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

• ClinicalTrials.gov Identifier: NCT00405756
• Recruitment Status: Completed
• First Posted: November 30, 2006
• Results First Posted: May 11, 2012
• Last Update Posted: January 11, 2017
• Sponsor: Celgene Corporation
• Information provided by (Responsible Party): Celgene Corporation

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 (Clinical Trial)
• 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: January 2007
• Actual Primary Completion Date: November 2009
• Actual Study Completion Date: April 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Revlimid
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 Name: 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 Name: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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

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

Criteria

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
4. Karnofsky performance status greater than or equal to 60%.
5. Able to adhere to the study visit schedule and other protocol requirements.

6. Women of Childbearing potential (WCBP) must:

   a. 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.

7. Males Subjects must:

   1. 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.
   2. Agree to not donate semen during study drug therapy and for a period after end of study drug therapy.

8. All subjects must

   1. Have an understanding that the study drug could have potential teratogenic risk.
   2. Agree to abstain from donating blood while taking study drug therapy and following discontinuation of study drug therapy.
   3. Agree not to share study medication with another person.
   4. 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 (1.5*10^9/L) Platelet count < 75,000 cells/uL (75*10^9/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)

7. 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)

8. Neuropathy of >= grade 2 severity.
9. Known human immunodeficiency virus (HIV) positivity or active infectious hepatitis, type A, B or C.

Contacts and Locations

Locations

Australia, Queensland

Hematology Oncology Clinics of Australia, Level 5, Mater Medical Centre

South Brisbane, Queensland, Australia, 4101

Australia, South Australia

Royal Adelaide Hospital Institute of Medical and Veterinary Science

Adelaide, South Australia, Australia, 5000

Australia

Royal Prince Alfred Hospital

Camperdown, Australia, 2050

Peter MacCallum Cancer Centre Divsion of Haematology Medical Oncology

East Melbourne, Australia, 3006

Frankston Hospital

Frankston, Australia, 3199

The Alfred Hospital

Melbourne, Australia, 3141

Sir Charles Gairdner Hospital

Nedlands, Australia, 6009

Princess Alexandra Hospital

Woolloongabba, Australia, 4102

Austria

University Hospital Innsbruck

Innsbruck, Austria, 6020

University Hospital of Salzburg St Johanns Spital

Salzburg, Austria, 5020

Medical University of Vienna

Vienna, Austria, 1090

Wilhelminenspital

Vienna, Austria, 1160

Medical University of Vienna

Vienna, Austria, A-1090

Belarus

Republican Scientific and Practical Centre of Radiation Medicine and Human Ecology

