AzTrials
AzTrials

Acute Lymphoblastic LeukemiaPhase 3NCT05457556

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

A Phase 3 study testing Biospecimen Collection, Bone Marrow Aspiration and Busulfan in people with Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia, run by Children's Oncology Group at 63 sites in 3 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 6 months to 21 years
What is being tested?
Biospecimen Collection, Bone Marrow Aspiration and Busulfan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
66 participants
Where
63 sitesin 3 countries
Study dates
15 Mar 2023to 7 Jul 2027
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 months to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
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  • 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
  • Serum glutamic-oxaloacetic transaminase (SGOT) aspartate aminotransferase [AST] or serum glutamate pyruvate transaminase (SGPT) aminotransferase [ALT] < 5 x upper limit of normal (ULN) for age
  • Total bilirubin < 2.5 mg/dL, unless attributable to Gilbert's Syndrome
  • Shortening fraction of >= 27% by echocardiogram or radionuclide scan (MUGA)
  • OR
  • Ejection fraction of >= 50% by echocardiogram or radionuclide scan (MUGA), choice of test according to local standard of care
  • Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and corrected carbon monoxide diffusing capability (DLCO) must all be >= 50% of predicted by pulmonary function tests (PFTs).
  • For children who are unable to perform for PFTs (e.g., due to age or developmental delay), the criteria are: no evidence of dyspnea at rest, oxygen (O2) saturation (Sat) > 92% on room air by pulse oximetry, not on supplemental O2 at rest, and not on supplemental O2 at rest
  • MPAL in first complete remission (CR1) for whom transplant is indicated. Examples include those patients who are poorly responsive to ALL therapy (end of induction failure( IF-MPAL) to ALL induction (see IF-MPAL note below), end of induction MRD ≥ 5% or end-of-consolidation MRD > 0.01%), as well as patients treated with AML therapy
  • IF-MPAL: additional criterion for Induction failure for MPAL ONLY as per ALL1732:
  • An increasing number of circulating leukemia cells on 3 or more consecutive CBCs obtained at daily or longer intervals following day 8 of Induction therapy and prior to day 29 with confirmation by flow cytometry OR development of new sites of extramedullary disease, or other laboratory or clinical evidence of refractory disease or progression prior to the end of Induction evaluation (note that residual testicular disease at the end of Induction is an exception)
  • MPAL in > second complete remission (CR2)
  • ALL high-risk in CR1 for whom transplant is indicated. Examples include: induction failure, treatment failure as per minimal residual disease by flow cytometry > 0.01% after consolidation and not eligible for AALL1721 or AALL1721 not available/unwilling to enroll, hypodiploidy (< 44 chromosomes) with MRD+ > 0.01% after induction, persistent or recurrent cytogenetic or molecular evidence of disease during therapy requiring additional therapy after induction to achieve remission (e.g. persistent molecular BCR-ABL positivity), T cell ALL with persistent MRD > 0.01% after consolidation.
  • ALL in CR2 for whom transplant is indicated. Examples include: B-cell: early (=< 36 months from initiation of therapy) bone marrow (BM) relapse, late BM relapse (>= 36 months) with MRD >= 0.1% by flow cytometry after first re-induction therapy; T or B-cell: early (< 18 months) isolated extramedullary (IEM), late (>= 18 months) IEM, end-Block 1 MRD >= 0.1%; T-cell or Philadelphia chromosome positive (Ph+): BM relapse at any time
  • ALL in >= third complete remission (CR3)
  • Patients treated with chimeric antigen receptor T-cells (CART) cells for whom transplant is indicated. Examples include: transplant for consolidation of CART, loss of CART persistence and/or B cell aplasia < 6 months from infusion or have other evidence (e.g., MRD+) that transplant is indicated to prevent relapse
  • AML in CR1 for whom transplant is indicated. Examples include those deemed high risk for relapse as described in AAML1831:
  • FLT3/ITD+ with allelic ratio > 0.1 without bZIP CEBPA, NPM1
  • FLT3/ITD+ with allelic ratio > 0.1 with concurrent bZIP CEBPA or NPM1 and with evidence of residual AML (MRD >= 0.05%) at end of Induction
  • Presence of RAM phenotype or unfavorable prognostic markers (other than FLT3/ITD) per cytogenetics, fluorescence in situ hybridization (FISH), next generation sequencing (NGS) results, regardless of favorable genetic markers, MRD status or FLT3/ITD mutation status
