Pamela S. Becker, MD, PhD
Dr. Becker is a Joint Associate Member at the Fred Hutchinson Cancer
Research Center, which is a Core Clinical Center of the Blood and Marrow
Transplant Clinical Trials Network.
Study Title: A Multi-Center, Phase III, Randomized Trial of Reduced Intensity Conditioning (RIC) and Transplantation of Double Unrelated Umbilical Cord Blood (dUCB) Versus HLA-Haploidentical Related Bone Marrow (Haplo-BM) for Patients With Hematologic Malignancies (BMT CTN #1101)
Clinical Trials.gov Identifier: NCT01597778
Sponsor: Medical College of Wisconsin
Collaborators: National Heart, Lung, and Blood Institute (NHLBI), National Cancer Institute (NCI), and Blood and Marrow Transplant Clinical Trials Network (BMT CTN)
Participating Centers: 15 core study participants (consortium or individual institutions) of the BMT CTN and 15 affiliate study participants
Accrual Goal: 410 patients
Study Design: This is a multicenter, phase III, randomized trial. The primary objective is to compare progression-free survival (PFS) at two years postrandomization. Patients in both study groups undergo the same RIC preparative regimen. Post-conditioning, patients in one randomized group receive unrelated double cord blood units as the stem cell source while the other receives HLA-haploidentical bone marrow. Secondary objectives include comparison of neutrophil and platelet recovery time, rates of primary and secondary graft failure, donor cell engraftment, incidence of acute and chronic graft-versus-host disease (GVHD), overall survival, treatment-related mortality, relapse rates, incidence of disease progression, number of hospital admissions and length of stay, quality of life, and cost effectiveness. Patients ages 18 to 70 are eligible if they have both of the following: one or more related haploidentical donors and at least two identified umbilical cord blood units of sufficient size matched at a minimum of 4/6 HLA loci. Patients with the following diagnoses are included in the study: intermediate- or poor-risk acute lymphocytic or myeloid leukemia in first complete remission (CR); acute leukemia or Burkitt lymphoma in ≥ second CR; biphenotypic, undifferentiated, or prolymphocytic leukemia; adult T-cell leukemia/lymphoma in CR; and lymphomas fulfilling certain study-defined criteria.
Rationale: One-third of patients eligible for allogeneic stem cell transplant lack a suitable HLA-matched related or unrelated donor. Previous studies showed that the outcome of transplant in adults using single cord blood units as the donor source was inferior to that using haploidentical bone marrow. To address further the efficacy and safety of alternative donor transplants, two parallel phase II trials were conducted that used similar reduced-intensity preparative regimens followed by transplant using either haploidentical bone marrow (NCT00849147; BMT CTN 0603) or double umbilical cord blood units (NCT00864227; BMT CTN 0604) as the stem cell source. Both trials had the same objectives, eligibility criteria, and clinical endpoints, and each enrolled 50 patients. The outcomes were comparable with those using HLA-matched, unrelated donors, and because the data showed similar survival, neutrophil recovery time, and rates of GVHD for the two alternative donor approaches, the stage was set for the current randomized trial.
Comment: Allogeneic stem cell transplantation is the only curative therapy for several hematologic malignancies, but the inability to identify a suitable HLA-matched donor in a timely manner can preclude the use of this potentially lifesaving procedure. Sequential clinical trials have led to the refinement of successful approaches using alternative donor sources, either combined cord blood units or haploidentical-related family members. This pivotal trial is powered to detect a 15 percent increase in PFS at two years. Given the resources required to support each of these transplant approaches and the potential to cure life-threatening disorders, it is essential to learn whether one is superior to the other using criteria including longer survival, less toxicity, better quality of life, and lower cost.
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