Clinical trial NCT00405756
Conditions: Newly Diagnosed Multiple Myeloma
Keywords: Newly Diagnosed Multiple Myeloma Celgene CC-5013 Revlimid Lenalidomide Melphalan Prednisone Elderly
Sponsor: Celgene Corporation
Start date: 2007-01-01; Completion date: 2016-04-01
Enrollment: 459 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: 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. arm 2: 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. arm 3: 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.
Interventions: intervention 1: Lenalidomide: Double-blind Induction intervention 2: Melphalan intervention 3: Prednisone intervention 4: Aspirin intervention 5: Placebo intervention 6: Lenalidomide: Double-blind Maintenance intervention 7: Lenalidomide: Open-label
Intervention descriptions: intervention 1: 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. intervention 2: 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. intervention 3: 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. intervention 4: Double-blind induction: low-dose aspirin 75 mg to 100 mg daily for all treatment arms.

Double-blind maintenance: at the investigator's discretion intervention 5: 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. intervention 6: Single-agent oral lenalidomide 10 mg once daily on Days 1 through 21 of each 28-day cycle from cycle 10 to disease progression. intervention 7: 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.

Protocol documents: