Title
A Multi-Center, Phase 3, Randomized Trial of Matched Unrelated Donor (MUD) versus HLA-Haploidentical Related (Haplo) Myeloablative Hematopoietic Cell Transplantation for Children, Adolescents, and Young Adults (AYA) with Acute Leukemia or Myelodysplastic Syndrome (MDS)

Description
This phase III trial compares hematopoietic (stem) cell transplantation (HCT) using mismatched related donors (haploidentical [haplo]) versus matched unrelated donors (MUD) in treating children, adolescents, and young adults with acute leukemia or myelodysplastic syndrome (MDS). HCT is considered standard of care treatment for patients with high-risk acute leukemia and MDS. In HCT, patients are given very high doses of chemotherapy or radiation therapy, which is intended to kill cancer cells that may be resistant to more standard doses of chemotherapy; unfortunately, this also destroys the normal cells in the bone marrow, including stem cells. After the treatment, patients must have a healthy supply of stem cells reintroduced or transplanted. The transplanted cells then reestablish the blood cell production process in the bone marrow. The healthy stem cells may come from the blood or bone marrow of a related or unrelated donor. If patients do not have a matched related donor, doctors do not know what the next best donor choice is or if a haplo related donor or MUD is better. This trial may help researchers understand whether a haplo related donor or a MUD HCT for children with acute leukemia or MDS is better or if there is no difference at all.

Objective
PRIMARY OBJECTIVE:

I. To compare the 1-year cumulative incidence of severe Graft Versus Host Disease (GVHD) (from day of HCT) defined as grade III-IV acute GVHD (aGVHD) and/or chronic GVHD (cGVHD) that requires systemic immunosuppression and to compare the disease free survival (DFS) (from time of randomization) in children and young adults (AYA) with acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), and myelodysplastic syndrome (MDS) who are randomly assigned to haploHCT or to an 8/8 adult MUD-HCT.

SECONDARY OBJECTIVES:

I. To compare overall survival (OS) between children and AYA with AML/ALL/MDS randomly assigned to haploHCT and MUD HCT.

II. To compare differences in health-related quality of life (HRQOL) between haploHCT and MUD HCT from baseline (pre-transplant), at 6 months, 1 year and 2 years post-transplant.

Treatment Timing of consent should be at the discretion of the site i.e. when it is convenient and best for the patient. We encourage centers to consent their patients at the time it is recognized they need a HCT. Patients with both available donor sources (8/8 MUD and haplo) will be randomized to Arm A (haploHCT) or Arm B (MUD HCT). We anticipate this consent will be while a patient is receiving chemotherapy. Enrollment and randomization should occur only when the site is ready to acquire a donor. The randomization will be stratified by patient age, CR status, and disease type. Patients enrolled on this study who only have an available haplo donor will be assigned to Arm C and receive a nonrandomized haploHCT. We anticipate it will take at least 4 weeks from the time of randomization until the patient begins the HCT myeloablative conditioning regimen. A patient must meet eligibility for HCT within 12 weeks of randomization or they will be removed from the study protocol therapy.

Key Eligibility For full study eligibility see this study's ClinicalTrials.gov record.

Applicable Disease Sites
Hematologic cancers, other; Leukemia

Participating Institutions
Gundersen Health System; UW Health University Hospital