MT2021-08T Cell Receptor Alpha/Beta Depletion PBSC Transplantation for Heme Malignancies
Phase II, Open-Label, Prospective Study of T Cell Receptor Alpha/Beta Depletion (A/B TCD) Peripheral Blood Stem Cell (PBSC) Transplantation for Children and Adults With Hematological Malignancies
1 other identifier
interventional
70
1 country
1
Brief Summary
This is a phase II, open-label, prospective study of T cell receptor alpha/beta depletion (TCR α/β TCD) peripheral blood stem cell (PBSC) transplantation for children and adults with hematological malignancies. This is a safety/feasibility study of the investigational procedure/product.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started May 2023
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 10, 2023
CompletedFirst Posted
Study publicly available on registry
February 21, 2023
CompletedStudy Start
First participant enrolled
May 11, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 30, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
November 30, 2030
July 24, 2025
July 1, 2025
4.6 years
January 10, 2023
July 21, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Determine the rate of GVHD after alpha beta TCR depletion
GVHD incidence after treatment.
100 days
Secondary Outcomes (4)
Transplant engraftment
42 days
Graft Failure
100 days
Non-relapse mortality (NRM)
12 months
Overall survival (OS)
12 months
Study Arms (8)
Arm 1A: Fludarabine (flu), Total Body Irradiation (TBI), Flu/TBI Regimen, Closed to Accrual
EXPERIMENTALPatients will be treated on the most medically appropriate regimen with a preference for Flu/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
Arm 2A: Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen, Closed to Accrual
EXPERIMENTALPatients will be treated on the most medically appropriate regimen with a preference for Flu/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
Arm 3A: Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only
EXPERIMENTALFlu/Bu/Mel will the preference for patients with JMML or infants with leukemia. , Closed to Accrual
Arm 1B: ATG, Fludarabine (flu), Total Body Irradiation (TBI), Flu/TBI Regimen
EXPERIMENTALPatients will be treated on the most medically appropriate regimen with a preference for ATG/Flu/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
Arm 2B: ATG, Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen
EXPERIMENTALPatients will be treated on the most medically appropriate regimen with a preference for ATG/Flu/BU/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
Arm 3B: ATG, Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only
EXPERIMENTALATG/Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia.
Arm 4B: ATG, Busulfan (BU), Cyclophosphamide (CY)
EXPERIMENTALPatients will be treated on the most medically appropriate regimen with a preference for ATG/BU/CY Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
Arm 5B: ATG, Cyclophosphamide (CY), Total Body Irradiation (TBI)
EXPERIMENTALPatients will be treated on the most medically appropriate regimen with a preference for ATG/CY/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
Interventions
Fludarabine 25mg/m2 IV on days -8 to -6 or days -4 to -2. 40mg/m2 IV on days -5 to -2.
Busulfan 82.1 mg\*hr/L IV on days -5 to -2 or days -8 to -5
Melphalan 50 mg/m2 IV on days -4 to -2
200 mg/m2 intravenous given once on day-1
As seizures have occurred following high dose busulfan, all patients will be treated with Keppra beginning day -6 and continuing until day -1 per institutional guidelines.
Patients will be treated on the most medically appropriate regimen followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
rabbit anti-thymocyte globulin (rATG). Used in conditioning regimens for in vivo depletion of T cells, and the use of fludarabine model-based dosing to optimize dosing.
Cyclophosphamide 60 mg/kg IV over 2 hours on days -3 and -2
Eligibility Criteria
You may qualify if:
- Histological confirmation of hematological malignancies
- Acute leukemias
- Acute Myeloid Leukemia (AML) and related precursor neoplasms
- Favorable risk AML is defined as having one of the following:
- Acute lymphoblastic leukemia (ALL)/lymphoma
- Myelodysplasia (MDS) IPSS INT-2 or High Risk (i.e. RAEB, RAEBt) or Refractory Anemia with severe pancytopenia, transfusion dependence, or high risk cytogenetics or molecular features.
- Age 60 years of age or younger at the time of consent
- Karnofsky performance status ≥ 70% or Lansky play score 50% for ≤16 years of age.
- Adequate organ function
You may not qualify if:
- Pregnant or breastfeeding.
- Active uncontrolled infection within 1 week of starting preparative therapy
- Known seropositive for HIV or known active Hepatitis B or C infection with detectable viral load by PCR.
- Any prior autologous or allogeneic transplant
- CML blast crisis
- Active central nervous system malignancy
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Minnesota Masonic Cancer Center
Minneapolis, Minnesota, 55455, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Margaret MacMillan
University of Minnesota Masonic Cancer Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 10, 2023
First Posted
February 21, 2023
Study Start
May 11, 2023
Primary Completion (Estimated)
November 30, 2027
Study Completion (Estimated)
November 30, 2030
Last Updated
July 24, 2025
Record last verified: 2025-07
Data Sharing
- IPD Sharing
- Will not share
For the purposes of data and safety monitoring, this study is classified as high risk (investigator initiated under an IND). Therefore the following requirements will be fulfilled: * The Masonic Cancer Center Data and Safety Monitoring Council (DSMC) will review the study's progress at least quarterly. * The PI will comply with at least twice yearly monitoring of the project by the Masonic Cancer Center monitoring services. * The PI will oversee the submission of all reportable adverse events per the definition of reportable in Section 11.5 to the Masonic Cancer Center's SAE Coordinator, the University of Minnesota IRB, and the FDA.