Multiple Myeloma Clinical Trial
Stem Cell Transplantation in Individuals With Multiple Myeloma (BMT CTN 0102)
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.
Full Description
Multiple myeloma (MM), characterized by malignant plasma cell proliferation, bone destruction, and immunodeficiency, is a disease with a median age at diagnosis of approximately 65 years. It is responsible for about 1 percent of all cancer-related deaths in Western Countries. Conventional treatments with chemotherapy and radiation therapy are non-curative but improve quality of life and duration of survival. Attempts to cure myeloma through high-dose therapy followed by autografting or allografting have largely failed due to a combination of relapsed disease or transplant related mortality (TRM). High-dose therapy with autologous transplantation is safe and has low TRM (less than 5%), but is associated with a continuing and nearly universal risk of disease progression and relapse. Even so, autologous transplantation is superior to continued conventional chemotherapy. Recent data indicate that tandem autologous transplants are superior to a single procedure. Even with this approach, patients remain at risk of relapse and additional approaches are needed.
DESIGN NARRATIVE:
The overall study design is that of biologic assignment, based on the availability of an HLA-matched sibling, to one of two treatment strategies for MM patients. Patients without an HLA-matched sibling will undergo tandem autologous transplants. Patients with an HLA-matched sibling will undergo an autologous transplant followed by a non-myeloablative allogeneic transplant. In addition, the tandem autologous transplant recipients will be randomized to either observation or one year of maintenance therapy to begin following the second autologous transplant. The large number of MM patients without an HLA-matched sibling enables us to evaluate the role of maintenance therapy following tandem autologous transplants.
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:
Cardiac: Left ventricular ejection fraction at rest greater than 40%
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
Renal: Creatinine clearance greater than 40 ml/min (measured or calculated/estimated)
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
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There are 35 Locations for this study
Birmingham Alabama, 35294, United States
Phoenix Arizona, 85006, United States
Duarte California, 91010, United States
La Jolla California, 92037, United States
La Jolla California, 92093, United States
Stanford California, 94305, United States
Denver Colorado, 80218, United States
Gainesville Florida, 32610, United States
Atlanta Georgia, 30322, United States
Atlanta Georgia, 30342, United States
Maywood Illinois, 60156, United States
Indianapolis Indiana, 46237, United States
Wichita Kansas, 67214, United States
Boston Massachusetts, 02111, United States
Boston Massachusetts, 02114, United States
Ann Arbor Michigan, 48109, United States
Minneapolis Minnesota, 55455, United States
Omaha Nebraska, 68198, United States
Hackensack New Jersey, 07601, United States
New York New York, 10021, United States
Durham North Carolina, 27710, United States
Cincinnati Ohio, 45236, United States
Cleveland Ohio, 44106, United States
Oklahoma City Oklahoma, 73104, United States
Portland Oregon, 97239, United States
Philadelphia Pennsylvania, 19104, United States
Philadelphia Pennsylvania, 19111, United States
Nashville Tennessee, 37232, United States
Houston Texas, 77030, United States
Houston Texas, 77030, United States
San Antonio Texas, 78229, United States
Salt Lake City Utah, 84132, United States
Richmond Virginia, 23298, United States
Seattle Washington, 98109, United States
Madison Wisconsin, 53792, United States
Milwaukee Wisconsin, 53226, United States
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