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
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.
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
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
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.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Kaplan Meier Estimates of Progression-free Survival (PFS) Based on the Response Assessment by the Central Adjudication Committee (CAC)
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.
up to 165 weeks
Antonio Palumbo, M.D.
Azienda Sanitaria Ospedaliera Molinette S. Giovanni Battista
Australia: Department of Health and Ageing Therapeutic Goods Administration