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

Running, not enrolling · Phase 3

Conditions studied: Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Mixed Phenotype Acute Leukemia, Myelodysplastic Syndrome

In brief

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 facts

Study ID

NCT05457556

Run by

Children's Oncology Group

People needed

66

Starts

2023-03-15

Expected to finish

2027-07-07

Last updated by the study team

2026-07-30

Who can join

Age: 1 and older, up to 21. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• PATIENT INCLUSION CRITERIA FOR ENROLLMENT:
• 6 months to < 22 years at enrollment
• Diagnosed with ALL, AML, or MDS or mixed phenotype acute leukemia (MPAL) for which an allogeneic hematopoietic stem cell transplant is indicated. Complete Remission (CR) status will not be confirmed at the time of enrollment. CR as defined in these sections is required to proceed with the actual HCT treatment plan
• Has not received a prior allogeneic hematopoietic stem cell transplant
• Does not have a suitable human leukocyte antigen (HLA)-matched sibling donor available for stem cell donation
• Has an eligible haploidentical related family donor based on at least intermediate resolution HLA typing
• Patients who also have an eligible 8/8 MUD adult donor based on confirmatory high resolution HLA typing are eligible for randomization to Arm A or Arm B.
• Patients who do not have an eligible MUD donor are eligible for enrollment to Arm C
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
• Co-Enrollment on other trials
• Patients will not be excluded from enrollment on this study if already enrolled on other protocols for treatment of high risk and/or relapsed ALL, AML, MPAL and MDS. This is including, but not limited to, COG AAML1831, COG AALL1821, the EndRAD Trial, as well as local institutional trials. We will collect information on all co-enrollments
• Patients will not be excluded from enrollment on this study if receiving immunotherapy prior to transplant as a way to achieve remission and bridge to transplant. This includes chimeric antigen receptor (CAR) T cell therapy and other immunotherapies
• PATIENT INCLUSION CRITERIA TO PROCEED TO HCT:
• Karnofsky Index or Lansky Play-Performance Scale >= 60 on pre-transplant evaluation. Karnofsky scores must be used for patients >= 16 years of age and Lansky scores for patients =< 16 years of age (within 4 weeks of starting therapy)
• A serum creatinine based on age/gender as follows:
• 6 months to < 1 year: 0.5 mg/dL (Male); 0.5 mg/dL (Female)
• to < 2 years: 0.6 mg/dL (Male); 0.6 mg/dL (Female)
• to < 6 years: 0.8 mg/dL (Male); 0.8 mg/dL (Female)
• 6 to < 10 years: 1 mg/dL (Male); 1 mg/dL (Female) 10 to < 13 years: 1.2 mg/dL (Male); 1.2 mg/dL (Female) 13 to < 16 years: 1.5 mg/dL (Male); 1.4 mg/dL (Female) >= 16 years: 1.7 mg/dL (Male); 1.4 mg/dL (Female)
• OR
• A 24 hour urine Creatinine clearance >= 60 mL/min/1.73 m\^2
• OR
• A glomerular filtration rate (GFR) >= 60 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
• Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility

You may not qualify if…

• PATIENT EXCLUSION CRITERIA FOR ENROLLMENT:
• Patients with genetic disorders (generally marrow failure syndromes) prone to secondary AML/ALL/MPAL with known poor outcomes because of sensitivity to alkylator therapy and/or TBI are not eligible (Fanconi Anemia, Kostmann Syndrome, Dyskeratosis Congenita, etc). Patients with Downs syndrome because of increased toxicity with intensive conditioning regimens.
• Patients with any obvious contraindication to myeloablative HCT at the time of enrollment
• Female patients who are pregnant are ineligible as many of the medications used in this protocol could be harmful to unborn children and infants
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
• PATIENT EXCLUSION CRITERIA TO PROCEED TO HCT:
• Patients with uncontrolled fungal, bacterial, viral, or parasitic infections are excluded. Patients with history of fungal disease during chemotherapy may proceed if they have a significant response to antifungal therapy with no or minimal evidence of disease remaining by computed tomography (CT) evaluation
• Patients with active central nervous system (CNS) leukemia or any other active site of extramedullary disease at the time of initiation of the conditioning regimen are not permitted.
• Note: Those with prior history of CNS or extramedullary disease, but with no active disease at the time of pre-transplant workup, are eligible
• Pregnant or breastfeeding females are ineligible as many of the medications used in this protocol could be harmful to unborn children and infants

Where it is running

• Phoenix Childrens Hospital — Phoenix, Arizona, United States
• Arkansas Children's Hospital — Little Rock, Arkansas, United States
• City of Hope Comprehensive Cancer Center — Duarte, California, United States
• Loma Linda University Medical Center — Loma Linda, California, United States
• Children's Hospital Los Angeles — Los Angeles, California, United States
• UCSF Benioff Children's Hospital Oakland — Oakland, California, United States
• Lucile Packard Children's Hospital Stanford University — Palo Alto, California, United States
• UCSF Medical Center-Mission Bay — San Francisco, California, United States
• Children's Hospital Colorado — Aurora, Colorado, United States
• Yale University — New Haven, Connecticut, United States
• Alfred I duPont Hospital for Children — Wilmington, Delaware, United States
• Children's National Medical Center — Washington D.C., District of Columbia, United States
• UF Health Cancer Institute - Gainesville — Gainesville, Florida, United States
• Nemours Children's Clinic-Jacksonville — Jacksonville, Florida, United States
• University of Miami Miller School of Medicine-Sylvester Cancer Center — Miami, Florida, United States
• Nicklaus Children's Hospital — Miami, Florida, United States
• AdventHealth Orlando — Orlando, Florida, United States
• Johns Hopkins All Children's Hospital — St. Petersburg, Florida, United States
• Lurie Children's Hospital-Chicago — Chicago, Illinois, United States
• University of Chicago Comprehensive Cancer Center — Chicago, Illinois, United States
• Riley Hospital for Children — Indianapolis, Indiana, United States
• University of Iowa/Holden Comprehensive Cancer Center — Iowa City, Iowa, United States
• Norton Children's Hospital — Louisville, Kentucky, United States
• Children's Hospital New Orleans — New Orleans, Louisiana, United States
• Children's Hospital of Alabama — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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