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

Sponsor
Masonic Cancer Center, University of Minnesota (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05735717
Collaborator
(none)
150
3
91.7

Study Details

Study Description

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

Study Design

Study Type:
Interventional
Anticipated Enrollment :
150 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II, Open-Label, Prospective Study of T Cell Receptor Alpha/Beta Depletion (A/B TCD) Peripheral Blood Stem Cell (PBSC) Transplantation for Children and Adults With Hematological Malignancies
Anticipated Study Start Date :
Apr 9, 2023
Anticipated Primary Completion Date :
Nov 30, 2027
Anticipated Study Completion Date :
Nov 30, 2030

Arms and Interventions

Arm Intervention/Treatment
Experimental: Fludarabine (flu), Total Body Irradiation (TBI), Flu/TBI Regimen

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.

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

Drug: Rituximab
200 mg/m2 intravenous given once on day-1

Experimental: Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen

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.

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

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

Drug: Rituximab
200 mg/m2 intravenous given once on day-1

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.
Other Names:
  • Keppra
  • Experimental: 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.

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

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

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

    Drug: Rituximab
    200 mg/m2 intravenous given once on day-1

    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.
    Other Names:
  • Keppra
  • Outcome Measures

    Primary Outcome Measures

    1. Determine the rate of GVHD after alpha beta TCR depletion [85 months]

      GVHD incidence after treatment.

    Secondary Outcome Measures

    1. Transplant engraftment [42 days]

      Monitor median rate of engraftment by 42 days.

    2. 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)

    3. Non-relapse mortality (NRM) [12 months]

      Determine the incidence of non-relapse mortality (NRM) at 100 days and 1 year

    4. Overall survival (OS) [12 months]

      Number of participants experiencing progression free survival at one year follow up

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A to 60 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Masonic Cancer Center, University of Minnesota

    Investigators

    • Principal Investigator: Najla El Jurdi, University of Minnesota Masonic Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Masonic Cancer Center, University of Minnesota
    ClinicalTrials.gov Identifier:
    NCT05735717
    Other Study ID Numbers:
    • 2021LS061
    First Posted:
    Feb 21, 2023
    Last Update Posted:
    Feb 21, 2023
    Last Verified:
    Feb 1, 2023
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Masonic Cancer Center, University of Minnesota
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Feb 21, 2023