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: Melphalan; Drug: Levetiracetam

• 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 (α/β TCD) peripheral blood stem cell (PBSC) transplantation for children and adults with hematological malignancies

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: 2024-10
• Last Update Submitted: 2024-10-17
• Last Update Posted: 2024-10-21
• Primary Completion: 2027-11-30
• Study Completion: 2030-11-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 150

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
Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen	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.
Fludarabine (flu), Total Body Irradiation (TBI), Flu/TBI Regimen	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.
Fludarabine (flu), Total Body Irradiation (TBI), Flu/TBI Regimen	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.
Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen	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.
Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen	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.
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.
Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen	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.
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.
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.
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.
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.

Primary Outcome Measures

Name	Time	Method
Determine the rate of GVHD after alpha beta TCR depletion	85 months	GVHD incidence after treatment.

Secondary Outcome Measures

Name	Time	Method
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
Non-relapse mortality (NRM)	12 months	Determine the incidence of non-relapse mortality (NRM) at 100 days and 1 year
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