This randomized phase II trial studies how well a partially matched (haploidentical) donor stem cell transplant and umbilical cord blood transplant works compared to a matched unrelated (not a sibling or family member) stem cell donor in treating patients with acute myeloid leukemia or myelodysplastic syndrome that is likely to recur (come back), or spread (high-risk). When matched family members cannot be identified, doctors use the stem cells of other healthy volunteers whose blood type matches the patients' blood. Another transplant procedure uses stem cells from umbilical cord blood (UCB) from the placenta of newborn baby. Chemotherapy and total-body irradiation are given before transplant to help stop the growth of cancer cells in the bone marrow and weaken the immune system so that the transplant cells can grow. It may take time to find a donor who is not a family member but matches the patient's blood type. Giving an umbilical cord blood transplant with a partially matched stem cell transplant may be as effective as a matched stem cell transplant in treating patients with acute myeloid leukemia or high-risk myelodysplastic syndrome.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02648932.
PRIMARY OBJECTIVES:
I. To compare time from formal search to hematopoietic cell transplantation (HCT) for patients 18 years and older, randomized between haploidentical (haplo)-cord search and matched unrelated donor (MUD) search for patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS).
SECONDARY OBJECTIVES:
I. To compare the percentage of patients who undergo HCT in each study cohort.
II. To evaluate overall survival from time to randomization by study cohort.
III. For those undergoing transplant compare outcomes by donor type received MUD versus (vs) haplo-cord for neutrophil engraftment, grade 3-5 day 100 toxicities and chimerism.
IV. To evaluate non-relapse mortality, rates of acute and chronic graft-versus-host disease (GVHD), leukemia-free survival and overall survival by donor type.
V. To collect correlative samples for future research.
OUTLINE:
CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -7 to -3, busulfan IV on days -6 to - 3, and anti-thymocyte globulin IV on days - 5, -3, and -1. Patients >= 55 years of age and Karnofsky performance status (KPS) 80%, and/or HCT-comorbidity index score or 4 or more, do not receive busulfan. These patients receive melphalan IV on day -2 and may undergo total body irradiation (TBI) on days -2 and -1 per treating physician recommendation.
ALLOGENEIC STEM CELL TRANSPLANT: Patients are randomized to 1 of 2 treatment arms.
ARM A (HAPLO-CORD): Patients undergo haploidentical hematopoietic stem cell transplant (HSCT) on day 0 and UBC stem cell transplant on day 1.
ARM B (MUD): Patients undergo MUD HSCT on day 0 or 1.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously over 24 hours or over 3 hours every 12 hours or orally (PO) beginning on day -2 to day 180 and then tapered every week thereafter, and mycophenolate mofetil every 8 hours on day -2 to 28.
After completion of study treatment, patients are followed up at 4 and 7 weeks, 100 days, and then at 6, 12, 24, and 36 months.
Lead OrganizationUniversity of Chicago Comprehensive Cancer Center
Principal InvestigatorAndrew Saul Artz
