Blood and Marrow Transplant Clinical Trials Network (BMT CTN) A Randomized, Multi-Center, Phase III Study of Allogeneic Stem Cell Transplantation Comparing Regimen Intensity in Patients with Myelodysplastic Syndrome or Acute Myeloid Leukemia (0901)
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Open BioLINCC Study See bottom of this webpage for request information
May 2011 – January 2017
Dataset(s) Last Updated
March 5, 2021
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To determine if reduced-intensity conditioning (RIC) would result in improved overall survival (OS) given the lower treatment-related mortality (TRM) compared with myeloablative conditioning (MAC).
Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are predominantly diseases of older patients. Currently, the only strategy that offers a cure is allogenic hematopoietic cell transplantation (HCT). However, many patients do not undergo HCT because of advanced age or unacceptable risks associated with HCT. One risk is TRM due to toxicity from pre-transplant MAC. In recent years, RIC regimens were introduced in an attempt to reduce TRM. Age is one of many factors considered to select for RIC versus MAC, thus complicating the interpretation of previous nonrandomized studies. Consequently, the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) conduced a phase III randomized trial comparing RIC and MAC in patients with AML or MDS.
Eligible participants had a World Health Organization defined diagnosis of AML or MDS, were receiving a first HCT, and had <5% marrow myeloblasts pre-HCT. Patients were 18-65 years of age, had an HLA-A, -B, and -DRB1 (6/6) matched sibling donor, or a ≥7/8 HLA-A, -B, -C, and -DRB1 matched unrelated donor, and a HCT-comorbidity index (CI) ≤ 4. In AML, a composite definition of high risk included unfavorable risk cytogenetics according to the ECOG/SWOG cytogenetic classification schema, presence of FLT3 mutation regardless of cytogenetic abnormalities or patients who are in their third or greater complete remission. High-risk MDS was defined as patients with intermediate-II or high risk disease per the International Prognostic Scoring System. A total of 272 patients were enrolled at 32 sites, 135 patients were randomly assigned to MAC and 137 patients were randomly assigned to RIC. Planned enrollment was higher, however, accrual ceased due to high relapse incidence with RIC versus MAC.
BMT CTN-0901 was a phase III randomized clinical trial with participants randomized 1:1 to receive either RIC or MAC. Patients and physicians were informed of the randomization. However, study investigators assigned to evaluate endpoints were blinded to each participant’s randomization.
Patients randomized to RIC received one of two regimen types: fludarabine (120 to 180 mg/m2) with busulfan (≤ 8 mg/kg orally or 6.4 mg/kg intravenously; Flu/Bu2) or fludarabine (120-180 mg/m2) with melphalan (≤150 mg/m2; Flu/Mel). Patients randomized to MAC received one of three regimens: busulfan (16 mg/kg orally or 12.8 mg/kg intravenously) with cyclophosphamide (120 mg/kg); or busulfan (16 mg/kg orally or 12.8 mg/kg intravenously) with fludarabine (120-180 mg/m2; Flu/Bu4); or cyclophosphamide (120 mg/kg) and total body irradiation (12 to 14.2 Gy). Graft-versus-host disease (GVHD) prophylaxis included methotrexate in combination with other drugs. Stem-cell sources were bone marrow or peripheral-blood stem cells. Supportive care included growth factors and transfusion support. In addition to regular clinic visits, patients had study-related visits weekly for the first 12 weeks and at 100 days, 6 months, and 12 months. Bone marrow aspirates or biopsies were performed at 100 days, 18 months, and as clinically indicated. Toxicity assessments occurred at days 28, 56, and 100 and at 6, 12, and 18 months.
The primary endpoint was OS difference at 18 months post-random assignment. Secondary endpoints included relapse-free survival, TRM, absolute neutrophil count and platelet recovery, kinetics of donor-cell engraftment, graft failure, GVHD, grade 3 to 4 toxicities, infections, and quality of life.
OS was higher with MAC, but this was not statistically significant. RIC resulted in lower TRM but higher relapse rates compared to MAC, with a statistically significant advantage in RFS with MAC. The accrual of patients was halted because of ethical concerns over higher than expected relapse rates in patients receiving RIC. These data support the use of MAC as the standard of care for fit patients with AML or MDS.
Scott BL, Pasquini MC, Logan BR, et al. Myeloablative Versus Reduced-Intensity Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes. J Clin Oncol. 2017;35(11):1154–1161. doi:10.1200/JCO.2016.70.7091
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Resources AvailableStudy Datasets Only
- Data Dictionary (PDF - 1.1 MB)
- BMT 0901 Case Report Forms (PDF - 3.2 MB)
- BMT 0901 Protocol (PDF - 2.2 MB)
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