Phase II study of Bortezomib, Melphalan, Prednisone (VMP) followed by Lenalidomide maintenance vs. VMP without maintenance in Myeloma patients not eligible to high-dose chemotherapy and autologous stem cell transplantation – a GERman MAINtenance study (GERMAIN)(GERMAIN)

INTERVENTION: Trade Name: Revlimid Pharmaceutical Form: Capsule, hard INN or Proposed INN: LENALIDOMIDE CAS Number: 191732‐72‐6 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 5‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use CONDITION: multiple myeloma ; MedDRA version: 19.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864 Therapeutic area: Diseases [C] ‐ Blood and lymphatic diseases [C15] PRIMARY OUTCOME: Main Objective: To estimate the gain in Progression Free Survival (PFS) by maintenance with lenalidomide after induction with VMP in elderly or unfit for high‐dose chemotherapy patients. Primary end point(s): Median Progression free survival Secondary Objective: 1. To compare the safety of VMP and Lenalidomide maintenance versus VMP and placebo. ; 2. To compare the QoL of VMP and Lenalidomide maintenance versus VMP and placebo.; 3. To assess the safety and efficacy of Rd for poor responders on VMP. Timepoint(s) of evaluation of this end point: time from randomization to the first documentation of disease progression based on the IMWG criteria, or death due to any cause during the study up to the end of the PFS follow‐up phase SECONDARY OUTCOME: Secondary end point(s): 1. Overall survival to 5 years ; 2. sequence progression free survival ; 3. sequence overall survival to 5 years ; 4. Time to treatment failure ; 5. Other efficacy parameters according to the international uniform response criteria, including objective response (complete response [CR], stringent complete response [sCR], very good partial response (VGPR), partial response [PR], and overall response [CR + VGPR + PR] using IMWG criteria) ; 6. Safety (adverse events [type, frequency, and severity of AEs, and relationship of AEs to study drug], laboratory abnormalities, and hospitalizations) including frequency of Second Primary Malignancies (SPM reporting during the whole study including open label follow‐up phase for all patients) ; 7. Quality of life (QOL); European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ‐C30) and QLQ for Patients with Multiple Myeloma (QLQ‐MY20) Module and the descriptive system of the EQ‐5D ; 8. Safety and response rate on Rd for poor responders on VMP ; Timepoint(s) of evaluation of this end point: 1. end of trial ; 2. end of trial ; 3. end of trial ; 4. end of trial ; 5. end of trial ; 6. end of trial ; 7. at start of maintenance therapy, then every 6 months until end of maintenance ; 8. end of trial INCLUSION CRITERIA: 1. Must understand and voluntarily sign an informed consent form. 2. Must be =18 years of age at the time of signing the informed consent form. 3. Must be able to adhere to the study visit schedule and other protocol requirements. 4. Previously untreated, symptomatic multiple myeloma as defined by the 3 criteria below: • MM diagnostic criteria (all 3 required): ‐ Monoclonal plasma cells in the bone marrow =10% and/or presence of a biopsy‐proven plasmacytoma ‐ Monoclonal protein present in the serum and/or urine ‐ Myeloma‐related organ dysfunction (at least one of the following): [C] Calcium elevation in the blood (serum calcium >10.5 mg/dl or upper limit of normal) [R] Renal insufficiency (serum creatinine >2 mg/dl) [A] Anemia (hemoglobin <10 g/dl or 2 g < laboratory normal) [B] Lytic bone lesions or osteoporosis AND have measurable disease by protein electrophoresis analyses as defined by the following: •