  • AML without favorable or unfavorable cytogenetic or molecular features but with evidence of residual AML (MRD >= 0.05%) at end of Induction
  • Presence of a non-ITD FLT3 activating mutation and positive MRD (>= 0.05%) at end of Induction 1 regardless of presence of favorable genetic markers.
  • AML in >= CR2
  • MDS with < 5% blasts by morphology and flow cytometry (if available) on the pre-transplant bone marrow evaluation
  • Complete remission (CR) is defined as < 5% blasts by morphology and flow cytometry (if available) on the pre-transplant bone marrow evaluation with minimum sustained absolute neutrophil count (ANC) of 300 cells/microliter for 1 week or ANC > 500 cells/microliter. We will be collecting data from all approaches to MRD evaluation performed including NGS and polymerase chain reaction (PCR). It is strongly recommended that MPAL be evaluated using multidimensional flow cytometry and/or (KMT2Ar) qt PCR. It is strongly recommended that MPAL be evaluated using multidimensional flow cytometry and/or (KMT2Ar) qt PCR
  • DONOR ELIGIBILITY CRITERIA:
  • Matched Unrelated Donors:
  • Unrelated donor candidates must be matched at high resolution at a minimum of 8/8 alleles (HLA-A, -B, -C, -DRB1). One-antigen HLA mismatches are not permitted. HLA matching of additional alleles is recommended according to National Marrow Donor Program (NMDP) guidelines, but will be at the discretion of local centers
  • Haploidentical Matched Family Members:
  • Minimum match level full haploidentical (at least 5/10; HLA-A, -B, -C, -DRB1, -DQB1 alleles). The following issues (in no particular order) should be considered in choosing a haploidentical donor:
  • Absent or low patient donor-specific antibodies (DSA)
  • Mean fluorescence intensity (MFI) of any anti-donor HLA antibody by solid phase immunoassay should be < 2000. Donors with higher levels are not eligible.
  • If a screening assay against pooled HLA antigens is used, positive results must be followed with specificity testing using a single antigen assay. The MFI must be < 2000 unless the laboratory has validated higher threshold values for reactivity for HLA antigens (such as HLA-C, -DQ, and -DP), that may be enhanced in concentration on the single antigen assays. Donor anti- recipient antibodies are of unknown clinical significance and do not need to be sent or reported.
  • Consult with Study Chair for the clinical significance of any recipient anti-donor HLA antibody.
  • If centers are unable to perform this type of testing, please contact the Study Chair to make arrangements for testing.
  • If killer immunoglobulin testing (KIR) is performed: KIR status by mismatch, KIR-B, or KIR content criteria can be used according to institutional guidelines.
  • ABO compatibility (in order of priority):
  • Compatible or minor ABO incompatibility
  • Major ABO incompatibility
  • CMV serostatus:
  • For a CMV seronegative recipient: the priority is to use a CMV seronegative donor when feasible
  • For a CMV seropositive recipient: the priority is to use a CMV seropositive donor when feasible
  • Age: younger donors including siblings/half-siblings, and second degree relatives (aunts, uncles, cousins) are recommended, even if < 18 years
  • Size and vascular access appropriate by center standard for peripheral blood stem cell (PBSC) collection if needed
  • Haploidentical matched family members: screened by center health screens and found to be eligible
  • Unrelated donors: meet eligibility criteria as defined by the NMDP or other unrelated donor registries. If the donor does not meet the registry eligibility criteria but an acceptable eligibility waiver is completed and signed per registry guidelines, the donor will be considered eligible for this study
  • Human immunodeficiency virus (HIV) negative
  • Not pregnant
  • MUD donors and post-transplant cyclophosphamide haplo donors should be asked to provide BM. If donors refuse and other donors are not available, PBSC is allowed. TCR-alpha beta/CD19 depleted haplo donors must agree to donate PBSC
  • Must give informed consent:
  • Haploidentical matched family members: Institution standard of care donor consent and Protocol-specific Donor Consent for Optional Studies
  • Unrelated donors: standard NMDP Unrelated Donor Consent

Who cannot join

  • 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:
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  • 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

Trial locations and contacts

63 sites in 3 countries.

