood Pathology and Transfusion Medicine of the AMS of Ukraine	Lviv 79044		Ukraine
93	Zhitomir Regional Clinical Hospital	Zhitomir		Ukraine	10003
94	Monklands Hospital	Aidrie		United Kingdom	ML6 0JS
95	St James's University Hospital	Leeds		United Kingdom	LS7 9TF
96	University College London Hospitals Cancer Clinical Trials Unitist FloorCentral wing	London		United Kingdom	NW1 2PG
97	Kings College Hospital	London		United Kingdom	SE5 9RS
98	Christie NHS Trust Hospital	Manchester		United Kingdom	M20 4BX

Sponsors and Collaborators

• Celgene Corporation

Investigators

• Principal Investigator: Antonio Palumbo, M.D., Azienda Sanitaria Ospedaliera Molinette S. Giovanni Battista

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Celgene Corporation
• ClinicalTrials.gov Identifier: NCT00405756
• Other Study ID Numbers: CC-5013-MM-015; 2006-001865-41
• First Posted: Nov 30, 2006
• Last Update Posted: Jan 11, 2017
• Last Verified: Nov 1, 2016

• Keywords provided by Celgene Corporation: Newly Diagnosed Multiple Myeloma; Celgene; CC-5013; Revlimid; Lenalidomide; Melphalan; Prednisone; Elderly
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Aspirin; Prednisone; Lenalidomide; Melphalan

Study Results

Participant Flow

Recruitment Details	Data represents a May 11, 2010 data cut-off. The study is ongoing.
Pre-assignment Detail	Of the 606 subjects screened for this study, 147 failed screening. Reasons for screen failures included: laboratory values not met (45 subjects); diagnostic criteria for measurable multiple myeloma not met (30 subjects); other inclusion/exclusion criteria not met (30 subjects); subject withdrawal of consent (14 subjects); and other (28 subjects).

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Period Title: Double-blind Treatment
STARTED	152	153	154
Safety Population	150	152	153
COMPLETED	0	0	0
NOT COMPLETED	152	153	154
Period Title: Double-blind Treatment
STARTED	19	47	72
COMPLETED	0	0	0
NOT COMPLETED	19	47	72
Period Title: Double-blind Treatment
STARTED	75	90	88
COMPLETED	0	0	0
NOT COMPLETED	75	90	88

Baseline Characteristics

Arm/Group Title	MPR+R	MPR+p	MPp+p	Total
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Total of all reporting groups
Overall Participants	152	153	154	459
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	72.0 (5.33)	72.1 (5.20)	72.0 (5.26)	72.0 (5.25)
Age, Customized (participants) [Number]
<=75 years	116 76.3%	116 75.8%	116 75.3%	348 75.8%
>75 years	36 23.7%	37 24.2%	38 24.7%	111 24.2%
Gender (Count of Participants)
Female	81 53.3%	71 46.4%	79 51.3%	231 50.3%
Male	71 46.7%	82 53.6%	75 48.7%	228 49.7%
Race/Ethnicity, Customized (participants) [Number]
White	151 99.3%	151 98.7%	151 98.1%	453 98.7%
Black	1 0.7%	0 0%	0 0%	1 0.2%
Hispanic	0 0%	0 0%	1 0.6%	1 0.2%
Asian / Pacific Islander	0 0%	0 0%	0 0%	0 0%
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Other	0 0%	2 1.3%	2 1.3%	4 0.9%
Weight (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	73.5 (14.77)	72.0 (12.79)	72.1 (15.20)	72.5 (14.28)
Height (centimeter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter]	164.8 (9.81)	165.3 (9.33)	165.7 (9.79)	165.3 (9.63)
Systolic Blood Pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	133.9 (17.71)	135.5 (18.60)	136.4 (20.13)	135.3 (18.83)
Diastolic Blood Pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	78.5 (9.53)	77.4 (9.99)	78.8 (10.40)	78.2 (9.98)
Temperature (degrees centigrade) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [degrees centigrade]	36.5 (0.41)	36.5 (0.38)	36.5 (0.40)	36.5 (0.40)
Pulse (beats per minute) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [beats per minute]	76.0 (9.77)	77.3 (10.50)	76.3 (10.80)	76.5 (10.36)
Karnofsky Performance Scale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	81.1 (11.95)	82.2 (11.71)	84.0 (11.46)	82.4 (11.74)
International Staging System (ISS) (participants) [Number]
Stage I	28 18.4%	32 20.9%	28 18.2%	88 19.2%
Stage II	50 32.9%	47 30.7%	48 31.2%	145 31.6%
Stage III	74 48.7%	74 48.4%	78 50.6%	226 49.2%
Creatinine clearance (participants) [Number]
>=60 ml/min	72 47.4%	83 54.2%	77 50%	232 50.5%
<60 ml/min	78 51.3%	69 45.1%	76 49.4%	223 48.6%
Missing	2 1.3%	1 0.7%	1 0.6%	4 0.9%
Beta2 Microglobulin (participants) [Number]
>5.5 mg/L	74 48.7%	78 51%	67 43.5%	219 47.7%
<=5.5 mg/L	77 50.7%	75 49%	87 56.5%	239 52.1%
Missing	1 0.7%	0 0%	0 0%	1 0.2%
Albumin (participants) [Number]
>35 g/L	87 57.2%	82 53.6%	81 52.6%	250 54.5%
<= 35 g/L	63 41.4%	70 45.8%	72 46.8%	205 44.7%
Missing	2 1.3%	1 0.7%	1 0.6%	4 0.9%
C-reactive Protein (participants) [Number]
>4 mg/L	65 42.8%	56 36.6%	64 41.6%	185 40.3%
<=4 mg/L	84 55.3%	94 61.4%	89 57.8%	267 58.2%
Missing	3 2%	3 2%	1 0.6%	7 1.5%
Multiple Myeloma Subtype (participants) [Number]
Immunoglobulin A (IgA)	39 25.7%	38 24.8%	33 21.4%	110 24%
Other	108 71.1%	112 73.2%	116 75.3%	336 73.2%
Missing	5 3.3%	3 2%	5 3.2%	13 2.8%
Plasma Cells in the Bone Marrow (percentage of plasma cells) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of plasma cells]	39.8 (24.79)	39.3 (25.01)	37.9 (23.65)	39.0 (24.45)

Outcome Measures

1. Primary Outcome

Title	Kaplan Meier Estimates of Progression-free Survival (PFS) Based on the Response Assessment by the Central Adjudication Committee (CAC)
Description	Data as of 11 May 2010 cutoff. PFS was calculated as the time from randomization to the earlier of the first documentation of progressive disease (PD) as determined by the CAC, or death on study due to any cause. PD was based on the European Group for Blood and Marrow Transplantation/International Bone Marrow Transplant Registry/Autologous Bone Marrow Transplant Registry [EBMT/IBMTR/ABMTR] criteria. PD criteria includes increasing monoclonal paraprotein levels, bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.
Time Frame	up to 165 weeks

