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

NCT ID: NCT05735717

Last Updated: 2025-07-24

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

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-05-11

Study Completion Date

2030-11-30

Brief Summary

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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

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Conditions

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Hematologic Malignancy Acute Leukemia Remission Acute Myeloid Leukemia Acute Lymphoblastic Leukemia AML TP53 Intrachromosomal Amplification of Chromosome 21 Cytogenetic Abnormality CNS Leukemia Minimal Residual Disease Myelodysplasia Juvenile Myelomonocytic Leukemia Somatic Mutation PTPN11 Gene Mutation N-RAS Gene Amplification Neurofibromatosis 1 NF1 Mutation CBL Gene Mutation Monosomy 7 Chromosome Abnormality Fetal Hemoglobin

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Fludarabine

Intervention Type DRUG

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

Rituximab

Intervention Type DRUG

200 mg/m2 intravenous given once on day-1

Levetiracetam

Intervention Type DRUG

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

Intervention Type BIOLOGICAL

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.

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.

Group Type EXPERIMENTAL

Fludarabine

Intervention Type DRUG

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

Busulfan

Intervention Type DRUG

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

Rituximab

Intervention Type DRUG

200 mg/m2 intravenous given once on day-1

Levetiracetam

Intervention Type DRUG

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.

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

Group Type EXPERIMENTAL

Fludarabine

Intervention Type DRUG

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

Busulfan

Intervention Type DRUG

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

Melphalan

Intervention Type DRUG

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

Rituximab

Intervention Type DRUG

200 mg/m2 intravenous given once on day-1

Levetiracetam

Intervention Type DRUG

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.

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.

Group Type EXPERIMENTAL

Fludarabine

Intervention Type DRUG

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

Rituximab

Intervention Type DRUG

200 mg/m2 intravenous given once on day-1

Levetiracetam

Intervention Type DRUG

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.

Thymoglobulin

Intervention Type DRUG

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.

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.

Group Type EXPERIMENTAL

Fludarabine

Intervention Type DRUG

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

Busulfan

Intervention Type DRUG

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

Rituximab

Intervention Type DRUG

200 mg/m2 intravenous given once on day-1

Levetiracetam

Intervention Type DRUG

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.

Thymoglobulin

Intervention Type DRUG

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.

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.

Group Type EXPERIMENTAL

Fludarabine

Intervention Type DRUG

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

Busulfan

Intervention Type DRUG

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

Melphalan

Intervention Type DRUG

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

Rituximab

Intervention Type DRUG

200 mg/m2 intravenous given once on day-1

Levetiracetam

Intervention Type DRUG

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.

Thymoglobulin

Intervention Type DRUG

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.

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.

Group Type EXPERIMENTAL

Busulfan

Intervention Type DRUG

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

Rituximab

Intervention Type DRUG

200 mg/m2 intravenous given once on day-1

Levetiracetam

Intervention Type DRUG

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.

Thymoglobulin

Intervention Type DRUG

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

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

Rituximab

Intervention Type DRUG

200 mg/m2 intravenous given once on day-1

Levetiracetam

Intervention Type DRUG

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.

Thymoglobulin

Intervention Type DRUG

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

Intervention Type DRUG

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

Interventions

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Fludarabine

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

Intervention Type DRUG

Busulfan

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

Intervention Type DRUG

Melphalan

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

Intervention Type DRUG

Rituximab

200 mg/m2 intravenous given once on day-1

Intervention Type DRUG

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.

Intervention Type DRUG

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.

Intervention Type BIOLOGICAL

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.

Intervention Type DRUG

Cyclophosphamide

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

Intervention Type DRUG

Other Intervention Names

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Keppra ATG

Eligibility Criteria

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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
Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Margaret MacMillan

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota Masonic Cancer Center

Locations

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University of Minnesota Masonic Cancer Center

Minneapolis, Minnesota, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Margaret MacMillan

Role: CONTACT

612-626-2961

Facility Contacts

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Margaret MacMillan

Role: primary

Other Identifiers

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2021LS061

Identifier Type: -

Identifier Source: org_study_id

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