63 sites in 3 countries

United States57 sites

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48109

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina, 28203

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois, 60611

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Medical City Dallas Hospital

    Dallas, Texas, 75230

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Children's Hospital of Michigan

    Detroit, Michigan, 48201

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Cook Children's Medical Center

    Fort Worth, Texas, 76104

  • UF Health Cancer Institute - Gainesville

    Gainesville, Florida, 32610

  • Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

    Grand Rapids, Michigan, 49503

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Penn State Children's Hospital

    Hershey, Pennsylvania, 17033

  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

    Houston, Texas, 77030

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Nemours Children's Clinic-Jacksonville

    Jacksonville, Florida, 32207

  • Children's Mercy Hospitals and Clinics

    Kansas City, Missouri, 64108

  • Arkansas Children's Hospital

    Little Rock, Arkansas, 72202-3591

  • Loma Linda University Medical Center

    Loma Linda, California, 92354

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • Norton Children's Hospital

    Louisville, Kentucky, 40202

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin, 53792

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • Nicklaus Children's Hospital

    Miami, Florida, 33155

  • The Children's Hospital at TriStar Centennial

    Nashville, Tennessee, 37203

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Yale University

    New Haven, Connecticut, 06520

  • The Steven and Alexandra Cohen Children's Medical Center of New York

    New Hyde Park, New York, 11040

  • Children's Hospital New Orleans

    New Orleans, Louisiana, 70118

  • Laura and Isaac Perlmutter Cancer Center at NYU Langone

    New York, New York, 10016

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • UCSF Benioff Children's Hospital Oakland

    Oakland, California, 94609

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • AdventHealth Orlando

    Orlando, Florida, 32803

  • Lucile Packard Children's Hospital Stanford University

    Palo Alto, California, 94304

  • Phoenix Childrens Hospital

    Phoenix, Arizona, 85016

  • VCU Massey Comprehensive Cancer Center

    Richmond, Virginia, 23298

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • University of Rochester

    Rochester, New York, 14642

  • Primary Children's Hospital

    Salt Lake City, Utah, 84113

  • Methodist Children's Hospital of South Texas

    San Antonio, Texas, 78229

  • UCSF Medical Center-Mission Bay

    San Francisco, California, 94158

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Johns Hopkins All Children's Hospital

    St. Petersburg, Florida, 33701

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467

  • New York Medical College

    Valhalla, New York, 10595

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

  • Alfred I duPont Hospital for Children

    Wilmington, Delaware, 19803

Other trials in United States

Canada5 sites

  • Alberta Children's Hospital

    Calgary, Alberta, T3B 6A8

  • Centre Hospitalier Universitaire Sainte-Justine

    Montreal, Quebec, H3T 1C5

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

  • British Columbia Children's Hospital

    Vancouver, British Columbia, V6H 3V4

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

Australia1 site

  • The Children's Hospital at Westmead

    Westmead, New South Wales, 2145

Other trials in Australia

About this study

Official 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)

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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), mixed phenotype acute leukemia (MPAL), and myelodysplastic syndrome (MDS) who are randomly assigned to haploHCT or to an 8/8 adult MUD-HCT.

SECONDARY OBJECTIVES:

  1. To compare overall survival (OS) between children and AYA with AML/ALL/MPAL/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.

EXPLORATORY OBJECTIVES:

  1. To compare the median time to engraftment and cumulative incidences of neutrophil engraftment at 30 and 100 days post transplant and platelet engraftment at 60 and 100 days post transplant, primary graft failure by 60 days, secondary graft failure at 1 year post transplant, Grade II-IV and III-IV acute graft versus host disease (aGVHD) requiring systemic immunosuppression at 100 days and 6 months, and cumulative incidences of transplant-related mortality (TRM), relapse, and moderate and severe chronic graft versus host disease (cGVHD) at 6 months, 1 and 2 years after haploHCT and MUD HCT.

II. To estimate 1 year, 18-month and 2-year cumulative incidence of graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) with events defined as occurrence of any of the following from Day 0 of HCT: Grade III-IV acute GVHD, chronic GVHD requiring systemic immunosuppressive treatment, disease relapse or progression, and death from any cause.

IIa. To compare "chronic GVHD" (GRFS) after haploHCT and MUD HCT using landmark definitions.