Gomel, Belarus, 246 042

City Clinical Hospital 9

Minsk, Belarus, 220116

Belgium

AZ St-Jan Brugge Oostende AV

Brugge, Belgium, 8000

AZ-VUB

Brussels, Belgium, 1090

UZ Gasthuisberg

Leuven, Belgium, 3000

Centre Hospitalier Universitaire de Liege

Liege, Belgium, 4000

Czech Republic

Fakultni nemocnice Brno

Brno, Czech Republic, 625 00

Fakultni nemocnice Hradec Kralove

Hradec Kralove, Czech Republic, 500 05

Fakultni Nemocnice Olomouc

Olomouc, Czech Republic, 77520

Vseobecna Fakultni Nemocnice v Praze

Prague, Czech Republic, 128 081

Denmark

Hæmatologisk afd. B Aalborg Sygehus Syd

Aalborg, Denmark, 9000

Medicinsk afd. Vejle Sygehus

Vejle, Denmark, 7100

France

CHU

Caen, France, 14033

CH - Hôpital Dupuytren

Limoges Cedex 1, France, 87042

CHU Montpellier- Hopital Lapeyronie

Montpellier Cedex 5, France, 34295

Assistance Publique - Hôpitaux de Paris AP-HP

Paris, France, 75475

CHU Purpan

Toulouse cedex 9, France, TSA 40031-31059

Georgia

Ltd M.Zodelava Hematology Centre

Tbilisi, Georgia, 0112

Institute of Hematology and Transfusiology

Tbilisi, Georgia, 0177

Germany

Medizinische Klinik und Poliklinik II der Charite Campus Mitte

Berlin, Germany, 10117

Universitatsklinikum Carl Gustav Carus an der TU Dresden

Dresden, Germany, D-01307

Universitatsklinikum Freiburg Medizinische Klinik und Poliklinik

Freiburg, Germany, D-79106

Ernst-Moritz-Arndt-Universität Greifswald

Greifswald, Germany, 17487

Universitaetsklinikum Heidelberg Medizinische Klinik und Poliklinik V

Heidelberg, Germany, 69120

Medizinische Klinik und Poliklinik II

Leipzig, Germany, D-04103

Poliklinik A

Münster, Germany, 47589

Medizinische Klinik - Abteilung II

Tübingen, Germany, 72076

Medizinische Universitatsklinik

Ulm, Germany, 89081

Medizinische Klinik und Poliklinik II des Universitatsklinikums Wurzburg

Würzburg, Germany, 97080

Greece

G. GENNIMATAS General Hospital of Athens Department of Hematolgosy

Athens, Greece, 115 27

General Air Force Hospital

Athens, Greece, 11525

Alexandra General Hospital of Athens

Athens, Greece, 11528

Ireland

Hope Directorate Haematology Oncology Service St. James Hospital

Dublin, Ireland, 8

Midlands Regional

Tullamore / Co Offally, Ireland

Israel

Rambam Medical Center

Haifa, Israel, 31096

Hadassah University Hospital

Jerusalem, Israel, 91120

Hematology Institute, Hemato-Oncology Division,Davidoff Cancer Center, Rabin MC Beilinson Hospital

Petch Tikva, Israel, 49100

The Chaim Sheba Medical Center

Tel Hashomer, Israel, 52621

Italy

Policlinico S. Orsola

Bologna, Italy, 40138

A.O.U. San Martino

Genova, Italy, 16132

Dipartmento Oncologico Struttura Complessa di ematlologiaA.O. Ospedale Niguarda Ca Granda

Milano, Italy, 20162

Policlinico San Matteo Universita Di Pavia

Pavia 2, Italy, 27100

Divisione Di Ematologia Ospedale Cattedra di Ematologia

Rome, Italy, 00144

Azienda Policlinico Umberto I, Universita La Sapienzadi Roma

Rome, Italy, 00161

Dipartimento di Onco-Ematologia

San Giovanni Rotondo (FG), Italy, 71013

Azienda Sanitaria Ospedaliera Molinette S. Giovanni Battista

Turin, Italy, 10126

Netherlands

VU Medical Center

Amsterdam, Netherlands, 1081 HV

Erasmus Medical Center

Rotterdam, Netherlands, 3015 GD/3000 CA

Erasmus Medisch Centrum

Rotterdam, Netherlands, 3015 GD

Universitair Medisch Centrum Utrecht

Utrecht, Netherlands

Poland

Klinika Hematologii Samodzielny Publiczny Szpital Kliniczny Akademii

Bialystok, Poland, 15-276

Institute of Internal Diseases University of Medicine

Gdansk, Poland, 80-211

Oddzial Kliniczny Kliniki Hematologii

Krakow, Poland, 31-501

Uniwersytet Medyczny w Lodzi

Lodz, Poland, 93-509

University School of Medicine

Lublin, Poland, 20-290

Akademia Medyczna w Warszawie Samodzielny Publiczny Centralny Szpital Kliniczny

Warsaw, Poland, 02-097

Russian Federation

Burdenko Central Military Clinical Hospital

Moscow, Russian Federation, 105229

Institution of Russian Academy of Medical Sciences Russian Oncological Research Centre n.a. N. N. Bl