Outcome Measure Data

Analysis Population Description

Intent-to-treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Measure Participants	152	153	154
Median (95% Confidence Interval) [weeks]	136.1	62.1	56.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MPR+R, MPp+p
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	The p-value is based on unstratified log rank test of Kaplan-Meier curve differences between the treatment groups.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.395
	Confidence Interval	(2-Sided) 95%; 0.278 to 0.560
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MPR+R, MPR+p
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	The p-value is based on unstratified log rank test of Kaplan-Meier curve differences between the treatment groups.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.494
	Confidence Interval	(2-Sided) 95%; 0.347 to 0.702
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MPR+p, MPp+p
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.134
	Comments	The p-value is based on unstratified log rank test of Kaplan-Meier curve differences between the treatment groups.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.796
	Confidence Interval	(2-Sided) 95%; 0.589 to 1.075
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Kaplan Meier Estimates of Progression-free Survival (PFS) From Start of Maintenance Therapy Period Based on the Response Assessment by the Central Adjudication Committee (CAC)
Description	Data as of 11 May 2010 cutoff. PFS calculated from the start of the Maintenance period to the earlier of the first documentation of progressive disease (PD) as determined by the CAC, or death on study due to any cause. PD was based on the European Group for Blood and Marrow Transplantation/International Bone Marrow Transplant Registry/Autologous Bone Marrow Transplant Registry [EBMT/IBMTR/ABMTR] criteria. PD criteria includes increasing monoclonal paraprotein levels, bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.
Time Frame	Approximately week 37 (start of cycle 10) to week 165

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) population of participants in Arms MPR+R and MPR+p who entered maintenance within the Double-blind Treatment Period

Arm/Group Title	MPR+R	MPR+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Measure Participants	88	94
Median (95% Confidence Interval) [weeks]	112.0	32.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MPR+R, MPR+p
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Log Rank
	Comments	P-value is based on unstratified log rank test of Kaplan-Meier curve differences between the treatment groups.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.340
	Confidence Interval	(2-Sided) 95%; 0.214 to 0.541
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Kaplan Meier Estimates of Overall Survival (OS)
Description	Data as of 11 May 2010 cutoff. Overall survival (OS) was defined as the time between randomization and death. Participants who died, regardless of the cause of death, were considered to have had an event. Participants who were lost to follow-up prior to the end of the trial, or who were withdrawn from the trial, were censored at the time of last contact. Participants who were still being treated were censored at the last available date available, or clinical cut-off date, if it was earlier.
Time Frame	up to 177 weeks

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Measure Participants	152	153	154
Median (95% Confidence Interval) [weeks]	NA	NA	NA

4. Secondary Outcome

Title	Kaplan Meier Estimates of Time to Progression (TTP) Based on the Response Assessment by the Central Adjudication Committee (CAC)
Description	Data as of 11 May 2010 cutoff. TTP was the time between randomization and disease progression as determined by the CAC. PD was based on the European Group for Blood and Marrow Transplantation/International Bone Marrow Transplant Registry/Autologous Bone Marrow Transplant Registry [EBMT/IBMTR/ABMTR] criteria. PD criteria includes increasing monoclonal paraprotein levels, bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.
Time Frame	up to 165 weeks

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Measure Participants	152	153	154
Median (95% Confidence Interval) [weeks]	148.1	62.7	61.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MPR+R, MPp+p
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	The p-value is based on unstratified log rank test of Kaplan-Meier curve differences between the treatment groups.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.337
	Confidence Interval	(2-Sided) 95%; 0.231 to 0.493
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MPR+R, MPR+p
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	The p-value is based on unstratified log rank test of Kaplan-Meier curve differences between the treatment groups.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.414
	Confidence Interval	(2-Sided) 95%; 0.284 to 0.603
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MPR+p, MPp+p
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.223
	Comments	The p-value is based on unstratified log rank test of Kaplan-Meier curve differences between the treatment groups.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.826
	Confidence Interval	(2-Sided) 95%; 0.606 to 1.125
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Number of Participants in Disease Response Categories Representing Their Best Response During the Double-blind Treatment Period
Description	Data as of 11 May 2010 cutoff. Best response was determined by the Central Assessment Committee (CAC) based on the European Group for Blood and Marrow Transplantation (EBMT) criteria: Complete Response (CR)-absence of serum and urine monoclonal paraprotein for 6 weeks, plus no increase in size or number of bone lesions, plus other factors); Partial Response (PR)-not all CR criteria, plus >=50% reduction in serum monoclonal paraprotein plus others; Stable Disease (SD)- not PR or PD; Progressive Disease (PD)- reappearance of monoclonal paraprotein, bone lesions, other; Not Evaluable (NE).
Time Frame	Up to 165 weeks

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Measure Participants	152	153	154
Complete response (CR)	15 9.9%	5 3.3%	5 3.2%
Partial response (PR)	102 67.1%	99 64.7%	72 46.8%
Stable disease (SD)	28 18.4%	40 26.1%	70 45.5%
Progressive disease (PD)	0 0%	2 1.3%	0 0%
Response not evaluable (NE)	7 4.6%	7 4.6%	7 4.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MPR+R, MPp+p
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value calculation excludes the category - Response not evaluable (NE)
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MPR+R, MPR+p
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments	P-value calculation excludes the category - Response not evaluable (NE)
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MPR+p, MPp+p
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments	P-value calculation excludes the category - Response not evaluable (NE)
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	MPR+R, MPp+p
	Comments	Based on dichotomized response: 1) CR or PR 2) SD or PD or NE
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.34
	Confidence Interval	(2-Sided) 95%; 2.04 to 5.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	MPR+R, MPR+p
	Comments	Based on dichotomized response: 1) CR or PR 2) SD or PD or NE
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.096
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.58
	Confidence Interval	(2-Sided) 95%; 0.95 to 2.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	MPR+p, MPp+p
	Comments	Based on dichotomized response: 1) CR or PR 2) SD or PD or NE
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.12
	Confidence Interval	(2-Sided) 95%; 1.33 to 3.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Time to First Response
Description	Data as of 11 May 2010 cutoff. Time to first response was defined as the time from start of treatment until first response as assessed by the Central Assessment Committee (CMC) based on European Group for Blood and Marrow Transplantation (EBMT) criteria.
Time Frame	Up to 66 weeks

Outcome Measure Data

Analysis Population Description

Participants who had a partial response (PR) or complete response (CR)

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Measure Participants	117	104	77
Mean (Standard Deviation) [weeks]	10.0 (7.40)	9.3 (6.55)	16.2 (11.59)

7. Secondary Outcome

Title	Kaplan Meier Estimates for Duration of Response as Determined by the Central Adjudication Committee (CAC)
Description	Data as of 11 May 2010 cutoff. Duration of myeloma response was defined as the time from the initial response date to the earlier of progressive disease (PD) as determined by the CAC or death on study. PD was based on the European Group for Blood and Marrow Transplantation/International Bone Marrow Transplant Registry/Autologous Bone Marrow Transplant Registry [EBMT/IBMTR/ABMTR] criteria. PD criteria includes increasing monoclonal paraprotein levels, bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.
Time Frame	Up to 149 weeks

Outcome Measure Data

Analysis Population Description

Population: Participants who achieved a partial response (PR) or complete response (CR).