IIb. To compare "current" GRFS is defined as the time to onset of any of the following events from Day 0 of HCT: Grade III-IV acute GVHD, chronic GVHD that is STILL requiring systemic immunosuppressive treatment, disease relapse or progression, death from any cause at 18 months and 2 years.

III. To evaluate the influence of key clinical variables: age (<13 years and 13-21.99 years), disease (ALL/MPAL versus [vs.] AML/MDS), haploHCT approach (TCR alpha beta + T cell depletion vs. post-transplant cyclophosphamide [PTCy]); donor age (by ten-year increments), donor sex (maternal vs. paternal for parental donation), pre-HCT minimal residual disease status (MRD + vs MRD -); pediatric disease risk index (low, intermediate, and high, impact on OS and DFS only), conditioning regimen (chemotherapy based versus total-body irradiation [TBI] based), immunosuppressive regimen (anti-thymocyte globulin [ATG] exposure according to the weight and absolute lymphocyte count [ALC] dependent dosing approach vs no ATG exposure) time to transplant (interval between diagnosis/relapse and date of stem cell infusion) graft cell dose, use of relapse prevention therapy (yes or no) and weight on engraftment, OS, DFS, GRFS, relapse, transplant related mortality (TRM), aGvHD and cGvHD at 1 and 2 years after haplo and MUD HCT by performing stratified and multivariate analyses.

IV. To compare other important transplant related outcomes after haplo and MUD HCT, such as:

IVa. Incidence of any significant fungal infections (defined as proven or probable fungal infection) through 1 year post HCT; IVb. Incidence of viremia with or without end organ disease (i.e. cytomegalovirus [CMV], adenovirus, Epstein-Barr virus [EBV], human herpesvirus 6 [HHV-6], BK) requiring hospitalization and/or systemic antiviral therapy and/or cell therapy through 1 year post HCT; IVc. Incidence of sinusoidal obstruction syndrome (SOS) through 100 days post HCT; IVd. As defined by the Cairo criteria; IVe. To compare the incidence and outcome of SOS when different criteria are used (European Bone Marrow Transplant [EBMT], Cairo, Baltimore, and modified Seattle criteria); IVf. Incidence of transplant-associated thrombotic microangiopathy (TA-TMA) through 100 days post HCT.

  1. To compare immune recovery after haplo PTCy, haplo alpha-beta T cell depletion, and MUD HCT via:

Va. Pace of reconstitution of T, B, and natural killer (NK) cells and immunoglobulins at 30 days, 60 days, 100 days, 180 days and 365 days after HCT; Vb. Response to vaccinations as determined by vaccination-specific antibody titers at 12-18 months post hematopoietic stem cell transplant (HSCT); Vc. Biobanking blood or marrow to analyze the impact of graft composition on GvHD, relapse and viremia; Vd. Biobanking whole blood and serum to compare immune recovery using extended immune phenotyping and immune functional assessments.

VI. Biobanking whole blood or serum to measure rabbit antithymocyte globulin (rATG) exposure when dosed according to weight and absolute lymphocyte count (ALC) using established pharmacokinetic and pharmacodynamics assays (after last infusion, Day -4, Day 0, Day +7).

VII. To compare resource utilization after haplo and MUD HCT. VIIa. Length of HCT hospital stay from Day 0 and readmissions within the first 100 days (number of readmissions, duration, and reason).

VIIb. Inpatient costs within the first 100 days and at 2 years post HCT. VIII. To describe and compare outcomes (neutrophil and platelet engraftment, graft failure, OS, DFS, GRFS, NRM, relapse, GvHD and health-related quality of life [HRQOL] post HCT) by recipient race/ethnicity, annual household income, primary spoken language and conserved transcriptional response to adversity (CTRA).

IX. To describe HRQoL outcomes in racial/ethnic minorities and compare HRQoL outcomes between White patients receiving haploHCT and racial/ethnic minority patients receiving haploHCT.

  1. To assess the feasibility of incorporating total body irradiation (TBI) delivered with volumetric modulated arc therapy (VMAT) or tomotherapy into a multi-institutional study, to describe the toxicities and oncologic outcomes (relapse, DFS, OS, and TRM) of the subgroup of patients treated with this approach, and to compare these outcomes to those of patients treated with conventional TBI.