Moscow, Russian Federation, 115678

Moscow Regional Research Institute n.a. Vladimirsky

Moscow, Russian Federation, 129110

Novosibirsk State Regional Clinical Hospital

Novosibirsk, Russian Federation, 630087

Medical Radiological Research Center RAMS

Obninsk, Russian Federation, 249036

Samara Regional Clinical Hospital

Samara, Russian Federation, 443095

St. Petersburg Research Institute of Hematology and Blood Transfusion

St. Petersburg, Russian Federation, 191024

Spain

Hospital Clinic

Barcelona, Spain, 08036

Hospital Universitaro Puerta del MarServicio de Hematologia

Cadiz, Spain, 11009

Hospital Universitario de la Princessa

Madrid, Spain, 28006

Hospital Universitario de Salamanca

Salamanca, Spain, 37007

Hospital Virgen del Rocio Servicio de Hematologia

Sevilla, Spain, 41013

Sweden

Medicinkliniken

Boras, Sweden, 501 82

Medicinska kliniken

Malmö, Sweden, 20502

Switzerland

UniversitatsSpital ZurichKlinik fur Onkologie

Zurich, Switzerland, CH-8091

Turkey

Ankara University

Ankara, Turkey, 06620

Marmara School of Medicine

Istanbul, Turkey, 34662

Ege University Medical School

Izmir, Turkey, 35100

Ukraine

Cherkassy Regional Oncology Center

Cherkassy, Ukraine, 18009

Dnepropetrovsk City Clinical Hospital 4

Dnepropetrovsk, Ukraine, 49044

Institute of Urgent and Recovery Surgery

Donetsk, Ukraine, 83047

Institute of Hematology and Transfusiology of the UAMS Department of blood diseases

Kiev, Ukraine, 04060

Institute of Blood Pathology and Transfusion Medicine of the AMS of Ukraine

Lviv 79044, Ukraine

Zhitomir Regional Clinical Hospital

Zhitomir, Ukraine, 10003

United Kingdom

Monklands Hospital

Aidrie, United Kingdom, ML6 0JS

St James's University Hospital

Leeds, United Kingdom, LS7 9TF

University College London Hospitals Cancer Clinical Trials Unitist FloorCentral wing

London, United Kingdom, NW1 2PG

Kings College Hospital

London, United Kingdom, SE5 9RS

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

More Information

Publications of Results:

Dimopoulos MA, Delforge M, Hajek R, Kropff M, Petrucci MT, Lewis P, Nixon A, Zhang J, Mei J, Palumbo A. Lenalidomide, melphalan, and prednisone, followed by lenalidomide maintenance, improves health-related quality of life in newly diagnosed multiple myeloma patients aged 65 years or older: results of a randomized phase III trial. Haematologica. 2013 May;98(5):784-8. doi: 10.3324/haematol.2012.074534. Epub 2012 Dec 14.

Palumbo A, Hajek R, Delforge M, Kropff M, Petrucci MT, Catalano J, Gisslinger H, Wiktor-Jedrzejczak W, Zodelava M, Weisel K, Cascavilla N, Iosava G, Cavo M, Kloczko J, Blade J, Beksac M, Spicka I, Plesner T, Radke J, Langer C, Ben Yehuda D, Corso A, Herbein L, Yu Z, Mei J, Jacques C, Dimopoulos MA; MM-015 Investigators. Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med. 2012 May 10;366(19):1759-69. doi: 10.1056/NEJMoa1112704. Erratum In: N Engl J Med. 2012 Jul 19;367(3):285.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Dimopoulos MA, Petrucci MT, Foa R, Catalano J, Kropff M, Terpos E, Zhang J, Grote L, Jacques C, Palumbo A; MM-015 Investigators. Impact of maintenance therapy on subsequent treatment in patients with newly diagnosed multiple myeloma: use of "progression-free survival 2" as a clinical trial end-point. Haematologica. 2015 Aug;100(8):e328-30. doi: 10.3324/haematol.2014.120790. Epub 2015 Apr 3. No abstract available.

• Responsible Party: Celgene Corporation
• ClinicalTrials.gov Identifier: NCT00405756
• Other Study ID Numbers: CC-5013-MM-015; 2006-001865-41 ( EudraCT Number )
• First Posted: November 30, 2006
• Results First Posted: May 11, 2012
• Last Update Posted: January 11, 2017
• Last Verified: November 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; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Aspirin; Prednisone; Lenalidomide; Melphalan; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents