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

October 2, 2023 updated by: Masonic Cancer Center, University of Minnesota

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

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 Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

150

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Recruiting
        • University of Minnesota Masonic Cancer Center
        • Contact:
          • Margaret MacMillan

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 60 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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: Rituximab
200 mg/m2 intravenous given once on day-1
Drug: Busulfan
Busulfan 82.1 mg*hr/L IV on days -5 to -2 or days -8 to -5
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: Rituximab
200 mg/m2 intravenous given once on day-1
Drug: Busulfan
Busulfan 82.1 mg*hr/L IV on days -5 to -2 or days -8 to -5
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
Drug: Melphalan
Melphalan 50 mg/m2 IV on days -4 to -2

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine the rate of GVHD after alpha beta TCR depletion
Time Frame: 85 months
GVHD incidence after treatment.
85 months

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Masonic Cancer Center, University of Minnesota

Investigators

  • Principal Investigator: Margaret MacMillan, University of Minnesota Masonic Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 11, 2023

Primary Completion (Estimated)

November 30, 2027

Study Completion (Estimated)

November 30, 2030

Study Registration Dates

First Submitted

January 10, 2023

First Submitted That Met QC Criteria

February 9, 2023

First Posted (Actual)

February 21, 2023

Study Record Updates

Last Update Posted (Actual)

October 3, 2023

Last Update Submitted That Met QC Criteria

October 2, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2021LS061

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

For the purposes of data and safety monitoring, this study is classified as high risk (investigator initiated under an IND). Therefore the following requirements will be fulfilled:

  • The Masonic Cancer Center Data and Safety Monitoring Council (DSMC) will review the study's progress at least quarterly.
  • The PI will comply with at least twice yearly monitoring of the project by the Masonic Cancer Center monitoring services.
  • The PI will oversee the submission of all reportable adverse events per the definition of reportable in Section 11.5 to the Masonic Cancer Center's SAE Coordinator, the University of Minnesota IRB, and the FDA.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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