Bendamustine, thalidomide, dexamethasone dose escalation study in relapsed/refractory myeloma

INTERVENTION: Arm A: Bendamustine (60), thalidomide, dexamethasone ‐ Bendamustine: Intravenous at 60 mg/m2/day on days 1 and 2 (30 ‐ 60 minute infusion each day) Thalidomide: Oral at 100 mg/day on days 1 ‐ 28 Dexamethasone: Oral at 20 mg/day on days 1 ‐ 4 and 15 ‐ 18 Arm B: Bendamustine (100), thalidomide, dexamethasone ‐ Bendamustine: Intravenous at 100 mg/m2/day on days 1 and 2 (30 ‐ 60 minute infusion each day) Thalidomide: Oral at 100 mg/day on days 1 ‐ 28 Dexamethasone: Oral at 20 mg/day on days 1 ‐ 4 and 15 ‐ 18 Each cycle is repeated at 28 days. Patients continue treatment until maximum response plus 2 cycles. Assuming tolerability, a minimum of 6 and maximum of 9 cycles will be given. Patients will be followed up every 12 weeks for one year after the entry of the last patient (i.e. minimum of 1 year, maximum 2 years). CONDITION: Multiple myeloma ; Cancer ; Multiple myeloma PRIMARY OUTCOME: 1. Proportion of patients achieving at least a partial response (as defined by the Modified International Working Group [IWG] Uniform Response Criteria) within six cycles of treatment, measured within 6 months of start of treatment, i.e., 18 months post‐first patient; 2. Proportion of patients successfully able to receive their second cycle of bendamustine within six weeks of receiving their first cycle, measured within 6 months of start of treatment, i.e., 18 months post‐first patient; 3. Progression‐free survival, measured at 12 months post‐randomisation, i.e., 24 months post first patient SECONDARY OUTCOME: 1. Maximum response rate; 2. Overall response rate ; 3. Response duration; 4. Time to next treatment; 5. Proportion of patients successfully receiving six cycles of treatment with no dose reductions or delays; 6. Safety and toxicity; 7. Feasibility of stem cell harvest following treatment (in eligible refractory patients); ; All measured within 12 months of randomisation, i.e., within 24 months post‐first patient INCLUSION CRITERIA: Current inclusion criteria as of 13/08/2012: 1. Aged greater than or equal to 18 years, either sex 2. Histologically confirmed multiple myeloma (MM) with measurable disease parameters requiring therapy for relapsed or refractory disease 3. Unsupported platelet count >75 x 109/L within 48 hours before registration 4. Absolute neutrophil count >1.5 x 109/L within 48 hours before registration. GCSF is permitted for no more than 7 days prior to registration. 5. Able to provide written informed consent 6. Performance status (Eastern Cooperative Oncology Group [ECOG]) 0 ‐ 3 7. Life expectancy at least 3 months Previous inclusion criteria until 13/08/2012: 1. Aged greater than or equal to 18 years, either sex 2. Histologically confirmed multiple myeloma (MM) with measurable disease parameters requiring therapy for relapsed or refractory disease 3. Able to provide written informed consent 4. Performance status (Eastern Cooperativ