Mismatched Related Donor Versus Matched Unrelated Donor Stem Cell Transplantation for Children, Adolescents, and Young Adults With Acute Leukemia or Myelodysplastic Syndrome
NCT ID: NCT05457556
Last Updated: 2025-12-22
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
ACTIVE_NOT_RECRUITING
Clinical Phase
PHASE3
Total Enrollment
435 participants
Study Classification
INTERVENTIONAL
Study Start Date
2023-03-15
Study Completion Date
2026-06-30
Brief Summary
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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.
Detailed Description
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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), 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:
I. 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:
I. 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.
V. 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.
X. 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.
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), 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:
I. 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:
I. 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.
V. 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.
X. 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.
Conditions
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Acute Lymphoblastic Leukemia
Acute Myeloid Leukemia
Mixed Phenotype Acute Leukemia
Myelodysplastic Syndrome
Study Design
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Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
Primary Study Purpose
TREATMENT
Blinding Strategy
NONE
Study Groups
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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.
Group Type
EXPERIMENTAL
Biospecimen Collection
Intervention Type
PROCEDURE
Undergo collection of blood
Bone Marrow Aspiration
Intervention Type
PROCEDURE
Undergo bone marrow aspiration
Busulfan
Intervention Type
DRUG
Given intravenously (IV)
Cyclophosphamide
Intervention Type
DRUG
Given IV
Echocardiography Test
Intervention Type
PROCEDURE
Undergo ECHO
Fludarabine
Intervention Type
DRUG
Given IV
Haploidentical Hematopoietic Cell Transplantation
Intervention Type
PROCEDURE
Undergo haploHCT
Lapine T-Lymphocyte Immune Globulin
Intervention Type
BIOLOGICAL
Given IV
Lumbar Puncture
Intervention Type
PROCEDURE
Undergo lumbar puncture
Melphalan
Intervention Type
DRUG
Given IV
Multigated Acquisition Scan
Intervention Type
PROCEDURE
Undergo MUGA
Mycophenolate Mofetil
Intervention Type
DRUG
Given IV
Myeloablative Conditioning
Intervention Type
PROCEDURE
Receive myeloablative conditioning regimen
Quality-of-Life Assessment
Intervention Type
OTHER
Ancillary studies
Questionnaire Administration
Intervention Type
OTHER
Ancillary studies
Rituximab
Intervention Type
BIOLOGICAL
Given IV
T-Cell Depletion Therapy
Intervention Type
PROCEDURE
Undergo haploHCT with alpha beta T cell depletion
Tacrolimus
Intervention Type
DRUG
Given IV
Thiotepa
Intervention Type
DRUG
Given IV
Total-Body Irradiation
Intervention Type
RADIATION
Undergo TBI
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.
Group Type
EXPERIMENTAL
Biospecimen Collection
Intervention Type
PROCEDURE
Undergo collection of blood
Bone Marrow Aspiration
Intervention Type
PROCEDURE
Undergo bone marrow aspiration
Busulfan
Intervention Type
DRUG
Given intravenously (IV)
Cyclophosphamide
Intervention Type
DRUG
Given IV
Echocardiography Test
Intervention Type
PROCEDURE
Undergo ECHO
Fludarabine
Intervention Type
DRUG
Given IV
Lapine T-Lymphocyte Immune Globulin
Intervention Type
BIOLOGICAL
Given IV
Lumbar Puncture
Intervention Type
PROCEDURE
Undergo lumbar puncture
Matched Unrelated Donor Hematopoietic Cell Transplantation
Intervention Type
PROCEDURE
Undergo MUD-HCT
Methotrexate
Intervention Type
DRUG
Given IV
Multigated Acquisition Scan
Intervention Type
PROCEDURE
Undergo MUGA
Myeloablative Conditioning
Intervention Type
PROCEDURE
Receive myeloablative conditioning regimen
Quality-of-Life Assessment
Intervention Type
OTHER
Ancillary studies
Questionnaire Administration
Intervention Type
OTHER
Ancillary studies
Tacrolimus
Intervention Type
DRUG
Given IV
Thiotepa
Intervention Type
DRUG
Given IV
Total-Body Irradiation
Intervention Type
RADIATION
Undergo TBI
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.
