A Randomized Phase II Dose Finding Study of Revlimid™ and Melphalan in Patients With Previously Untreated Multiple Myeloma
- Evaluate the tolerability of 2 different doses of lenalidomide when administered with
melphalan in patients with previously untreated multiple myeloma who are not planning
to undergo future autologous stem cell transplantation.
- Characterize the toxicity profile of lenalidomide in combination with melphalan.
- Determine tumor response in these patients after 2 and 12 courses of induction therapy
with lenalidomide and melphalan and after 6 months of maintenance therapy with
- Determine progression-free and overall survival of these patients.
- Determine time to dose modification and time to dose discontinuation in these patients.
- Examine wnt pathway inhibition in response to lenalidomide on pre- and post-treatment
bone marrow and blood samples using enzyme-linked immunosorbent assay (ELISA), gene
expression profiling, drosophila-based chemical genetics, and surface-enhanced laser
desorption/ionization mass spectrometry (SELDI MS) proteomics.
OUTLINE: This is a multicenter, randomized, open-label, dose-finding study of lenalidomide.
Prior to randomization, 6 patients receive oral lenalidomide at a lower dose (same dose to
be used in arm I) once daily on days 1-21 and oral melphalan once daily on days 1-4.
Treatment repeats every 28 days for 3 courses. If no unacceptable toxicity occurs, the trial
will proceed and randomization will occur.
- Induction therapy: Patients are randomized to 1 of 2 dose levels of lenalidomide.
- Arm I: Patients receive oral lenalidomide once daily on days 1-21 and oral
melphalan once daily on days 1-4.
- Arm II: Patients receive oral lenalidomide as in arm I, but at a lower dose, and
melphalan as in arm I, but at a higher dose.
Treatment in both arms repeats every 28 days for up to 12 courses in the absence of disease
progression or unacceptable toxicity. After 12 courses of induction therapy, patients in
both arms without progressive disease proceed to maintenance therapy.
- Maintenance therapy: Patients receive oral dexamethasone once daily on days 1-4.
Courses repeat every 28 days in the absence of disease progression or unacceptable
After completion of study treatment, patients are followed at 4 weeks and then every 2
PROJECTED ACCRUAL: A total of 92 patients will be accrued for this study.
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Incidence of dose-limiting toxicity within first 3 courses of treatment
Darrell White, MD
Nova Scotia Cancer Centre
United States: Federal Government