The MM5 trial: evaluation of two regimens of bortezomib-based induction therapy and of lenalidomide consolidation followed by lenalidomide maintenance treatment in patients with multiple myeloma

INTERVENTION: Patients are randomised into four treatment arms (A1, A2, B1, B2). Patients included in arms A1/B1 are treated with 3 cycles PAd (bortezomib 1.3 mg/m^2 intravenous [iv] on days 1, 4, 8 and 11, doxorubicin 9 mg/m^2 iv on days 1 ‐ 4, dexamethasone [Dex] orally [po] 20 mg/d on days 1 ‐ 4, 9 ‐ 12 and 17 ‐ 20). Patients in arm A2/B2 are treated with 3 cycles VCD (bortezomib 1.3 mg/m^2 iv on days 1, 4, 8 and 11, cyclophosphamide 900 mg/m^2 iv on day 1, dexamethasone po 40 mg/d on days 1 ‐ 2, 4 ‐ 5, 8 ‐ 9, 11 ‐ 12). Standard intensification treatment will be done according to local protocols. Thereafter, two cycles of lenalidomide 25 mg/d on days 1 ‐ 21 are given, followed by a lenalidomide maintenance treatment (lenalidomide orally [po] 10 mg/d in the first three months, thereafter 15 mg/d). In arms A1 and A2 lenalidomide maintenance will be given for a period of 2 years, in arms B1 and B2 until a CR is reached. CONDITION: Multiple myeloma ; Cancer ; Multiple myeloma and malignant plasma cell neoplasms PRIMARY OUTCOME: 1. Response to treatment (very good partial remission or better) after induction therapy, measured after induction therapy; 2. Progression‐free survival (i.e., time from randomisation to progression or death from any; cause whichever occurs first), measured at several timepoints during study and follow up if there is a progression of the disease SECONDARY OUTCOME: 1. Overall survival defined as time from randomisation to death from any cause. Patients still alive or lost to follow up are censored at the date they were last known to be alive.; 2. Response rates (response rates will be assessed using the following subcategories: SD, MR, PR, VGPR [with subgroup nCR], CR, sCR, mCR). Response measured after induction, after intensification, after consolidation and during maintenance.; 3. Toxicity ([serious] adverse events CTC grade 3 and grade 4, CTC‐AE v4.0), measured at induction, consolidation and maintenance treatment INCLUSION CRITERIA: 1. Confirmed diagnosis of multiple myeloma requiring systemic therapy 2. Measurable disease 3. Aged 18 ‐ 70 years inclusive, either sex