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Measure Participants	117	104	77
Median (95% Confidence Interval) [weeks]	121.6	56.1	55.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MPR+R, MPp+p
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	The p-value is based on unstratified log rank test of Kaplan Meier curve differences between the treatment groups.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.348
	Confidence Interval	(2-Sided) 95%; 0.228 to 0.531
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MPR+R, MPR+p
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	The p-value is based on unstratified log rank test of Kaplan Meier curve differences between the treatment groups.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.419
	Confidence Interval	(2-Sided) 95%; 0.281 to 0.623
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MPR+p, MPp+p
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.302
	Comments	The p-value is based on unstratified log rank test of Kaplan Meier curve differences between the treatment groups.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.825
	Confidence Interval	(2-Sided) 95%; 0.571 to 1.191
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Kaplan Meier Estimates for Time to Next Antimyeloma Therapy
Description	Data as of 11 May 2010 cutoff. Time to the next antimyeloma therapy was defined as time from randomization to the start of another non-protocol antimyeloma therapy. Participants who do not receive another anti-myeloma therapy were censored at the last assessment or follow-up visit known to have received no new therapy.
Time Frame	Up to 168 weeks

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Measure Participants	152	153	154
Median (95% Confidence Interval) [weeks]	128.9	66.1	66.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MPR+R, MPp+p
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	The p-value is based on unstratified log rank test of Kaplan Meier curve differences between the treatment groups.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.404
	Confidence Interval	(2-Sided) 95%; 0.296 to 0.553
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MPR+R, MPR+p
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	The p-value is based on unstratified log rank test of Kaplan Meier curve differences between the treatment groups.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.499
	Confidence Interval	(2-Sided) 95%; 0.363 to 0.688
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MPR+p, MPp+p
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.169
	Comments	The p-value is based on unstratified log rank test of Kaplan Meier curve differences between the treatment groups.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.827
	Confidence Interval	(2-Sided) 95%; 0.630 to 1.085
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period
Description	Data as of 11 May 2010 cutoff. Participant counts in different categories of TEAEs during the double-blind treatment period. A TEAE is as any AE occurring or worsening on or after the first treatment of any study drug, and within 30 days after the last dose of the last study drug. Severity grades according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE) on a 1-5 scale: Grade 1= Mild AE, Grade 2= Moderate AE, Grade 3= Severe AE, Grade 4= Life-threatening or disabling AE, Grade 5=Death related to AE. Dose reduction includes reduction with or without interruption.
Time Frame	Up to 169 weeks (Double-blind therapy period plus 4 weeks)

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Measure Participants	150	152	153
>=1 adverse event (AE)	150 98.7%	151 98.7%	153 99.4%
>=1 CTCAE grade 3-4 AE	137 90.1%	129 84.3%	107 69.5%
>=1 CTCAE grade 5 AE	7 4.6%	6 3.9%	7 4.5%
>=1 serious AE (SAE)	66 43.4%	62 40.5%	56 36.4%
>=1 AE related to Lenaldomide/Placebo	148 97.4%	145 94.8%	131 85.1%
>=1 AE related to Melphalan	140 92.1%	134 87.6%	126 81.8%
>=1AE related to Prednisone	87 57.2%	94 61.4%	93 60.4%
>=1 Grade 3-4 AE related to Lenaldomide/Placebo	128 84.2%	117 76.5%	68 44.2%
>=1 Grade 3-4 AE related to Melphalan	118 77.6%	110 71.9%	62 40.3%
>=1 Grade 3-4 AE related to Prednisone	32 21.1%	29 19%	22 14.3%
>=1 Grade 5 AE related to Lenalidomide/Placebo	3 2%	2 1.3%	2 1.3%
>=1 Grade 5 AE related to Melphalan	3 2%	1 0.7%	3 1.9%
>=1 Grade 5 AE related to Prednisone	1 0.7%	1 0.7%	1 0.6%
>=1 SAE related to Lenalidomide/Placebo	38 25%	32 20.9%	11 7.1%
>=1 SAE related to Melphalan	27 17.8%	24 15.7%	11 7.1%
>=1 SAE related to Prednisone	19 12.5%	16 10.5%	5 3.2%
>=1 AE leading to Lenalidomide/Placebo withdrawal	26 17.1%	24 15.7%	14 9.1%
>=1 AE leading to Melphalan withdrawal	20 13.2%	19 12.4%	10 6.5%
>=1 AE leading to Prednisone withdrawal	20 13.2%	19 12.4%	10 6.5%
>=1 AE leading to Lenalidomide/Plac dose reduction	71 46.7%	70 45.8%	26 16.9%
>=1 AE leading to Melphalan dose reduction	47 30.9%	58 37.9%	21 13.6%
>=1 AE leading to Prednisone dose reduction	15 9.9%	7 4.6%	5 3.2%
>=1 AE leading to Lenalidomide/Plac dose interrupt	92 60.5%	82 53.6%	51 33.1%
>=1 AE leading to Melphalan dose interruption	5 3.3%	1 0.7%	0 0%
>=1 AE leading to Prednisone dose interruption	28 18.4%	39 25.5%	15 9.7%

10. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Quality of Life Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLC-C30 is a 30-item questionnaire to assess the quality of life in cancer patients. EORTC QLQ-C30 includes functional scales (physical, role, cognitive, emotional, social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and other (dyspnoea, appetite loss, insomnia, constipation/diarrhea, financial difficulties). Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); two used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better quality of life.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Measure Participants	152	153	154
Cycle 4 - approximately Month 4 (n=114,121,125)	2.3 (26.13)	5.6 (18.86)	6.1 (19.41)
Cycle 7 - approximately Month 7 (n=96,108,110)	8.0 (24.95)	8.1 (22.48)	4.2 (23.92)
Cycle 10 - approximately Month 10 (n=84,86,96)	12.4 (25.33)	8.8 (24.70)	6.2 (24.60)
Cycle 13 - approximately Month 13 (n=70,70,82)	7.6 (28.32)	8.8 (24.02)	5.4 (22.80)
Cycle 16 - approximately Month 16 (n=61,50,62)	10.7 (25.28)	7.2 (26.29)	8.1 (25.11)

11. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Physical Functioning Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score=better level of physical functioning.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Measure Participants	152	153	154
Cycle 4 - approximately Month 4 (n=120,127,130)	1.9 (23.72)	3.3 (21.64)	4.5 (18.68)
Cycle 7 - approximately Month 7 (n=100,112,112)	8.2 (22.71)	8.1 (20.54)	2.7 (23.20)
Cycle 10 - approximately Month 10 (n=88,95,96)	8.9 (22.75)	8.5 (25.62)	5.1 (20.42)
Cycle 13 - approximately Month 13 (n=75,74,83)	8.6 (24.04)	9.7 (25.39)	3.3 (20.30)
Cycle 16 - approximately Month 16 (n=64,53,63)	10.0 (25.00)	7.6 (22.66)	1.1 (19.30)

12. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Role Functioning Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score=better level of role functioning.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Measure Participants	152	153	154
Cycle 4 - approximately Month 4 (n=119,127,130)	1.8 (33.18)	3.0 (30.75)	7.4 (26.34)
Cycle 7 - approximately Month 7 (n=99,112,113)	5.7 (35.57)	8.0 (32.42)	6.9 (31.16)
Cycle 10 - approximately Month 10 (n=86,95,95)	9.3 (35.76)	7.5 (36.29)	5.6 (31.29)
Cycle 13 - approximately Month 13 (n=74,74,82)	9.7 (40.36)	11.7 (33.42)	5.7 (30.68)
Cycle 16 - approximately Month 16 (n=64,53,63)	12.2 (40.09)	8.5 (34.22)	7.1 (31.93)

13. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Emotional Functioning Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better level of emotional functioning.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Measure Participants	152	153	154
Cycle 4 - approximately Month 4 (n=115,125,128)	4.8 (25.00)	2.7 (22.59)	6.8 (18.75)
Cycle 7 - approximately Month 7 (n=98,111,112)	8.8 (24.94)	4.2 (20.38)	5.0 (21.56)
Cycle 10 - approximately Month 10 (n=86,92,97)	9.0 (23.28)	1.6 (22.07)	4.7 (22.05)
Cycle 13 - approximately Month 13 (n=73,73,83)	8.2 (24.59)	1.1 (21.78)	6.6 (21.78)
Cycle 16 - approximately Month 16 (n=63,52,63)	9.9 (23.23)	-0.2 (21.57)	6.9 (19.72)

14. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Congitive Functioning Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better level of cognitive functioning.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Measure Participants	152	153	154
Cycle 4 - approximately Month 4 (n=115,125,128)	0.3 (21.51)	-2.0 (21.33)	1.3 (16.68)
Cycle 7 - approximately Month 7 (n=98,111,113)	2.9 (22.31)	0.1 (17.33)	0.7 (18.42)
Cycle 10 - approximately Month 10 (n=87,92,97)	1.0 (22.64)	-4.4 (19.89)	-2.7 (20.65)
Cycle 13 - approximately Month 13 (n=73,73,83)	-0.0 (21.34)	-3.0 (23.78)	-1.4 (17.69)
Cycle 16 - approximately Month 16 (n=63,52,63)	0.3 (22.29)	-3.5 (27.48)	-4.0 (18.13)

15. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Social Functioning Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better level of social functioning.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Measure Participants	152	153	154
Cycle 4 - approximately Month 4 (n=115,125,127)	5.1 (35.05)	0.3 (26.60)	6.0 (22.78)
Cycle 7 - approximately Month 7 (n=98,111,112)	8.3 (33.87)	4.4 (24.48)	6.1 (26.57)
Cycle 10 - approximately Month 10 (n=87,92,97)	10.9 (34.27)	4.5 (29.87)	4.1 (27.22)
Cycle 13 - approximately Month 13 (n=72,73,83)	11.8 (32.91)	7.5 (29.80)	6.2 (27.63)
Cycle 16 - approximately Month 16 (n=63,52,63)	13.2 (33.35)	6.1 (30.79)	9.8 (28.66)

16. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the fatigue scale = higher level of symptomatology/problems.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Measure Participants	152	153	154
Cycle 4 - approximately Month 4 (n=120,127,129)	-3.0 (25.61)	-5.5 (24.08)	-5.1 (24.33)
Cycle 7 - approximately Month 7 (n=100,112,110)	-7.6 (23.00)	-9.5 (25.97)	-5.7 (27.32)
Cycle 10 - approximately Month 10 (n=87,95,95)	-7.5 (27.31)	-7.5 (29.78)	-6.9 (28.31)
Cycle 13 - approximately Month 13 (n=74,74,82)	-7.1 (26.08)	-10.7 (30.33)	-7.5 (27.29)
Cycle 16 - approximately Month 16 (n=64,53,62)	-10.0 (26.86)	-9.7 (28.77)	-4.1 (26.34)

17. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Nausea and Vomiting Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the nausea/vomiting scale = higher level of symptomatology/problems.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Measure Participants	152	153	154
Cycle 4 - approximately Month 4 (n=120,127,130)	3.3 (19.40)	-1.3 (17.14)	-0.0 (17.36)
Cycle 7 - approximately Month 7 (n=99,112,112)	0.5 (14.57)	-0.7 (19.94)	0.7 (14.73)
Cycle 10 - approximately Month 10 (n=87,95,97)	1.9 (16.75)	-1.4 (19.40)	0.3 (14.23)
Cycle 13 - approximately Month 13 (n=75,72,83)	0.7 (13.55)	-3.0 (19.65)	-0.4 (12.48)
Cycle 16 - approximately Month 16 (n=64,52,62)	1.0 (12.90)	-4.2 (18.65)	-1.3 (9.21)

18. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Pain Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the pain scale = higher level of symptomatology/problems.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Measure Participants	152	153	154
Cycle 4 - approximately Month 4 (n=120,127,129)	-14.4 (32.76)	-13.8 (33.60)	-13.4 (29.32)
Cycle 7 - approximately Month 7 (n=100,112,113)	-17.8 (36.18)	-16.5 (33.45)	-11.5 (33.49)
Cycle 10 - approximately Month 10 (n=88,95,97)	-17.2 (34.78)	-15.6 (35.30)	-9.8 (31.71)
Cycle 13 - approximately Month 13 (n=74,74,83)	-13.7 (40.48)	-14.9 (33.28)	-12.1 (27.46)
Cycle 16 - approximately Month 16 (n=64,53,63)	-20.3 (33.92)	-11.0 (33.00)	-12.2 (29.96)

19. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Dyspnoea Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the dyspnoea scale = higher level of symptomatology/problems.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Measure Participants	152	153	154
Cycle 4 - approximately Month 4 (n=117,126,126)	-2.6 (29.74)	-6.4 (32.04)	-0.0 (23.48)
Cycle 7 - approximately Month 7 (n=100,110,110)	-1.7 (28.18)	-8.5 (32.07)	2.1 (20.82)
Cycle 10 - approximately Month 10 (n=86,93,96)	-4.3 (30.60)	-4.3 (35.87)	3.8 (25.07)
Cycle 13 - approximately Month 13 (n=73,73,81)	-5.0 (30.26)	-2.3 (30.60)	-0.0 (22.35)
Cycle 16 - approximately Month 16 (n=62,53,62)	-3.2 (29.39)	-6.3 (32.07)	1.6 (22.92)

20. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Insomnia Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the insomnia scale = higher level of symptomatology/problems.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Measure Participants	152	153	154
Cycle 4 - approximately Month 4 (n=118,124,128)	2.0 (33.56)	-1.6 (31.77)	-5.0 (27.77)
Cycle 7 - approximately Month 7 (n=100,109,111)	-1.0 (29.76)	-6.4 (27.02)	-5.7 (32.06)
Cycle 10 - approximately Month 10 (n=87,94,96)	-5.0 (28.99)	-2.5 (25.04)	-1.7 (32.58)
Cycle 13 - approximately Month 13 (n=75,73,83)	-4.9 (29.86)	0.9 (29.38)	-6.8 (29.80)
Cycle 16 - approximately Month 16 (n=64,53,63)	-4.7 (32.46)	-0.6 (32.36)	-3.7 (31.18)

21. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Appetite Loss Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the appetite loss scale = higher level of symptomatology/problems.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Measure Participants	152	153	154
Cycle 4 - approximately Month 4 (n=119,125,130)	1.7 (36.54)	1.9 (34.73)	-5.6 (25.96)
Cycle 7 - approximately Month 7 (n=99,111,111)	-3.7 (33.64)	-5.7 (31.75)	-5.7 (27.66)
Cycle 10 - approximately Month 10 (n=87,93,96)	-5.0 (33.15)	-5.4 (29.20)	-8.0 (29.32)
Cycle 13 - approximately Month 13 (n=75,72,83)	-6.2 (36.23)	-8.8 (30.13)	-4.8 (32.15)
Cycle 16 - approximately Month 16 (n=64,52,63)	-7.8 (36.01)	-16.0 (35.24)	-6.4 (28.62)

22. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Constipation Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the constipation scale = higher level of symptomatology/problems.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Measure Participants	152	153	154
Cycle 4 - approximately Month 4 (n=114,124,128)	-1.8 (34.31)	4.8 (30.86)	-4.9 (27.45)
Cycle 7 - approximately Month 7 (n=96,111,112)	-3.5 (36.35)	0.6 (30.14)	-2.7 (31.05)
Cycle 10 - approximately Month 10 (n=86,93,97)	-5.0 (34.88)	-1.1 (28.43)	-1.7 (26.95)
Cycle 13 - approximately Month 13 (n=73,73,81)	-5.0 (31.27)	-2.7 (28.74)	-3.3 (29.16)
Cycle 16 - approximately Month 16 (n=63,51,62)	-1.6 (31.36)	-5.2 (30.82)	-2.2 (32.44)

23. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Diarrhoea Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the diarrhea scale = higher level of symptomatology/problems.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Measure Participants	152	153	154
Cycle 4 - approximately Month 4 (n=115,125,124)	2.3 (28.85)	1.9 (24.06)	3.2 (25.65)
Cycle 7 - approximately Month 7 (n=98,109,112)	3.4 (25.54)	-1.2 (23.09)	0.9 (22.13)
Cycle 10 - approximately Month 10 (n=87,92,95)	1.1 (22.98)	1.4 (20.91)	-0.0 (21.19)
Cycle 13 - approximately Month 13 (n=73,73,80)	5.5 (30.43)	-1.4 (18.78)	0.8 (18.35)
Cycle 16 - approximately Month 16 (n=63,52,61)	10.6 (35.83)	1.3 (19.75)	0.5 (17.74)

24. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Financial Difficulties Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a problem scale like the financial problems scale = higher level of financial problems.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Measure Participants	152	153	154
Cycle 4 - approximately Month 4 (n=111,123,125)	2.4 (24.91)	-1.1 (19.06)	-2.9 (18.93)
Cycle 7 - approximately Month 7 (n=94,111,112)	2.1 (23.85)	-0.6 (28.07)	-2.1 (22.50)
Cycle 10 - approximately Month 10 (n=84,92,97)	6.0 (21.44)	0.7 (28.81)	-1.7 (19.47)
Cycle 13 - approximately Month 13 (n=70,72,83)	4.8 (21.45)	-0.5 (28.80)	-4.0 (26.75)
Cycle 16 - approximately Month 16 (n=61,52,63)	1.6 (20.58)	-0.6 (35.24)	-5.3 (30.06)

25. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. EORTC QLQ-MY20 includes four scales: disease symptoms, treatment side-effects, future perspective, and body image. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale; higher score for the disease symptoms scale = higher level of symptomatology.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Measure Participants	152	153	154
Cycle 4 - approximately Month 4 (n=113,121,127)	-8.9 (19.56)	-8.7 (19.13)	-5.4 (15.83)
Cycle 7 - approximately Month 7 (n=96,109,112)	-9.0 (20.64)	-9.7 (23.25)	-6.0 (20.81)
Cycle 10 - approximately Month 10 (n=85,91,95)	-7.9 (23.00)	-7.1 (23.85)	-5.4 (18.79)
Cycle 13 - approximately Month 13 (n=72,73,82)	-7.2 (25.91)	-8.8 (24.90)	-6.3 (21.84)
Cycle 16 - approximately Month 16 (n=62,51,62)	-10.5 (23.87)	-5.9 (25.79)	-3.3 (20.67)

26. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Side Effects of Treatment Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale; higher score for the side effects scale = higher level of symptomatology.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Measure Participants	152	153	154
Cycle 4 - approximately Month 4 (n=113,120,125)	1.3 (13.37)	0.1 (13.28)	0.6 (12.67)
Cycle 7 - approximately Month 7 (n=95,108,111)	0.4 (15.22)	-1.7 (14.27)	1.8 (12.94)
Cycle 10 - approximately Month 10 (n=85,89,94)	-1.6 (14.46)	0.0 (15.99)	0.3 (12.61)
Cycle 13 - approximately Month 13 (n=72,72,81)	-3.8 (15.61)	-1.0 (14.59)	0.3 (12.60)
Cycle 16 - approximately Month 16 (n=62,50,61)	-2.1 (14.95)	-2.9 (14.16)	-0.9 (12.23)

27. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Future Perspective Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale. For the future perspective scale, higher score = better perspective of the future.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Measure Participants	152	153	154
Cycle 4 - approximately Month 4 (n=112,121,124)	4.7 (23.74)	4.3 (23.56)	7.6 (22.38)
Cycle 7 - approximately Month 7 (n=93,108,112)	14.6 (24.45)	7.7 (23.86)	9.8 (20.62)
Cycle 10 - approximately Month 10 (n=83,88,97)	17.3 (27.84)	6.6 (22.40)	14.5 (21.73)
Cycle 13 - approximately Month 13 (n=71,73,81)	17.3 (27.15)	6.3 (23.78)	11.9 (24.67)
Cycle 16 - approximately Month 16 (n=62,52,62)	18.5 (25.30)	7.7 (28.49)	14.4 (26.62)

28. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Body Image Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale. For the body image scale, higher scores = better body image.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Measure Participants	152	153	154
Cycle 4 - approximately Month 4 (n=110,117,119)	2.1 (35.36)	-0.3 (37.27)	4.5 (25.65)
Cycle 7 - approximately Month 7 (n=88,104,108)	3.8 (33.32)	2.6 (37.94)	5.2 (27.78)
Cycle 10 - approximately Month 10 (n=79,83,94)	7.6 (33.32)	-4.0 (43.69)	3.9 (26.72)
Cycle 13 - approximately Month 13 (n=68,72,79)	1.0 (31.01)	-0.5 (44.23)	5.1 (32.51)
Cycle 16 - approximately Month 16 (n=59,52,61)	3.4 (32.58)	6.4 (41.25)	2.7 (28.08)

Adverse Events

Time Frame	Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Arm/Group Title	MPR+R		MPR+p		MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.		Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.		Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
All Cause Mortality
	MPR+R		MPR+p		MPp+p
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	MPR+R		MPR+p		MPp+p
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	66/150 (44%)		62/152 (40.8%)		56/153 (36.6%)
Blood and lymphatic system disorders
Anaemia	5/150 (3.3%)	5	8/152 (5.3%)	10	2/153 (1.3%)	2
Febrile neutropenia	9/150 (6%)	9	2/152 (1.3%)	2	0/153 (0%)	0
Neutropenia	6/150 (4%)	6	4/152 (2.6%)	5	1/153 (0.7%)	1
Thrombocytopenia	2/150 (1.3%)	2	4/152 (2.6%)	4	1/153 (0.7%)	1
Pancytopenia	1/150 (0.7%)	1	2/152 (1.3%)	2	1/153 (0.7%)	1
Leukopenia	0/150 (0%)	0	1/152 (0.7%)	1	1/153 (0.7%)	1
Haemolytic anaemia	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Cardiac disorders
Atrial fibrillation	1/150 (0.7%)	1	3/152 (2%)	3	5/153 (3.3%)	6
Angina pectoris	1/150 (0.7%)	1	0/152 (0%)	0	2/153 (1.3%)	3
Bradycardia	1/150 (0.7%)	1	0/152 (0%)	0	2/153 (1.3%)	2
Cardiac failure	2/150 (1.3%)	2	0/152 (0%)	0	1/153 (0.7%)	1
Cardiogenic shock	2/150 (1.3%)	2	0/152 (0%)	0	1/153 (0.7%)	1
Palpitations	2/150 (1.3%)	3	1/152 (0.7%)	2	0/153 (0%)	0
Coronary artery disease	1/150 (0.7%)	1	1/152 (0.7%)	1	0/153 (0%)	0
Myocardial ischaemia	2/150 (1.3%)	2	0/152 (0%)	0	0/153 (0%)	0
Acute coronary syndrome	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Acute myocardial infarction	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Atrial flutter	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Cardiac arrest	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Cardiac disorder	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Coronary artery occlusion	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Right ventricular failure	0/150 (0%)	0	1/152 (0.7%)	2	0/153 (0%)	0
Sinus tachycardia	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Tachyarrhythmia	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Ear and labyrinth disorders
Vertigo	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Eye disorders
Cataract	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Retinal detachment	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Gastrointestinal disorders
Vomiting	4/150 (2.7%)	5	1/152 (0.7%)	1	3/153 (2%)	3
Nausea	3/150 (2%)	3	2/152 (1.3%)	2	2/153 (1.3%)	2
Constipation	2/150 (1.3%)	2	3/152 (2%)	3	1/153 (0.7%)	1
Diarrhoea	3/150 (2%)	3	1/152 (0.7%)	1	1/153 (0.7%)	2
Colitis	1/150 (0.7%)	1	1/152 (0.7%)	1	0/153 (0%)	0
Inguinal hernia	2/150 (1.3%)	2	0/152 (0%)	0	0/153 (0%)	0
Abdominal strangulated hernia	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Dysphagia	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Gastritis haemorrhagic	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Gastrointestinal haemorrhage	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Gastrointestinal obstruction	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Haemorrhoidal haemorrhage	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Ileus	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Melaena	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Pancreatic mass	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
General disorders
Pyrexia	6/150 (4%)	6	2/152 (1.3%)	2	7/153 (4.6%)	8
Fatigue	4/150 (2.7%)	4	2/152 (1.3%)	2	1/153 (0.7%)	1
General physical health deterioration	2/150 (1.3%)	2	1/152 (0.7%)	1	2/153 (1.3%)	2
Asthenia	0/150 (0%)	0	2/152 (1.3%)	2	1/153 (0.7%)	1
Oedema peripheral	0/150 (0%)	0	0/152 (0%)	0	2/153 (1.3%)	2
Chest pain	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Face oedema	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Malaise	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Pain	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Systemic inflammatory response syndrome	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Hepatobiliary disorders
Biliary colic	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Cholestasis	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Hepatitis toxic	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Immune system disorders
Hypersensitivity	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Infections and infestations
Pneumonia	4/150 (2.7%)	5	8/152 (5.3%)	9	8/153 (5.2%)	8
Sepsis	1/150 (0.7%)	1	3/152 (2%)	3	1/153 (0.7%)	1
Urinary tract infection	2/150 (1.3%)	2	0/152 (0%)	0	3/153 (2%)	3
Bronchitis	1/150 (0.7%)	1	2/152 (1.3%)	2	0/153 (0%)	0
Lower respiratory tract infection	2/150 (1.3%)	2	0/152 (0%)	0	1/153 (0.7%)	1
Bronchopneumonia	0/150 (0%)	0	1/152 (0.7%)	1	1/153 (0.7%)	1
Cellulitis	0/150 (0%)	0	1/152 (0.7%)	1	1/153 (0.7%)	1
Cystitis	1/150 (0.7%)	1	0/152 (0%)	0	1/153 (0.7%)	1
Diverticulitis	1/150 (0.7%)	1	0/152 (0%)	0	1/153 (0.7%)	1
Herpes zoster	1/150 (0.7%)	1	1/152 (0.7%)	1	0/153 (0%)	0
Infection	1/150 (0.7%)	1	0/152 (0%)	0	1/153 (0.7%)	1
Septic shock	1/150 (0.7%)	1	1/152 (0.7%)	1	0/153 (0%)	0
Sinusitis	2/150 (1.3%)	2	0/152 (0%)	0	0/153 (0%)	0
Upper respiratory tract infection	2/150 (1.3%)	2	0/152 (0%)	0	0/153 (0%)	0
Appendicitis	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Arthritis infective	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Bronchitis bacterial	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Campylobacter infection	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Clostridium colitis	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Erysipelas	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Escherichia infection	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Escherichia sepsis	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Gastroenteritis	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Gastroenteritis Norwalk virus	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Herpes simplex	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Lobar pneumonia	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Meningitis	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Oral candidiasis	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Post procedural infection	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Pseudomembranous colitis	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Pyelonephritis chronic	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Streptococcal bacteraemia	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Streptococcal sepsis	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Viral upper respiratory tract infection	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Injury, poisoning and procedural complications
Accidental overdose	1/150 (0.7%)	1	1/152 (0.7%)	1	0/153 (0%)	0
Femur fracture	0/150 (0%)	0	2/152 (1.3%)	2	0/153 (0%)	0
Sternal fracture	0/150 (0%)	0	0/152 (0%)	0	2/153 (1.3%)	2
Thoracic vertebral fracture	1/150 (0.7%)	1	1/152 (0.7%)	1	0/153 (0%)	0
Femoral neck fracture	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Hip fracture	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Humerus fracture	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Spinal compression fracture	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Spinal fracture	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Tendon rupture	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Therapeutic agent toxicity	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Traumatic fracture	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Fall	0/150 (0%)	0	1/152 (0.7%)	1	2/153 (1.3%)	2
Investigations
Monoclonal immunoglobulin present	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Metabolism and nutrition disorders
Dehydration	2/150 (1.3%)	2	1/152 (0.7%)	1	0/153 (0%)	0
Hypercalcaemia	2/150 (1.3%)	2	1/152 (0.7%)	1	0/153 (0%)	0
Hypocalcaemia	2/150 (1.3%)	2	1/152 (0.7%)	1	0/153 (0%)	0
Hypokalaemia	2/150 (1.3%)	2	1/152 (0.7%)	1	0/153 (0%)	0
Anorexia	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Diabetes mellitus	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Hyperglycaemia	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Hyperkalaemia	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Oral intake reduced	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Musculoskeletal and connective tissue disorders
Bone pain	3/150 (2%)	3	2/152 (1.3%)	2	6/153 (3.9%)	7
Back pain	2/150 (1.3%)	3	1/152 (0.7%)	1	1/153 (0.7%)	1
Arthralgia	1/150 (0.7%)	1	2/152 (1.3%)	2	0/153 (0%)	0
Musculoskeletal pain	2/150 (1.3%)	2	0/152 (0%)	0	1/153 (0.7%)	1
