Stem Cell Transplant With Lenalidomide Maintenance in Patients With Multiple Myeloma (BMT CTN 0702)
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Lenalidomide; lenalidomide, bortezomib and dexamethasone; Lenalidomide
Intervention description: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive a second autologous PBSC transplant with the same conditioning regimen as the first transplant. All patients will also receive maintenance lenalidomide which will start after the second transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.; All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive consolidation therapy with RVD (lenalidomide 15 mg/day on Days 1-14, dexamethasone 40mg on Days 1, 8 and 15, and bortezomib 1.3mg/m2 on Days 1, 4, 8 and 11 of every 21 day cycle, patients will receive four cycles). All patients will also receive maintenance lenalidomide which will start after consolidation therapy. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.; All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive maintenance with lenalidomide (15 mg daily). Maintenance lenalidomide will start after the first autologous transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.
Intervention MeSH terms: Dexamethasone; Lenalidomide; Bortezomib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 758.0
Sex: All
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Symptomatic Multiple Myeloma; Lenalidomide; Anti-Myeloma Agents; Hematologic Disorders; Maintenance Therapy; Progression; Autologous Transplant; RVD Consolidation

Summary:

      The study is designed as a Phase III, multicenter trial of tandem autologous transplants plus
      maintenance therapy versus the strategy of single autologous transplant plus consolidation
      therapy with lenalidomide, bortezomib and dexamethasone (RVD) followed by maintenance therapy
      or single autologous transplant plus maintenance therapy as part of upfront treatment of
      multiple myeloma (MM). Lenalidomide will be used as maintenance therapy for three years in
      all arms.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients meeting the criteria for symptomatic multiple myeloma (MM).

          -  Patients who are 70 years of age, or younger, at time of enrollment.

          -  Patients who have received at least two cycles of any regimen as initial systemic
             therapy and are within 2 - 12 months of the first dose of initial therapy.

          -  Cardiac function: left ventricular ejection fraction at rest greater than 40 percent.

          -  Hepatic: bilirubin less than 1.5x the upper limit of normal and alanine
             aminotransferase (ALT) and aspartate aminotransferase (AST) less than 2.5x the upper
             limit of normal. (Patients who have been diagnosed with Gilbert's Disease are allowed
             to exceed the defined bilirubin value of 1.5x the upper limit of normal.)

          -  Renal: Creatinine clearance of grater than or equal to 40 mL/min, estimated or
             calculated.

          -  Pulmonary: Diffusing capacity of the lung for carbon monoxide (DLCO), forced
             expiratory volume in one second (FEV1), or forced vital capacity (FVC) greater than 50
             percent of predicted value (corrected for hemoglobin).

          -  Patients with an adequate autologous graft defined as a cryopreserved PBSC graft
             containing greater than or equal to 4 x 10^6 CD34+ cells/kg patient weight. The graft
             may not be CD34+ selected or otherwise manipulated to remove tumor or other cells. The
             graft can be collected at the transplanting institution or by a referring center. The
             autograft must be stored so that there are two products each containing at least 2 x
             10^6 CD34+ cells/kg patient weight.

          -  Signed informed consent form.

        Exclusion Criteria:

          -  Patients who never fulfill the criteria for symptomatic MM.

          -  Patients with purely non-secretory MM [absence of a monoclonal protein (M protein) in
             serum as measured by electrophoresis and immunofixation and the absence of Bence Jones
             protein in the urine defined by use of conventional electrophoresis and immunofixation
             techniques]. Patients with light chain MM detected in the serum by free light chain
             assay are eligible.

          -  Patients with plasma cell leukemia.

          -  Karnofsky performance score less than 70 percent.

          -  Patients with greater than grade 2 sensory neuropathy (CTCAE).

          -  Patients with uncontrolled bacterial, viral or fungal infections (currently taking
             medication and progression of clinical symptoms).

          -  Patients seropositive for the human immunodeficiency virus (HIV).

          -  Myocardial infarction within 6 months prior to enrollment or has New York Heart
             Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe
             uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
             ischemia or active conduction system abnormalities. Prior to study entry, any ECG
             abnormality at Screening has to be documented by the investigator as not medically
             relevant.

          -  Patient has hypersensitivity to bortezomib, boron or mannitol.

          -  Patient has received other investigational drugs with 14 days before enrollment.

          -  Patients with prior malignancies except resected basal cell carcinoma or treated
             cervical carcinoma in situ. Cancer treated with curative intent less than 5 years
             previously will not be allowed unless approved by the Protocol Officer or one of the
             Protocol Chairs. Cancer treated with curative intent greater than 5 years previously
             is allowed.

          -  Female patients who are pregnant (positive B-HCG) or breastfeeding.

          -  Females of childbearing potential (FCBP) or men who have sexual contact with FCBP
             unwilling to use contraceptive techniques during the length of lenalidomide
             maintenance therapy.

          -  Prior allograft or prior autograft.

          -  Patients who have received mid-intensity melphalan (greater than 50 mg IV) as part of
             prior therapy.

          -  Patients unable or unwilling to provide informed consent.

          -  Prior organ transplant requiring immunosuppressive therapy.

          -  Patients with disease progression prior to enrollment.

          -  Patients who have received lenalidomide as initial therapy for MM and have experienced
             toxicities resulting in treatment discontinuation.

          -  Patients who experienced thromboembolic events while on full anticoagulation during
             prior therapy with lenalidomide or thalidomide.

          -  Patients unwilling to take deep vein thrombosis (DVT) prophylaxis.

          -  Patients who cannot undergo an intervention in any treatment arm due to a priori
             denial of medical costs coverage by third party payers.

          -  Patients unable to unwilling to return to the transplant center for their assigned
             treatments.