OUTLINE: Patients who have both a MUD and haplo donor are randomized to Arm A or Arm B. Patients who only have a haplo donor are nonrandomly assigned to Arm C.

ARM A: Patients receive a haplo HCT following a TBI- based or chemotherapy-based myeloablative conditioning regimen with PTCy or alpha beta T cell depletion (center's choice). When PTCy is used, it Is administered on days 3 and 4 after HCT and additional immunsouppression is started on day 5 after SCT.

ARM B: Patients receive a MUD HCT following a TBI-based or chemotherapy-based myeloablative conditioning regimen between days -9 and -2 Patients then receive GVHD prophylaxis on days 1-11.

ARM C: Patients receive a haploHCT following a TBI-based or chemotherapy-based myeloablative conditioning regimen with PTCy or alpha beta T cell depletion (center's choice). When PTCy is used, it Is administered on days 3 and 4 after HCT and additional immunsouppression is started on day 5 after SCT.

Patients in all arms undergo standard HCT screening prior to transplant including disease evaluation (lumbar puncture, bone marrow aspiration), and organ function evaluation including but not limited to echocardiogram (ECHO) or multigated acquisition scan (MUGA), PFTS, and bloodwork.Patients also undergo collection of blood throughout the trial.

After completion of study treatment, patients are followed periodically for up to 5 years from HCT.

Being tested
Biospecimen Collection, Bone Marrow Aspiration, Busulfan, Cyclophosphamide, Echocardiography Test
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Leukemia, Biphenotypic, Acute, Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo collection of blood

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow aspiration

  • BusulfanDrug

    Also called 1, 4-Bis[methanesulfonoxy]butane, BUS, Busilvex, Bussulfam

    Given intravenously (IV)

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518

    Given IV

  • Echocardiography TestProcedure or surgery

    Also called EC, Echocardiography

    Undergo ECHO

  • FludarabineDrug

    Also called Fluradosa

    Given IV

  • Haploidentical Hematopoietic Cell TransplantationProcedure or surgery

    Also called Haploidentical Stem Cell Transplantation, HLA-Haploidentical Hematopoietic Cell Transplantation, Stem Cell Transplantation, Haploidentical

    Undergo haploHCT

  • Lapine T-Lymphocyte Immune GlobulinBiological

    Also called Anti-Thymocyte Globulin Rabbit, Antithymocyte Globulin Rabbit, Antithymocyte globulin rabbit ATG, Grafalon

    Given IV

  • Lumbar PunctureProcedure or surgery

    Also called LP, Spinal Tap

    Undergo lumbar puncture

  • Matched Unrelated Donor Hematopoietic Cell TransplantationProcedure or surgery

    Also called MUD-HCT

    Undergo MUD-HCT

  • MelphalanDrug

    Also called Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard

    Given IV

  • MethotrexateDrug

    Also called Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate

    Given IV

  • Multigated Acquisition ScanProcedure or surgery

    Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan

    Undergo MUGA

  • Mycophenolate MofetilDrug

    Also called CellCept, MMF, Myhibbin

    Given IV

  • Myeloablative ConditioningProcedure or surgery

    Also called Myeloablation, Myeloablative, Myeloablative Cytoreduction

    Receive myeloablative conditioning regimen

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

  • RituximabBiological

    Also called ABP 798, ABP-798, ABP798, BI 695500

    Given IV

  • T-Cell Depletion TherapyProcedure or surgery

    Also called T-Cell Depletion, T-Lymphocyte Depletion Therapy

    Undergo haploHCT with alpha beta T cell depletion

  • TacrolimusDrug

    Also called FK 506, FK-506, FK506, Fujimycin

    Given IV

  • ThiotepaDrug

    Also called 1,1',1''-Phosphinothioylidynetrisaziridine, Girostan, N,N', N''-Triethylenethiophosphoramide, Oncotiotepa

