Recruiting
Phase 2

MT2021-08 TCR Depletion

Sponsor:

Masonic Cancer Center, University of Minnesota

Code:

NCT05735717

Conditions

Hematologic Malignancy

Acute Leukemia

Remission

Acute Myeloid Leukemia

Acute Lymphoblastic Leukemia

Eligibility Criteria

Sex: All

Age: 0 - 60

Healthy Volunteers: Not accepted

Interventions

Fludarabine

Busulfan

Melphalan

Rituximab

Levetiracetam

Study Details

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.

Conditions

Hematologic Malignancy

Acute Leukemia

Remission

Acute Myeloid Leukemia

Acute Lymphoblastic Leukemia

Study ID

NCT05735717

Start date

May 11, 2023

Status verified date

Mar, 2026

Completion date

Nov 30, 2030

Anticipated

Primary completion date

Nov 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0 - 60

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Design

Enrollment

70 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm 1A: Fludarabine (flu), Total Body Irradiation (TBI), Flu/TBI Regimen, Closed to Accrual

Patients 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.

experimental: Arm 2A: Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen, Closed to Accrual

Patients 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.

experimental: Arm 3A: Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only

Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia. , Closed to Accrual

experimental: Arm 1B: ATG, Fludarabine (flu), Total Body Irradiation (TBI), Flu/TBI Regimen

Patients 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.

experimental: Arm 2B: ATG, Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen

Patients 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.

experimental: Arm 3B: ATG, Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only

ATG/Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia.

experimental: Arm 4B: ATG, Busulfan (BU), Cyclophosphamide (CY)

Patients 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.

experimental: Arm 5B: ATG, Cyclophosphamide (CY), Total Body Irradiation (TBI)

Patients 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

Fludarabine 25mg/m2 IV on days -8 to -6 or days -4 to -2. 40mg/m2 IV on days -5 to -2.

Busulfan

Busulfan 82.1 mg\*hr/L IV on days -5 to -2 or days -8 to -5

Melphalan

Melphalan 50 mg/m2 IV on days -4 to -2

Rituximab

200 mg/m2 intravenous given once on day-1

Levetiracetam

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.

Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells

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.

Thymoglobulin

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

Cyclophosphamide 60 mg/kg IV over 2 hours on days -3 and -2

Primary outcome measure

  • Determine the rate of GVHD after alpha beta TCR depletion [ Time Frame: 100 days ]

Central Contacts and Locations

Central contacts

Margaret MacMillan

612-626-2961macmi002@umn.edu

Locations

University of Minnesota Masonic Cancer Center

Recruiting

Minneapolis, Minnesota, United States, 55455

More Information

Sponsor

Masonic Cancer Center, University of Minnesota

Last update posted

Apr 6, 2026

Last verified

Mar, 2026

Keywords

  • Bu
  • Flu
  • G-CSF
  • GFSR
  • aGVHD
  • HCT
  • MAC
  • Mel
  • PBSCT
  • PTLD
  • RECIST
  • TCR

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-06. This information was provided to ClinicalTrials.gov by Masonic Cancer Center, University of Minnesota on 2026-04-06.