Mismatched Related Donor Versus Matched Unrelated Donor Stem Cell Transplantation for Children, Adolescents, and Young Adults With Acute Leukemia or Myelodysplastic Syndrome

Conditions

• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Mixed Phenotype Acute Leukemia
• Myelodysplastic Syndrome

Eligibility Criteria

Sex

ALL

Age

6 Months - 21 Years

Healthy Volunteers

Not accepted

Interventions

• Biospecimen Collection — PROCEDURE
  Undergo collection of blood
• Bone Marrow Aspiration — PROCEDURE
  Undergo bone marrow aspiration
• Busulfan — DRUG
  Given intravenously (IV)
• Cyclophosphamide — DRUG
  Given IV
• Echocardiography Test — PROCEDURE
  Undergo ECHO
• Fludarabine — DRUG
  Given IV
• Haploidentical Hematopoietic Cell Transplantation — PROCEDURE
  Undergo haploHCT
• Lapine T-Lymphocyte Immune Globulin — BIOLOGICAL
  Given IV
• Lumbar Puncture — PROCEDURE
  Undergo lumbar puncture
• Matched Unrelated Donor Hematopoietic Cell Transplantation — PROCEDURE
  Undergo MUD-HCT
• Melphalan — DRUG
  Given IV
• Methotrexate — DRUG
  Given IV
• Multigated Acquisition Scan — PROCEDURE
  Undergo MUGA
• Mycophenolate Mofetil — DRUG
  Given IV
• Myeloablative Conditioning — PROCEDURE
  Receive myeloablative conditioning regimen
• Quality-of-Life Assessment — OTHER
  Ancillary studies
• Questionnaire Administration — OTHER
  Ancillary studies
• Rituximab — BIOLOGICAL
  Given IV
• T-Cell Depletion Therapy — PROCEDURE
  Undergo haploHCT with alpha beta T cell depletion
• Tacrolimus — DRUG
  Given IV
• Thiotepa — DRUG
  Given IV
• Total-Body Irradiation — RADIATION
  Undergo TBI

Study Details

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 and/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. 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.

Key Dates

Start date

Mar 15, 2023

Status verified

May 2025

Primary completion

Jun 30, 2026

Completion

Jun 30, 2026

Study Design

Enrollment

435 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Arm A (halploHCT)
  Patients receive a myeloablative conditioning regimen with PTCy or alpha beta T cell depletion at the discretion of the treating provider. Patients then undergo haploHCT on day 0. Patients undergoing myeloablative conditioning regimen with PTCy also receive GVHD prophylaxis on days 3-5. Patients undergo lumbar puncture, bone marrow aspiration, and ECHO or MUGA during screening. Patients also undergo collection of blood throughout the trial.
• Experimental: Arm B (MUD-HCT)
  Patients receive a TBI-based or chemotherapy-based myeloablative conditioning regimen between days -9 and -2, followed by MUD-HCT on day 0. Patients then receive GVHD prophylaxis regimen on days 1-11. Patients undergo lumbar puncture, bone marrow aspiration, and ECHO or MUGA during screening. Patients also undergo collection of blood throughout the trial.
• Experimental: Arm C (haploHCT)
  Patients who only have a haplo donor receive a myeloablative conditioning regimen with PTCy or alpha beta T cell depletion at the discretion of the treating provider. Patients then undergo haploHCT on day 0. Patients undergoing myeloablative conditioning regimen with PTCy also receive GVHD prophylaxis on days 3-5. Patients undergo lumbar puncture, bone marrow aspiration, and ECHO or MUGA during screening. Patients also undergo collection of blood throughout the trial.

Primary Outcome Measure

Severe GVHD (Grade III-IV acute GVHD or chronic GVHD requiring systemic immunosuppressive therapy) [ Time Frame: Up-to 1-year post hematopoietic cell transplantation (HCT) ]

Locations (57)

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