MT2021-08T Cell Receptor Alpha/Beta Depletion PBSC Transplantation for Heme Malignancies

Phase 2

Recruiting

• Conditions: Hematologic Malignancy; Minimal Residual Disease; PTPN11 Gene Mutation; Monosomy 7; Chromosome Abnormality; Acute Leukemia; Remission; TP53; Intrachromosomal Amplification of Chromosome 21; Myelodysplasia
• Interventions: Drug: Fludarabine; Drug: Rituximab; Drug: Busulfan; Drug: Levetiracetam; Drug: Melphalan; Biological: Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells; Drug: Thymoglobulin; Drug: Cyclophosphamide

• Registration Number: NCT05735717
• Lead Sponsor: Masonic Cancer Center, University of Minnesota

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-01-10
• Study First Submitted QC: 2023-02-09
• Study First Posted: 2023-02-21
• Study Start: 2023-05-11
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-21
• Last Update Posted: 2025-07-24
• Primary Completion: 2027-11-30
• Study Completion: 2030-11-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 70

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1A: Fludarabine (flu), Total Body Irradiation (TBI), Flu/TBI Regimen, Closed to Accrual	Fludarabine	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.
Arm 1A: Fludarabine (flu), Total Body Irradiation (TBI), Flu/TBI Regimen, Closed to Accrual	Rituximab	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.
Arm 1A: Fludarabine (flu), Total Body Irradiation (TBI), Flu/TBI Regimen, Closed to Accrual	Levetiracetam	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.
Arm 1A: Fludarabine (flu), Total Body Irradiation (TBI), Flu/TBI Regimen, Closed to Accrual	Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells	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.
Arm 2A: Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen, Closed to Accrual	Fludarabine	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.
Arm 2A: Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen, Closed to Accrual	Busulfan	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.
Arm 2A: Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen, Closed to Accrual	Rituximab	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.
Arm 2A: Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen, Closed to Accrual	Levetiracetam	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.
Arm 3A: Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only	Fludarabine	Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia. , Closed to Accrual
Arm 3A: Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only	Busulfan	Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia. , Closed to Accrual
Arm 3A: Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only	Melphalan	Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia. , Closed to Accrual
Arm 3A: Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only	Rituximab	Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia. , Closed to Accrual
Arm 3A: Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only	Levetiracetam	Flu/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	Fludarabine	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.
Arm 1B: ATG, Fludarabine (flu), Total Body Irradiation (TBI), Flu/TBI Regimen	Rituximab	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.
Arm 1B: ATG, Fludarabine (flu), Total Body Irradiation (TBI), Flu/TBI Regimen	Levetiracetam	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.
Arm 1B: ATG, Fludarabine (flu), Total Body Irradiation (TBI), Flu/TBI Regimen	Thymoglobulin	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.
Arm 2B: ATG, Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen	Fludarabine	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.
Arm 2B: ATG, Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen	Busulfan	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.
Arm 2B: ATG, Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen	Rituximab	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.
Arm 2B: ATG, Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen	Levetiracetam	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.
Arm 2B: ATG, Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen	Thymoglobulin	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.
Arm 3B: ATG, Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only	Fludarabine	ATG/Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia.
Arm 3B: ATG, Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only	Busulfan	ATG/Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia.
Arm 3B: ATG, Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only	Melphalan	ATG/Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia.
Arm 3B: ATG, Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only	Rituximab	ATG/Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia.
Arm 3B: ATG, Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only	Levetiracetam	ATG/Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia.
Arm 3B: ATG, Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only	Thymoglobulin	ATG/Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia.
Arm 4B: ATG, Busulfan (BU), Cyclophosphamide (CY)	Busulfan	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.
Arm 4B: ATG, Busulfan (BU), Cyclophosphamide (CY)	Rituximab	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.
Arm 4B: ATG, Busulfan (BU), Cyclophosphamide (CY)	Levetiracetam	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.
Arm 4B: ATG, Busulfan (BU), Cyclophosphamide (CY)	Thymoglobulin	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.
Arm 4B: ATG, Busulfan (BU), Cyclophosphamide (CY)	Cyclophosphamide	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.
Arm 5B: ATG, Cyclophosphamide (CY), Total Body Irradiation (TBI)	Rituximab	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.
Arm 5B: ATG, Cyclophosphamide (CY), Total Body Irradiation (TBI)	Levetiracetam	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.
Arm 5B: ATG, Cyclophosphamide (CY), Total Body Irradiation (TBI)	Thymoglobulin	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.
Arm 5B: ATG, Cyclophosphamide (CY), Total Body Irradiation (TBI)	Cyclophosphamide	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.

Primary Outcome Measures

Name	Time	Method
Determine the rate of GVHD after alpha beta TCR depletion	100 days	GVHD incidence after treatment.

Secondary Outcome Measures

Name	Time	Method
Non-relapse mortality (NRM)	12 months	Determine the incidence of non-relapse mortality (NRM) at 100 days and 1 year
Transplant engraftment	42 days	Monitor median rate of engraftment by 42 days.
Overall survival (OS)	12 months	Number of participants experiencing progression free survival at one year follow up
Graft Failure	100 days	Determine the rate of graft failure by day 100 (defined as lack of achievement of an ANC \>=500/mL with associated pancytopenia)

Trial Locations

Locations (1)

University of Minnesota Masonic Cancer Center; 🇺🇸 Minneapolis, Minnesota, United States