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

Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
AgeUp to 60
SponsorMasonic Cancer Center, University of Minnesota

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Histological confirmation of hematological malignancies

Acute leukemias

Acute Myeloid Leukemia (AML) and related precursor neoplasms

Acute lymphoblastic leukemia (ALL)/lymphoma

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • Fludarabine

    Drug

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

  • Busulfan

    Drug

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

  • Melphalan

    Drug

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

  • Rituximab

    Drug

    200 mg/m2 intravenous given once on day-1

  • Levetiracetam

    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

    Biological/Vaccine

    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.

  • Thymoglobulin

    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

    Drug

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

Treatment groups

70 Participants
are divided into 8 treatment groups

8

Treatment groups

See each treatment group below.

Group A: Arm 1A: Fludarabine (flu), Total Body Irradiation (TBI), Flu/TBI Regimen, Closed to AccrualExperimental treatment 4 interventions
Group B: Arm 2A: Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen, Closed to AccrualExperimental treatment 4 interventions
Group C: Arm 3A: Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients OnlyExperimental treatment 5 interventions
Group D: Arm 1B: ATG, Fludarabine (flu), Total Body Irradiation (TBI), Flu/TBI RegimenExperimental treatment 4 interventions
Group E: Arm 2B: ATG, Fludarabine (flu), Busulfan (bu), Flu/Bu RegimenExperimental treatment 5 interventions
Group F: Arm 3B: ATG, Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients OnlyExperimental treatment 6 interventions
Group G: Arm 4B: ATG, Busulfan (BU), Cyclophosphamide (CY)Experimental treatment 5 interventions
Group H: Arm 5B: ATG, Cyclophosphamide (CY), Total Body Irradiation (TBI)Experimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

Determine the rate of GVHD after alpha beta TCR depletion

GVHD incidence after treatment.

Time frame
100 days

Secondary outcomes

1

Transplant engraftment

Monitor median rate of engraftment by 42 days.

Time frame
42 days
2

Graft Failure

Determine the rate of graft failure by day 100 (defined as lack of achievement of an ANC \>=500/mL with associated pancytopenia)

Time frame
100 days
3

Non-relapse mortality (NRM)

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

Time frame
12 months
4

Overall survival (OS)

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

Time frame
12 months

Other outcomes

Sponsors and contacts

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