    Given IV

  • Total-Body IrradiationRadiation

    Also called SCT_TBI, TBI, Total Body Irradiation, Whole Body

    Undergo TBI

Study groups in NCT05457556
Study groupRoleWhat they receive
Arm A (halploHCT)ExperimentalPatients 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.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Drug: Busulfan; Drug: Cyclophosphamide; Procedure: Echocardiography Test; Drug: Fludarabine; Procedure: Haploidentical Hematopoietic Cell Transplantation; Biological: Lapine T-Lymphocyte Immune Globulin; Procedure: Lumbar Puncture; Drug: Melphalan; Procedure: Multigated Acquisition Scan; Drug: Mycophenolate Mofetil; Procedure: Myeloablative Conditioning; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Biological: Rituximab; Procedure: T-Cell Depletion Therapy; Drug: Tacrolimus; Drug: Thiotepa; Radiation: Total-Body Irradiation
Arm B (MUD-HCT)ExperimentalPatients 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.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Drug: Busulfan; Drug: Cyclophosphamide; Procedure: Echocardiography Test; Drug: Fludarabine; Biological: Lapine T-Lymphocyte Immune Globulin; Procedure: Lumbar Puncture; Procedure: Matched Unrelated Donor Hematopoietic Cell Transplantation; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Procedure: Myeloablative Conditioning; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Tacrolimus; Drug: Thiotepa; Radiation: Total-Body Irradiation
Arm C (haploHCT)ExperimentalPatients 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.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Drug: Busulfan; Drug: Cyclophosphamide; Procedure: Echocardiography Test; Drug: Fludarabine; Procedure: Haploidentical Hematopoietic Cell Transplantation; Biological: Lapine T-Lymphocyte Immune Globulin; Procedure: Lumbar Puncture; Drug: Melphalan; Procedure: Multigated Acquisition Scan; Drug: Mycophenolate Mofetil; Procedure: Myeloablative Conditioning; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Biological: Rituximab; Procedure: T-Cell Depletion Therapy; Drug: Tacrolimus; Drug: Thiotepa; Radiation: Total-Body Irradiation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Severe GVHD (Grade III-IV acute GVHD or chronic GVHD requiring systemic immunosuppressive therapy)

    We will estimate the cumulative incidence of severe GVHD at 1-year post-HCT and corresponding 95% confidence interval among enrolled and eligible patients randomly assigned to either HAPLO or MUD arms who actually undergo HCT.

    Measured: Up-to 1-year post hematopoietic cell transplantation (HCT)

  2. Disease free survival (DFS) (where an event is the occurrence of death from any cause or relapse)

    We will estimate the cumulative incidence at 1 year post randomization and the corresponding 95% confidence interval among all enrolled and eligible patients randomly assigned to either HAPLO or MUD arms.

    Measured: From date of randomization to up-to 1 year post randomization

Secondary outcomes (3)

  1. Overall survival (OS)

    We will estimate the cumulative incidence of all-cause mortality events up-to 1-year post-HCT and the corresponding 95% confidence interval among all enrolled, eligible, randomized patients.

    Measured: From date of randomization to up-to 1-year post-HCT

  2. Summary score from the Generic Pediatric Quality of Life Inventory (PedsQL) (excluding School Functioning)

    For enrolled, eligible patients who consent to optional QoL studies, we will estimate the mean PedsQL score (excluding School Functioning) among patients randomized to the Haplo arm, the MUD arm, and among patients who enroll to arm C. For each, we will also calculate a corresponding 95% confidence interval.

    Measured: At 6-months, 1 year and 2 years post-HCT

  3. Summary score from the PedsQL Stem Cell Transplant module

    For enrolled, eligible patients who consent to optional QoL studies, we will estimate the mean PedsQL Stem Cell Transplant module score among patients randomized to the Haplo arm and the MUD arm, and among patients who enroll to arm C. For each, we will calculate a corresponding 95% confidence interval.

    Measured: 6-months, 1 year and 2 years post-HCT

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jul 2022
  2. Study start15 Mar 2023
  3. Primary completion30 Jun 2026
  4. Study completion7 Jul 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
66 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05457556
Sponsor's protocol ID
ASCT2031
Other IDs
NCI-2022-07080, ASCT2031, ASCT2031, U10CA180886
Status last verified
Jul 2026
First submitted
11 Jul 2022
Last updated
30 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Biospecimen Collection, Bone Marrow Aspiration and Busulfan in people with Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia, run by Children's Oncology Group at 63 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 76 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 30 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 63 sites in United States, Canada, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the 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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05457556.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2026.

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Clinical Trial NCT05457556 | AzTrials