Group Type
EXPERIMENTAL
Biospecimen Collection
Intervention Type
PROCEDURE
Undergo collection of blood
Bone Marrow Aspiration
Intervention Type
PROCEDURE
Undergo bone marrow aspiration
Busulfan
Intervention Type
DRUG
Given intravenously (IV)
Cyclophosphamide
Intervention Type
DRUG
Given IV
Echocardiography Test
Intervention Type
PROCEDURE
Undergo ECHO
Fludarabine
Intervention Type
DRUG
Given IV
Haploidentical Hematopoietic Cell Transplantation
Intervention Type
PROCEDURE
Undergo haploHCT
Lapine T-Lymphocyte Immune Globulin
Intervention Type
BIOLOGICAL
Given IV
Lumbar Puncture
Intervention Type
PROCEDURE
Undergo lumbar puncture
Melphalan
Intervention Type
DRUG
Given IV
Multigated Acquisition Scan
Intervention Type
PROCEDURE
Undergo MUGA
Mycophenolate Mofetil
Intervention Type
DRUG
Given IV
Myeloablative Conditioning
Intervention Type
PROCEDURE
Receive myeloablative conditioning regimen
Quality-of-Life Assessment
Intervention Type
OTHER
Ancillary studies
Questionnaire Administration
Intervention Type
OTHER
Ancillary studies
Rituximab
Intervention Type
BIOLOGICAL
Given IV
T-Cell Depletion Therapy
Intervention Type
PROCEDURE
Undergo haploHCT with alpha beta T cell depletion
Tacrolimus
Intervention Type
DRUG
Given IV
Thiotepa
Intervention Type
DRUG
Given IV
Total-Body Irradiation
Intervention Type
RADIATION
Undergo TBI
Interventions
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Biospecimen Collection
Undergo collection of blood
Intervention Type
PROCEDURE
Bone Marrow Aspiration
Undergo bone marrow aspiration
Intervention Type
PROCEDURE
Busulfan
Given intravenously (IV)
Intervention Type
DRUG
Cyclophosphamide
Given IV
Intervention Type
DRUG
Echocardiography Test
Undergo ECHO
Intervention Type
PROCEDURE
Fludarabine
Given IV
Intervention Type
DRUG
Haploidentical Hematopoietic Cell Transplantation
Undergo haploHCT
Intervention Type
PROCEDURE
Lapine T-Lymphocyte Immune Globulin
Given IV
Intervention Type
BIOLOGICAL
Lumbar Puncture
Undergo lumbar puncture
Intervention Type
PROCEDURE
Matched Unrelated Donor Hematopoietic Cell Transplantation
Undergo MUD-HCT
Intervention Type
PROCEDURE
Melphalan
Given IV
Intervention Type
DRUG
Methotrexate
Given IV
Intervention Type
DRUG
Multigated Acquisition Scan
Undergo MUGA
Intervention Type
PROCEDURE
Mycophenolate Mofetil
Given IV
Intervention Type
DRUG
Myeloablative Conditioning
Receive myeloablative conditioning regimen
Intervention Type
PROCEDURE
Quality-of-Life Assessment
Ancillary studies
Intervention Type
OTHER
Questionnaire Administration
Ancillary studies
Intervention Type
OTHER
Rituximab
Given IV
Intervention Type
BIOLOGICAL
T-Cell Depletion Therapy
Undergo haploHCT with alpha beta T cell depletion
Intervention Type
PROCEDURE
Tacrolimus
Given IV
Intervention Type
DRUG
Thiotepa
Given IV
Intervention Type
DRUG
Total-Body Irradiation
Undergo TBI
Intervention Type
RADIATION
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Biological Sample Collection
Biospecimen Collected
Specimen Collection
1, 4-Bis[methanesulfonoxy]butane
BUS
Busilvex
Bussulfam
Busulfanum
Busulfex
Busulphan
CB 2041
CB-2041
Glyzophrol
GT 41
GT-41
Joacamine
Methanesulfonic Acid Tetramethylene Ester
Methanesulfonic acid, tetramethylene ester
Mielucin
Misulban
Misulfan
Mitosan
Myeleukon
Myeloleukon
Myelosan
Mylecytan
Myleran
Sulfabutin
Tetramethylene Bis(methanesulfonate)
Tetramethylene bis[methanesulfonate]
WR-19508
(-)-Cyclophosphamide
2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
Asta B 518
B 518
B-518
B518
Carloxan
Ciclofosfamida
Ciclofosfamide
Cicloxal
Clafen
Claphene
CP monohydrate
CTX
CYCLO-cell
Cycloblastin
Cycloblastine
Cyclophospham
Cyclophosphamid monohydrate
Cyclophosphamide Monohydrate
Cyclophosphamidum
Cyclophosphan
Cyclophosphane
Cyclophosphanum
Cyclostin
Cyclostine
Cytophosphan
Cytophosphane
Cytoxan
Fosfaseron
Genoxal
Genuxal
Ledoxina
Mitoxan
Neosar
Revimmune
Syklofosfamid
WR 138719
WR- 138719
WR-138719
WR138719
EC
Echocardiography
Fluradosa
Haploidentical Stem Cell Transplantation
HLA-Haploidentical Hematopoietic Cell Transplantation
Stem Cell Transplantation, Haploidentical
Anti-Thymocyte Globulin Rabbit
Antithymocyte Globulin Rabbit
Antithymocyte globulin rabbit ATG
Grafalon
Imtix
Rabbit Anti-Human Thymocyte Globulin (RATG)
Rabbit Anti-Thymocyte Globulin
Rabbit Antithymocyte Globulin
Rabbit ATG
Thymoglobulin
LP
Spinal Tap
MUD-HCT
Alanine Nitrogen Mustard
CB-3025
L-PAM
L-Phenylalanine Mustard
L-Sarcolysin
L-Sarcolysin Phenylalanine mustard
L-Sarcolysine
