Stem Cell Transplantation in Individuals With Multiple Myeloma (BMT CTN 0102)
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: One Autologous Transplant; Non-Myeloablative Allogeneic Transplant; Second Autologous Transplant; Thalidomide; Dexamethasone; Observation
Intervention description: Melphalan will be administered at a dose of 200 mg/m2. Melphalan will be given in one dose infused on Day -2. Melphalan dose is based on ideal body weight (IBW) for patients who weigh 100-120% of their IBW. All patients will receive an autologous graft with a minimum cell dose of 2.0 x 106 CD34+ cells/kg patient weight. Patients will receive ~5 ug/kg/day of Granulocyte-Colony Stimulating Factor (G-CSF) subcutaneously from Day 5 post-transplant until absolute neutrophil count (ANC) > 500/mm3 for two days.; Upon recovery and at least Day 60 post-autograft, patients with an available 6/6 HLA matched sibling will receive an allograft after non-myeloablative conditioning. Day 0 patients will receive Total Body Irradiation (TBI) 2.0 Gy from a linear accelerator ≤ 20 cGy/min, followed by allogeneic peripheral blood stem cell (PBSC) infusion. Commence cyclosporine (CSA) on Day -3 at 5 mg/kg bid PO for a daily dose of 10 mg/kg/day through Day +84 based on actual body weight. Starting on Day 84, patients in partial or complete response with the absence of graph versus host disease (GVHD) will have CSA tapered so the patient will be off CSA by Day 180. Oral administration of Mycophenolate Mofetil will be at a daily dose of 30 mg/kg/day from the evening of Day 0 until Day 27 post-transplant.; Upon recovery from the first autograft, but at least 60 days (preferably between 60-120 days) after the first autograft, patients without an HLA-matched sibling donor will receive a second autograft, also conditioned with melphalan 200 mg/m2.; Patients will be initiated on a starting dose of 50 mg/day. The dose will be increased weekly by 50 mg as tolerated to achieve a target dose of 200 mg/day. Patients will be treated for 12 months with thalidomide.; Patients will receive dexamethasone at a dose of 40 mg per day during Days 1-4 of each month for 12 months. The first dose of dexamethasone to be given the same day the patient starts thalidomide.; One year of observation post-transplants.
Intervention MeSH terms: Thalidomide; Dexamethasone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 710.0
Sex: All
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Stage II Multiple Myeloma; Stage III Multiple Myeloma; Refractory Plasma Cell Neoplasm

Summary:

      The study is designed as a Phase III, multi-center trial of tandem autologous transplants
      versus the strategy of autologous followed by Human Leukocyte Antigen (HLA)-matched sibling
      non-myeloablative allogeneic transplant. Study subjects will be biologically assigned to the
      appropriate arm depending on the availability of an HLA-matched sibling. There is a nested
      randomized phase III trial of observation versus maintenance therapy following the second
      autologous transplant for patients on the tandem autologous transplant arm.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Meeting the Durie and Salmon criteria for initial diagnosis of MM

          -  Stage II or III MM at diagnosis or anytime thereafter

          -  Symptomatic MM requiring treatment at diagnosis or anytime thereafter

          -  Received at least three cycles of initial systemic therapy and are within 2-10 months
             of initiation of the initial therapy (this time frame excludes the time for
             mobilization therapy)

          -  If receiving chemotherapy-based mobilization regimens, must be able to receive
             high-dose melphalan between 2 and 8 weeks after the initiation of mobilization therapy
             whether delivered at the transplant center or at a referring center

          -  Adequate organ function as measured by:

               1. Cardiac: Left ventricular ejection fraction at rest greater than 40%

               2. Hepatic: Bilirubin less than 2 times the upper limit of normal and alanine
                  transaminase (ALT) and aspartate transaminase (AST) less than 3 times the upper
                  limit of normal

               3. Renal: Creatinine clearance greater than 40 ml/min (measured or
                  calculated/estimated)

               4. Pulmonary: Carbon monoxide diffusion (DLCO), Volume forcibly exhaled in one
                  second (FEV1), and Forced Vital Capacity (FVC) greater than 50% of predicted
                  value (corrected for hemoglobin), or O2 saturation greater than 92% of room air

          -  An adequate autologous graft defined as a cryopreserved PBSC graft containing at least
             4.0 x 106 CD34+ cells/kg patient weight; if prior to enrollment it is known that a
             patient will be on the auto-allo arm (i.e., a consenting, eligible HLA-matched sibling
             donor is available), the required autograft must contain at least 2.0 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; for patients without an HLA-matched sibling
             donor, the autograft must be stored so that there are two products each containing at
             least 2 x 10^6 CD34+ cells/kg patient weight

        Exclusion Criteria:

          -  Never advanced beyond Stage I MM since diagnosis

          -  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)

          -  Plasma cell leukemia

          -  Karnofsky performance score less than 70%, unless approved by the Medical Monitor or
             one of the Protocol Chairs

          -  Uncontrolled hypertension

          -  Uncontrolled bacterial, viral, or fungal infections (currently taking medication and
             progression of clinical symptoms)

          -  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 Medical Monitor or one of the Protocol Chairs; cancer
             treated with curative intent more than 5 years previously will be allowed

          -  Pregnant or breastfeeding

          -  Seropositive for the human immunodeficiency virus (HIV)

          -  Unwilling to use contraceptive techniques during and for 12 months following treatment

          -  Prior allograft or prior autograft

          -  Received mid-intensity melphalan (more than 50 mg IV) as part of prior therapy

          -  Prior organ transplant requiring immunosuppressive therapy