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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT00405756
First received: November 29, 2006
Last updated: August 20, 2014
Last verified: August 2014
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III, Multicentre, Randomised, Double-Blind, Placebo-Controlled, 3 Arm Parallel-Group Study to Determine the Efficacy and Safety of Lenalidomide (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

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

    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:
  • 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 ] [ Designated as safety issue: No ]

    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.


  • Kaplan Meier Estimates of Overall Survival (OS) [ Time Frame: up to 177 weeks ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]

    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.


  • Number of Participants in Disease Response Categories Representing Their Best Response During the Double-blind Treatment Period [ Time Frame: Up to 165 weeks ] [ Designated as safety issue: No ]
    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 to First Response [ Time Frame: Up to 66 weeks ] [ Designated as safety issue: No ]
    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.

  • Kaplan Meier Estimates for Duration of Response as Determined by the Central Adjudication Committee (CAC) [ Time Frame: Up to 149 weeks ] [ Designated as safety issue: No ]

    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.


  • Kaplan Meier Estimates for Time to Next Antimyeloma Therapy [ Time Frame: Up to 168 weeks ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: Yes ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 459
Study Start Date: February 2007
Estimated Study Completion Date: September 2014
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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 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 MPp 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.

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00405756

  Hide Study Locations
Locations
Australia, New South Wales
Royal Prince Alfred Hopstial
Camperdown, New South Wales, Australia, 2050
Australia, Queensland
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia, 4102
Australia, South Australia
Institute of Medical and Veterinary Science, Division of Haematology
Adelaide, South Australia, Australia, 5000
Australia, Victoria
Peter MacCallum Cancer Department of Haematology
East Melbourne, Victoria, Australia, 3002
Peninsula & South East Haematology & Oncology Group
Frankston, Victoria, Australia, 3199
The Alfred Hospital
Melbourne, Victoria, Australia, 3007
Australia
Haematology Care Centre, Sir Charles Gairdner Hospital
Nedlands, Australia, WA 6009
Mater Medical Center
South Brisbane, Australia, QLD 4101
Austria
Medizinische Universitätsklinik Innsbruck, Universitätsklinik für Innere Medizin, Klinische Abt. für Hämatologe und Onkologie
Innsbruck, Austria, 6020
Salzburger Landkliniken, St Johanns-Spital, Universitatsklink fur Innere Medizin III
Salzburg, Austria, A -5020
Medizinische Universitat Wien, Innere Medizin I, Klinische Abteilung fur Onkologie
Vienna, Austria, A-1090
Center for Oncology and Hematology, Department of Medicine
Vienna, Austria
Medizinische Abteilung Zentrum für Onkologie und Hämatologie
Wien, Austria, 1171
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 Sint Jan, Dienst Hematologie
Brugge, Belgium
AZ-VUB Brussels
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
Fakultní nemocnice Olomouc
Olomouc, Czech Republic, 775 20
Vseobecna fakultni nemocnice v Praze
Prague, Czech Republic, 128 08
Denmark
Hæmatologisk afd. B Aalborg Sygehus Syd
Aalborg, Denmark, 9000
Medicinsk afd. Vejle Sygehus
Vejle, Denmark, 7100
France
C.H.U Caen
Caen, France, 14000
Service Hématologie Clinique et Thérapies Cellulaires
Limoges, France
Recherche Clinique Hematologie et Oncologie Medicale CHU Lapeyronie
Montpellier Cedex, France, 34295
Assistance Hopitaux Publique De Paris
Paris, France, 75475
CHU Purpan
Toulouse Cedex 9, France, TSA 40031-31059
Georgia
Clinic of Hematology and Chemotherapy
Tblisis, Georgia, 0179
Institute of Hematology and Transfusiology
Tblisis, Georgia, 0177
Germany
Charité - Universitätsmedizin Berlin Centrum Tumormedizin
Berlin, Germany, 10117
Universitätsklinikum Carl Gustav Carus an der TU Dresden, Medizinische Klinik und Poliklinik I
Dresden, Germany, D-01307
Universitätsklinikum Freiburg, Medizinische Klinik und Poliklinik, Abteilung Innere Medizin I, Hämotologie/Onkologie
Freiburg, Germany, D-79106
Hämatologie, Onkologie und Transplantationszentrum Klinik und Poliklinik für Innere Medizin C, Ernst Moritz-Arndt-Universität Greifswald
Greifswald, Germany, 17487
Universität Heidelberg, Medizinische Klinik und Poliklinik V
Heidelberg, Germany, 69120
Universitätsklinikum Leipzig, Zentrum für Innere Medizin, Medizinische Klinik und Poliklinik II
Leipzig, Germany, D-04103
Universitatsklinikum Muenster Medizinische Klinik und Poliklinik A
Muenster, Germany, 48149
Medizinische Universitätsklinik Hämatologie, Onkologie, Immunologie und Pulmologie
Tübingen, Germany, 72076
Universitätsklinikum Ulm
Ulm, Germany
Medizinische Klinik und Poliklinik II des Universitätsklinikums Würzburg
Würzburg, Germany, 97080
Greece
"Alexandra" General Hospital of Athens
Athens, Greece, 11528
"251" General Air Force Hospital
Athens, Greece, GR-11525
Genimata Hospital
Athens, Greece, 115 27
"Theagenio" Anticancer Hospital of Thessaloniki
Thessaloniki, Greece, 540 07
Ireland
Midland Regional Hospital
Tullamore Co., Offaly, Ireland
St.James' Hospital
Dublin 8, Ireland
Israel
Rambam Health Care Campus
Haifa, Israel, 31096
Hadassah Medical Organization
Jerusalem, Israel, 91120
Davidoff Cancer Center Rabin Medical Center, Beilinson Hospital
Petah Tikva, Israel, 49100
The Chaim Sheba Medical Center
Tel Hashomer, Israel, 52621
Italy
Istituto di Ematologia ed Oncologia Medica
Bologna, Italy, 40137
Azienda ospedaliera universitaria S.Martino, Clinica Ematologica
Genova, Italy, 16132
Ospedale Niguarda Ca Granda
Milano, Italy, 20162
Divisione di Ematologia
Pavia, Italy, 27100
Divisione Di Ematologia, Ospedale
Rome, Italy, 00144
Divisione di Ematologia ed Immunoematologia
Rome, Italy, 00161
Dipartimento di Onco-Ematologia
San Giovanni Rotondo (FG), Italy
Divisione Universitaria di Ematologia
Torino, Italy, 101 26
Netherlands
VU University Medical Center
Amsterdam, Netherlands, 1081 HV
Erasmus MC
Rotterdam, Netherlands, 3015 GD
Universitair Medisch Centrum Utrecht
Utrecht, Netherlands, 3584 CX
Poland
Klinika Hematologii Samodzielny Publiczny Szpital Kliniczny Akademii
Bialystok, Poland, 15-276
Klinika Hematologii Akademii Medycznej w. Gdanska
Gdansk, Poland, 80-211
Oddzial Kliniczny Kliniki Hematologii
Krakow, Poland, 31-501
Uniwersytet Medyczny w Lodzi
Lodz, Poland, 93-509
Lublinie Klinika Hematoonkologii i Transplantacji Szpiku
Lublin, Poland, 20-081
Akademia Medyczna w Warszawie Samodzielny Publiczny Centralny Szpital Kliniczny
Warsaw, Poland, 02-097
Russian Federation
GU Russian Oncological Research Center
Moscow, Russian Federation, 115478
Moscow Regional Research Institute n.a. Vladimirsky
Moscow, Russian Federation, 129110
Burdenko Main Military Clinical Hospital
Moscow, Russian Federation, 105229
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
Russian Research Institute of Hematology and Blood Transfusiology
St. Petersburg, Russian Federation, 191024
Spain
Hospital Clinico Servico Hematologia
Barcelona, Spain, 08036
Servicio de Hematología
Cadiz, Spain
Hospital General de Jerez de la Frontera Laboratorio de Hematología
Jerez de la Frontera- Cádiz, Spain, 11407
Hospital Universitario de la Princesa
Madrid, Spain, 28006
Hospital Universitario
Salamanca, Spain, 37 007
Hospital Virgen del Rocio
Sevilla, Spain, 41013
Sweden
Department of Hematology, Sahlgrenska University Hospital
Göteborg, Sweden, 413 45
Department of Hematology, MAS University Hospital
Malmö, Sweden, 205 02
Switzerland
Universitätsspital ZürichKlinik für Onkologie
Zurich, Switzerland, CH-8091
Turkey
Ege University Medical Faculty
Izmir, Bornova, Turkey, 35100
Ankara University Medical Faculty
Ankara, Dikimevi, Turkey, 06620
Marmara University Medical Faculty
Istanbul, Turkey
Ukraine
Cherkassy Oblsat Oncology Dispensary
Cherkassy, Ukraine, 18009
Oblast Hematology Centre
Dnepropetrovsk, Ukraine, 49044
City Multifield Clinical Hospital #4
Dnipropetrovsk, Ukraine, 49102
Institute of Urgent and Recovery Surgery, Department of Hospital Therapy
Donetsk, Ukraine
Institute of Hematology and Transfusiology of AMS of Ukraine
Kyiv, Ukraine, 04112
Institute of Blood Pathology and Transfusion Medicine of the AMS of Ukraine
Lviv, Ukraine
Zhitomir Regional Clinical Hospital
Zhitomir, Ukraine, 10003
United Kingdom
Monklands Hospital
Aidrie, United Kingdom, ML6 0JS
Kings College Hospital
London, United Kingdom, SE5 9RS
Cancer Clinical Trials Unit (Haematology)
London, United Kingdom, NW1 2PG
Sponsors and Collaborators
Celgene Corporation
Investigators
Principal Investigator: Antonio Palumbo, M.D. Azienda Sanitaria Ospedaliera Molinette S. Giovanni Battista
  More Information

No publications provided by Celgene Corporation

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT00405756     History of Changes
Other Study ID Numbers: CC-5013-MM-015, 2006-001865-41
Study First Received: November 29, 2006
Results First Received: April 16, 2012
Last Updated: August 20, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Agency for Health and Food Safety
Belarus: Ministry of Health
Belgium: Federal Agency for Medicinal Products and Health Products
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Georgia: Ministry of Health
Greece: National Organization of Medicines
Ireland: Irish Medicines Board
Israel: Israeli Health Ministry Pharmaceutical Administration
Italy: The Italian Medicines Agency
Netherlands: Dutch Health Care Inspectorate
Poland: The Central Register of Clinical Trials
Russia: Ministry of Health of the Russian Federation
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Switzerland: Swissmedic
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Ukraine: Ministry of Health

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
Melphalan
Lenalidomide
Thalidomide
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents

ClinicalTrials.gov processed this record on August 27, 2014