Melphalan for Injection-Hepatic Delivery System
Melphalanum
Phenylalanine Mustard
Phenylalanine Nitrogen Mustard
Sarcoclorin
Sarkolysin
WR-19813
Abitrexate
Alpha-Methopterin
Amethopterin
Brimexate
CL 14377
CL-14377
Emtexate
Emthexat
Emthexate
Farmitrexat
Fauldexato
Folex
Folex PFS
Jylamvo
Lantarel
Ledertrexate
Lumexon
Maxtrex
Medsatrexate
Metex
Methoblastin
Methotrexate LPF
Methotrexate Methylaminopterin
Methotrexatum
Metotrexato
Metrotex
Mexate
Mexate-AQ
MTX
Novatrex
Rheumatrex
Texate
Tremetex
Trexeron
Trixilem
WR-19039
Blood Pool Scan
Equilibrium Radionuclide Angiography
Gated Blood Pool Imaging
Gated Heart Pool Scan
MUGA
MUGA Scan
Multi-Gated Acquisition Scan
Radionuclide Ventriculogram Scan
Radionuclide Ventriculography
RNV Scan
RNVG
SYMA Scanning
Synchronized Multigated Acquisition Scanning
CellCept
MMF
Myeloablation
Myeloablative
Myeloablative Cytoreduction
Quality of Life Assessment
ABP 798
ABP-798
ABP798
BI 695500
BI-695500
BI695500
Blitzima
C2B8 Monoclonal Antibody
Chimeric Anti-CD20 Antibody
CT P10
CT-P10
CTP10
GP 2013
GP-2013
GP2013
IDEC 102
IDEC-102
IDEC-C2B8
IDEC-C2B8 Monoclonal Antibody
IDEC102
Ikgdar
Mabtas
MabThera
Monoclonal Antibody IDEC-C2B8
PF 05280586
PF-05280586
PF05280586
Riabni
Ritemvia
Rituxan
Rituximab ABBS
Rituximab ARRX
Rituximab Biosimilar ABP 798
Rituximab Biosimilar BI 695500
Rituximab Biosimilar CT-P10
Rituximab Biosimilar GB241
Rituximab Biosimilar GP2013
Rituximab Biosimilar IBI301
Rituximab Biosimilar JHL1101
Rituximab Biosimilar PF-05280586
Rituximab Biosimilar RTXM83
Rituximab Biosimilar SAIT101
Rituximab Biosimilar SIBP-02
rituximab biosimilar TQB2303
Rituximab PVVR
Rituximab-abbs
Rituximab-arrx
Rituximab-blit
Rituximab-pvvr
Rituximab-rite
Rituximab-rixa
Rituximab-rixi
Rixathon
Riximyo
RTXM 83
RTXM-83
RTXM83
Ruxience
Truxima
T-Cell Depletion
T-Lymphocyte Depletion Therapy
FK 506
FK-506
FK506
Fujimycin
Hecoria
Prograf
Protopic
Tacforius
1,1',1''-Phosphinothioylidynetrisaziridine
Girostan
N,N', N''-Triethylenethiophosphoramide
Oncotiotepa
SH 105
SH-105
SH105
STEPA
Tepadina
Tepylute
TESPA
Tespamin
Tespamine
Thio-Tepa
Thiofosfamide
Thiofozil
Thiophosphamide
Thiophosphoamide
Thiophosphoramide
Thiotef
Tifosyl
TIO TEF
Tio-tef
Triethylene Thiophosphoramide
Triethylenethiophosphoramide
Tris(1-aziridinyl)phosphine sulfide
TSPA
WR 45312
SCT_TBI
TBI
Total Body Irradiation
Whole Body
Whole Body Irradiation
Whole-Body Irradiation
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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
* 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)
1. to \< 2 years: 0.6 mg/dL (Male); 0.6 mg/dL (Female)
2. 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
* 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
* 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)
1. to \< 2 years: 0.6 mg/dL (Male); 0.6 mg/dL (Female)
2. 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
Exclusion Criteria
* 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
* 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
* 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
* 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
Minimum Eligible Age
6 Months
Maximum Eligible Age
21 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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Children's Oncology Group
NETWORK
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Principal Investigators
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Heather J Symons
Role: PRINCIPAL_INVESTIGATOR
Children's Oncology Group
Locations
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Children's Hospital of Alabama
Birmingham, Alabama, United States
Site Status
Phoenix Childrens Hospital
Phoenix, Arizona, United States
Site Status
Arkansas Children's Hospital
Little Rock, Arkansas, United States
Site Status
City of Hope Comprehensive Cancer Center
Duarte, California, United States
Site Status
Loma Linda University Medical Center
Loma Linda, California, United States
Site Status
Children's Hospital Los Angeles
Los Angeles, California, United States
Site Status
UCSF Benioff Children's Hospital Oakland
Oakland, California, United States
Site Status
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, United States
Site Status
UCSF Medical Center-Mission Bay
San Francisco, California, United States
Site Status
Children's Hospital Colorado
Aurora, Colorado, United States
Site Status
Yale University
New Haven, Connecticut, United States