Arthropathy	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Bone lesion	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Gouty arthritis	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Intervertebral disc disorder	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Muscle haemorrhage	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Myositis	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Osteoarthritis	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Pain in extremity	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Multiple myeloma	0/150 (0%)	0	2/152 (1.3%)	2	2/153 (1.3%)	2
Leukaemia plasmacytic	0/150 (0%)	0	2/152 (1.3%)	2	1/153 (0.7%)	2
Acute myeloid leukaemia	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Bowen's disease	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Breast cancer	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Bronchial carcinoma	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Light chain disease	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Lung neoplasm malignant	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Myelodysplastic syndrome	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Plasmacytoma	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Nervous system disorders
Syncope	0/150 (0%)	0	2/152 (1.3%)	2	1/153 (0.7%)	1
Cerebral ischaemia	1/150 (0.7%)	1	1/152 (0.7%)	1	0/153 (0%)	0
Dizziness	0/150 (0%)	0	1/152 (0.7%)	1	1/153 (0.7%)	1
Aphasia	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Cerebral haemorrhage	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Cognitive disorder	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Convulsion	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Hemiparesis	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Metabolic encephalopathy	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Neuralgia	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Neuropathy peripheral	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Nystagmus	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Parkinson's disease	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Presyncope	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Syncope vasovagal	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Transient ischaemic attack	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Psychiatric disorders
Depression	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Insomnia	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Psychotic disorder due to a general medical condition	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Renal and urinary disorders
Renal failure acute	1/150 (0.7%)	1	2/152 (1.3%)	2	4/153 (2.6%)	4
Renal failure	0/150 (0%)	0	3/152 (2%)	4	2/153 (1.3%)	2
Dysuria	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Nephrotic syndrome	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	2
Renal amyloidosis	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Urinary retention	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/150 (0%)	0	0/152 (0%)	0	2/153 (1.3%)	2
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/150 (1.3%)	3	3/152 (2%)	3	2/153 (1.3%)	2
Pulmonary embolism	2/150 (1.3%)	2	3/152 (2%)	4	0/153 (0%)	0
Pleural effusion	0/150 (0%)	0	2/152 (1.3%)	3	1/153 (0.7%)	1
Respiratory failure	1/150 (0.7%)	1	1/152 (0.7%)	1	0/153 (0%)	0
Acute pulmonary oedema	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Bronchospasm	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Productive cough	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Pulmonary haemorrhage	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Skin and subcutaneous tissue disorders
Rash	0/150 (0%)	0	1/152 (0.7%)	1	1/153 (0.7%)	1
Blister	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Dermatitis exfoliative	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Drug eruption	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Erythema	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Vascular disorders
Deep vein thrombosis	1/150 (0.7%)	1	6/152 (3.9%)	7	0/153 (0%)	0
Hypertension	0/150 (0%)	0	1/152 (0.7%)	1	2/153 (1.3%)	2
Thrombosis	2/150 (1.3%)	2	1/152 (0.7%)	1	0/153 (0%)	0
Hypotension	0/150 (0%)	0	1/152 (0.7%)	1	1/153 (0.7%)	1
Aortic dissection	0/150 (0%)	0	0/152 (0%)	0	1/153 (0.7%)	1
Peripheral ischaemia	1/150 (0.7%)	1	0/152 (0%)	0	0/153 (0%)	0
Vasculitis	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Venous thrombosis	0/150 (0%)	0	1/152 (0.7%)	1	0/153 (0%)	0
Other (Not Including Serious) Adverse Events
	MPR+R		MPR+p		MPp+p
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	149/150 (99.3%)		151/152 (99.3%)		152/153 (99.3%)
Blood and lymphatic system disorders
Neutropenia	117/150 (78%)	951	116/152 (76.3%)	807	78/153 (51%)	398
Anaemia	99/150 (66%)	417	91/152 (59.9%)	351	82/153 (53.6%)	293
Thrombocytopenia	103/150 (68.7%)	514	100/152 (65.8%)	532	68/153 (44.4%)	268
Leukopenia	54/150 (36%)	418	58/152 (38.2%)	449	49/153 (32%)	237
Ear and labyrinth disorders
Vertigo	13/150 (8.7%)	23	10/152 (6.6%)	13	14/153 (9.2%)	25
Gastrointestinal disorders
Nausea	37/150 (24.7%)	65	39/152 (25.7%)	66	51/153 (33.3%)	93
Constipation	49/150 (32.7%)	80	39/152 (25.7%)	66	37/153 (24.2%)	57
Diarrhoea	43/150 (28.7%)	124	36/152 (23.7%)	62	37/153 (24.2%)	50
Vomiting	15/150 (10%)	24	18/152 (11.8%)	27	19/153 (12.4%)	30
Abdominal pain upper	13/150 (8.7%)	18	7/152 (4.6%)	9	13/153 (8.5%)	19
Abdominal pain	16/150 (10.7%)	25	9/152 (5.9%)	9	6/153 (3.9%)	7
Dyspepsia	12/150 (8%)	17	6/152 (3.9%)	6	8/153 (5.2%)	10
Dry mouth	12/150 (8%)	14	7/152 (4.6%)	8	4/153 (2.6%)	6
General disorders
Fatigue	46/150 (30.7%)	110	51/152 (33.6%)	97	57/153 (37.3%)	101
Pyrexia	32/150 (21.3%)	47	38/152 (25%)	63	27/153 (17.6%)	33
Oedema peripheral	30/150 (20%)	47	35/152 (23%)	59	25/153 (16.3%)	35
Asthenia	33/150 (22%)	67	22/152 (14.5%)	38	25/153 (16.3%)	39
Oedema	8/150 (5.3%)	11	14/152 (9.2%)	16	7/153 (4.6%)	11
Infections and infestations
Nasopharyngitis	23/150 (15.3%)	34	21/152 (13.8%)	32	26/153 (17%)	34
Upper respiratory tract infection	16/150 (10.7%)	25	19/152 (12.5%)	23	15/153 (9.8%)	20
Bronchitis	16/150 (10.7%)	25	15/152 (9.9%)	20	12/153 (7.8%)	16
Urinary tract infection	12/150 (8%)	15	11/152 (7.2%)	15	11/153 (7.2%)	13
Investigations
Blood creatinine increased	12/150 (8%)	21	6/152 (3.9%)	13	17/153 (11.1%)	33
Weight decreased	8/150 (5.3%)	10	13/152 (8.6%)	18	9/153 (5.9%)	11
Metabolism and nutrition disorders
Anorexia	24/150 (16%)	37	36/152 (23.7%)	54	23/153 (15%)	26
Hyperglycaemia	12/150 (8%)	42	10/152 (6.6%)	32	17/153 (11.1%)	46
Hypokalaemia	17/150 (11.3%)	21	12/152 (7.9%)	23	6/153 (3.9%)	6
Hypocalcaemia	10/150 (6.7%)	12	8/152 (5.3%)	18	10/153 (6.5%)	25
Musculoskeletal and connective tissue disorders
Bone pain	46/150 (30.7%)	96	45/152 (29.6%)	77	51/153 (33.3%)	76
Back pain	16/150 (10.7%)	16	17/152 (11.2%)	23	29/153 (19%)	38
Musculoskeletal pain	20/150 (13.3%)	37	18/152 (11.8%)	22	21/153 (13.7%)	38
Arthralgia	11/150 (7.3%)	12	22/152 (14.5%)	28	17/153 (11.1%)	23
Muscle spasms	19/150 (12.7%)	34	17/152 (11.2%)	36	9/153 (5.9%)	9
Pain in extremity	13/150 (8.7%)	18	6/152 (3.9%)	11	10/153 (6.5%)	12
Nervous system disorders
Dizziness	15/150 (10%)	22	20/152 (13.2%)	21	16/153 (10.5%)	21
Paraesthesia	15/150 (10%)	19	10/152 (6.6%)	17	6/153 (3.9%)	7
Headache	11/150 (7.3%)	29	16/152 (10.5%)	26	21/153 (13.7%)	21
Peripheral sensory neuropathy	11/150 (7.3%)	14	9/152 (5.9%)	13	5/153 (3.3%)	10
Dysgeusia	6/150 (4%)	9	10/152 (6.6%)	13	7/153 (4.6%)	7
Psychiatric disorders
Insomnia	17/150 (11.3%)	18	20/152 (13.2%)	23	22/153 (14.4%)	35
Depression	9/150 (6%)	12	17/152 (11.2%)	18	10/153 (6.5%)	10
Respiratory, thoracic and mediastinal disorders
Cough	34/150 (22.7%)	47	27/152 (17.8%)	33	21/153 (13.7%)	29
Dyspnoea	20/150 (13.3%)	34	15/152 (9.9%)	20	18/153 (11.8%)	22
Epistaxis	8/150 (5.3%)	15	7/152 (4.6%)	10	11/153 (7.2%)	16
Pharyngolaryngeal pain	6/150 (4%)	9	9/152 (5.9%)	10	9/153 (5.9%)	11
Skin and subcutaneous tissue disorders
Rash	30/150 (20%)	62	42/152 (27.6%)	63	12/153 (7.8%)	13
Pruritus	16/150 (10.7%)	24	13/152 (8.6%)	16	10/153 (6.5%)	11
Vascular disorders
Hypertension	4/150 (2.7%)	5	9/152 (5.9%)	11	13/153 (8.5%)	23
Hypotension	10/150 (6.7%)	13	4/152 (2.6%)	4	10/153 (6.5%)	10

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

Upon investigator submission of a publication or presentation to Celgene, Celgene shall complete its review within 60 days after receipt of the proposed publication or presentation. Upon Celgene's request, proposed publication or presentation will be delayed up to 90 additional days to enable Celgene to secure adequate intellectual property protection of property of Celgene that would be affected by such proposed publication or presentation.