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Brief Title: Acute Myeloid Leukemia T Cell Depletion to Improve Transplants in Adults With Acute Myeloid Leukemia (BMT CTN 0303)
Official Title: A Phase 2 Single Arm Trial of HLA-Matched Transplants, CD34+ Enriched, T-Cell Depleted Peripheral Blood Stem Cells Isolated by CliniMACS System in the Treatment of Patients With AML in 1st or 2nd Morphologic Complete Remission (BMTCTN0303)
Study ID: NCT00201240
Brief Summary: This study is a single arm Phase II, multicenter trial. It is designed to determine whether the anticipated endpoints for a T cell depleted transplant arm of a planned prospective randomized trial comparing T cell depleted and unmodified hematopoietic allografts are likely to be achieved in a multicenter study conducted by the Blood and Marrow Transplant Clinical Trials Network (BMT CTN or Network). The study population is patients with acute myeloid leukemia (AML) in first or second morphologic complete remission. The enrollment is 45 patients. Based on published results of unmodified transplants from HLA-matched siblings applied to patients with AML in first or second morphologic complete remission, a significant improvement in results with a graft modified as specified in this protocol would be expected if disease-free survival (DFS) at 6 months was greater than 75%, the true incidence of transplant-related mortality at 1 year was less than 30%, and the DFS rate at 2 years was greater 70% for patients transplanted in first remission and less than 60% for patients transplanted in second remission. Additional secondary endpoints include the following: graft failure rate and incidences of acute grade II-IV and chronic graft-versus-host disease (GVHD). Additionally, the trial will have target specific doses of CD34+ progenitors and CD3+ T cells to be obtained following fractionation with the CliniMACS system. Based on the results of this trial, a Phase III trial comparing T cell depleted peripheral blood stem cell transplants (PBSCT) with unmanipulated bone marrow or unmanipulated PBSCT will be designed.
Detailed Description: BACKGROUND: Allogeneic hematopoietic cell transplantation is an accepted therapy for AML. Transplants of unmodified HLA-matched related bone marrow or peripheral blood stem cells following conditioning with total body irradiation (TBI) and cyclophosphamide or VP-16 or busulfan and cyclophosphamide have led to sustained DFS rates of 45-60% for adults transplanted in first complete remission (CR1) and 40-53% for patients transplanted in second complete remission (CR2). In several single center and multicenter cooperative group prospective trials comparing HLA-matched allogeneic transplants to chemotherapy in the treatment of AML in CR1, DFS rates for the transplant arm were almost invariably superior; however, these advantages were statistically significant in only a minority of the cooperative group studies conducted. In each study, the risk of relapse was significantly lower for patients receiving allogeneic transplants. However, this advantage was counterbalanced by transplant-related mortality, principally reflecting infections complicating GVHD and its treatment. DESIGN NARRATIVE: Despite increased risks of infection, development of effective T cell depletion (TCD) techniques for prevention of GVHD and tolerable modifications of regimens for pre-transplant cytoreduction that secure consistent engraftment offer the potential for significant decreases in transplant-related mortality. Furthermore, the use of TCD transplants in the treatment of patients with AML is not associated with substantial increases in the incidence of relapse. Several single center trials indicate highly encouraging long-term results, particularly for patients with AML in CR1 or CR2. Although the number of cases in each single center series is limited, the consistency of the results suggests that the use of an effective technique for TCD together with an adequate cytoreductive regimen might yield transplant results superior to those achieved with unmodified grafts.
Minimum Age: 18 Years
Eligible Ages: ADULT, OLDER_ADULT
Sex: ALL
Healthy Volunteers: No
City of Hope National Medical Center, Duarte, California, United States
University of California, San Francisco, San Francisco, California, United States
Dana Farber Cancer Institute/Brigham & Women's Hospital, Boston, Massachusetts, United States
Memorial Sloan-Kettering Cancer Center, New York, New York, United States
University Hospitals of Cleveland/Case Western, Cleveland, Ohio, United States
Ohio State/Arthur G. James Cancer Hospital, Columbus, Ohio, United States
University of Pennsylvania Cancer Center, Philadelphia, Pennsylvania, United States
Medical College of Wisconsin, Milwaukee, Wisconsin, United States
Name: Steven Devine, MD
Affiliation: Ohio State/Arthur G. James Cancer Hospital
Role: STUDY_CHAIR
Name: Parameswaran Hari, MD
Affiliation: Medical College of Wisconsin
Role: PRINCIPAL_INVESTIGATOR
Name: Hillard Lazarus, MD
Affiliation: University Hospitals of Cleveland/Case Western
Role: PRINCIPAL_INVESTIGATOR
Name: Lloyd Damon, MD
Affiliation: University of California, San Francisco
Role: PRINCIPAL_INVESTIGATOR
Name: Richard O'Reilly, MD
Affiliation: Memorial Sloan Kettering Cancer Center
Role: STUDY_CHAIR
Name: Robert Soiffer, MD
Affiliation: Dana Farber Cancer Institute/Brigham & Women's Hospital
Role: PRINCIPAL_INVESTIGATOR
Name: Anthony Stein, MD
Affiliation: City of Hope National Medical Center
Role: PRINCIPAL_INVESTIGATOR
Name: John DiPersio, MD, PhD
Affiliation: Washington University/Barnes Jewish Hospital
Role: PRINCIPAL_INVESTIGATOR
Name: Edward Stadtmauer, MD
Affiliation: University of Pennsylvania
Role: PRINCIPAL_INVESTIGATOR