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
Overview
- Phase
- Phase 3
- Intervention
- Melphalan
- Conditions
- Newly Diagnosed Multiple Myeloma
- Sponsor
- Celgene Corporation
- Enrollment
- 459
- Locations
- 97
- Primary Endpoint
- Kaplan Meier Estimates of Progression-free Survival (PFS) Based on the Response Assessment by the Central Adjudication Committee (CAC)
- Status
- Completed
- Last Updated
- 9 years ago
Overview
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.
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
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.
Intervention: Melphalan
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.
Intervention: Prednisone
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.
Intervention: Aspirin
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.
Intervention: Melphalan
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.
Intervention: Prednisone
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.
Intervention: Aspirin
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.
Intervention: Placebo
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.
Intervention: Melphalan
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.
Intervention: Prednisone
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.
Intervention: Aspirin
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.
Intervention: Placebo
Outcomes
Primary Outcomes
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 Outcomes
- Kaplan Meier Estimates of Progression-free Survival (PFS) From Start of Maintenance Therapy Period Based on the Response Assessment by the Central Adjudication Committee (CAC)(Approximately week 37 (start of cycle 10) to week 165)
- Kaplan Meier Estimates of Overall Survival (OS)(up to 177 weeks)
- Kaplan Meier Estimates of Time to Progression (TTP) Based on the Response Assessment by the Central Adjudication Committee (CAC)(up to 165 weeks)
- Number of Participants in Disease Response Categories Representing Their Best Response During the Double-blind Treatment Period(Up to 165 weeks)
- Time to First Response(Up to 66 weeks)
- Kaplan Meier Estimates for Duration of Response as Determined by the Central Adjudication Committee (CAC)(Up to 149 weeks)
- Kaplan Meier Estimates for Time to Next Antimyeloma Therapy(Up to 168 weeks)
- Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period(Up to 169 weeks (Double-blind therapy period plus 4 weeks))
- Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Quality of Life Scale(Baseline (Day 0), Months 4, 7, 10, 13, 16)
- Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Physical Functioning Scale(Baseline (Day 0), Months 4, 7, 10, 13, 16)
- Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Role Functioning Scale(Baseline (Day 0), Months 4, 7, 10, 13, 16)
- Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Emotional Functioning Scale(Baseline (Day 0), Months 4, 7, 10, 13, 16)
- Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Congitive Functioning Scale(Baseline (Day 0), Months 4, 7, 10, 13, 16)
- Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Social Functioning Scale(Baseline (Day 0), Months 4, 7, 10, 13, 16)
- Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Scale(Baseline (Day 0), Months 4, 7, 10, 13, 16)
- Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Nausea and Vomiting Scale(Baseline (Day 0), Months 4, 7, 10, 13, 16)
- Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Pain Scale(Baseline (Day 0), Months 4, 7, 10, 13, 16)
- Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Diarrhoea Scale(Baseline (Day 0), Months 4, 7, 10, 13, 16)
- Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Dyspnoea Scale(Baseline (Day 0), Months 4, 7, 10, 13, 16)
- Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Insomnia Scale(Baseline (Day 0), Months 4, 7, 10, 13, 16)
- Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Appetite Loss Scale(Baseline (Day 0), Months 4, 7, 10, 13, 16)
- Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Constipation Scale(Baseline (Day 0), Months 4, 7, 10, 13, 16)
- Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Financial Difficulties Scale(Baseline (Day 0), Months 4, 7, 10, 13, 16)
- Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms Scale(Baseline (Day 0), Months 4, 7, 10, 13, 16)
- Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Side Effects of Treatment Scale(Baseline (Day 0), Months 4, 7, 10, 13, 16)
- Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Future Perspective Scale(Baseline (Day 0), Months 4, 7, 10, 13, 16)
- Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Body Image Scale(Baseline (Day 0), Months 4, 7, 10, 13, 16)