Lenalidomide Plus Melphalan as a Preparative Regimen for Autologous Stem Cell Transplantation in Relapsed Multiple Myeloma: A Phase 1 / 2 Study
brief summary
A) Phase 1: To determine the maximal tolerated dose (MTD) of lenalidomide that can be safely added to high-dose melphalan prior to autologous stem cell transplantation (ASCT). B) Phase 2: To determine whether the addition of high-dose lenalidomide to ASCT followed by maintenance standard-dose lenalidomide improves the response rate and duration of response for relapsed multiple myeloma (RMM).
detailed description
Experimental: Phase 1 Subjects will dose escalate lenalidomide in a series of subjects in a 3+3 design through 6 dose levels of lenalidomide (as per modified Fibonacci escalation) to determine the maximal tolerated dose (MTD)of lenalidomide prior to ASCT.
Planned dose levels of lenalidomide in Phase 1 portion of study:
Dose Level/ Lenalidomide Dose / Schedule
-1: 25mg daily x 5 days
1. 25mg twice daily x 5 days 2. 25mg qAM, 50mq qPM x 5 days 3. 50mg qAM, 75mg qPM x 5 days 4. 75mg qAM, 100mg qPM x 5 days 5. 100mg qAM, 150mg qPM x 5 days 6. 150mg qAM, 200mg qPM x 5 days
Experimental: Phase 2 The MTD determine for lenalidomide in the phase 1 portion of this study will be used in the transplant phase of the phase 2 portion.
In the transplant phase of the study, all participants will receive oral lenalidomide at the pre-determined dose level for phase 1 and MTD for phase 2 for 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells.
Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles).