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

University of Minnesota (UMN)

Status and phase: Enrolling; Phase 2

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

Treatments: Drug: Thymoglobulin; Drug: Levetiracetam; Drug: Fludarabine; Drug: Busulfan; Drug: Cyclophosphamide; Drug: Melphalan; Drug: Rituximab; Biological: Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells

Study type: Interventional

Funder types: Other

Identifiers

NCT05735717

2021LS061

Details and patient eligibility

About

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.

Enrollment: 70 estimated patients

Sex: All

Ages: Under 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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70 participants in 8 patient groups

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

Experimental group

Description:

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.

Treatment:

Biological: Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells

Drug: Rituximab

Drug: Fludarabine

Drug: Levetiracetam

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

Experimental group

Description:

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.

Treatment:

Drug: Rituximab

Drug: Busulfan

Drug: Fludarabine

Drug: Levetiracetam

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

Experimental group

Description:

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

Treatment:

Drug: Rituximab

Drug: Melphalan

Drug: Busulfan

Drug: Fludarabine

Drug: Levetiracetam

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

Experimental group

Description:

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.

Treatment:

Drug: Rituximab

Drug: Fludarabine

Drug: Levetiracetam

Drug: Thymoglobulin

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

Experimental group

Description:

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.

Treatment:

Drug: Rituximab

Drug: Busulfan

Drug: Fludarabine

Drug: Levetiracetam

Drug: Thymoglobulin

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

Experimental group

Description:

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

Treatment:

Drug: Rituximab

Drug: Melphalan

Drug: Busulfan

Drug: Fludarabine

Drug: Levetiracetam

Drug: Thymoglobulin

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

Experimental group

Description:

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.

Treatment:

Drug: Rituximab

Drug: Cyclophosphamide

Drug: Busulfan

Drug: Levetiracetam

Drug: Thymoglobulin

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

Experimental group

Description:

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.

Treatment:

Drug: Rituximab

Drug: Cyclophosphamide

Drug: Levetiracetam

Drug: Thymoglobulin