Site Status
Alfred I duPont Hospital for Children
Wilmington, Delaware, United States
Site Status
Children's National Medical Center
Washington D.C., District of Columbia, United States
Site Status
UF Health Cancer Institute - Gainesville
Gainesville, Florida, United States
Site Status
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, United States
Site Status
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States
Site Status
Nicklaus Children's Hospital
Miami, Florida, United States
Site Status
AdventHealth Orlando
Orlando, Florida, United States
Site Status
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, United States
Site Status
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States
Site Status
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Site Status
Riley Hospital for Children
Indianapolis, Indiana, United States
Site Status
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, United States
Site Status
Norton Children's Hospital
Louisville, Kentucky, United States
Site Status
Children's Hospital New Orleans
New Orleans, Louisiana, United States
Site Status
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
Site Status
C S Mott Children's Hospital
Ann Arbor, Michigan, United States
Site Status
Children's Hospital of Michigan
Detroit, Michigan, United States
Site Status
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, United States
Site Status
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Site Status
University of Mississippi Medical Center
Jackson, Mississippi, United States
Site Status
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, United States
Site Status
Washington University School of Medicine
St Louis, Missouri, United States
Site Status
Hackensack University Medical Center
Hackensack, New Jersey, United States
Site Status
Roswell Park Cancer Institute
Buffalo, New York, United States
Site Status
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York, United States
Site Status
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, United States
Site Status
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, United States
Site Status
University of Rochester
Rochester, New York, United States
Site Status
Montefiore Medical Center - Moses Campus
The Bronx, New York, United States
Site Status
New York Medical College
Valhalla, New York, United States
Site Status
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, United States
Site Status
Duke University Medical Center
Durham, North Carolina, United States
Site Status
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Site Status
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
Site Status
Penn State Children's Hospital
Hershey, Pennsylvania, United States
Site Status
Medical University of South Carolina
Charleston, South Carolina, United States
Site Status
The Children's Hospital at TriStar Centennial
Nashville, Tennessee, United States
Site Status
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States
Site Status
Medical City Dallas Hospital
Dallas, Texas, United States
Site Status
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, United States
Site Status
Cook Children's Medical Center
Fort Worth, Texas, United States
Site Status
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, United States
Site Status
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States
Site Status
Primary Children's Hospital
Salt Lake City, Utah, United States
Site Status
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, United States
Site Status
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, United States
Site Status
The Children's Hospital at Westmead
Westmead, New South Wales, Australia
Site Status
Alberta Children's Hospital
Calgary, Alberta, Canada
Site Status
British Columbia Children's Hospital
Vancouver, British Columbia, Canada
Site Status
CancerCare Manitoba
Winnipeg, Manitoba, Canada
Site Status
Hospital for Sick Children
Toronto, Ontario, Canada
Site Status
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, Canada
Site Status
Countries
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United States
Australia
Canada
Other Identifiers
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ASCT2031
Identifier Type: -
Identifier Source: org_study_id
NCI-2022-07080
Identifier Type: REGISTRY
Identifier Source: secondary_id
ASCT2031
Identifier Type: OTHER
Identifier Source: secondary_id
ASCT2031
Identifier Type: OTHER
Identifier Source: secondary_id