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

Phase 2RecruitingNCT05735717

Masonic Cancer Center, University of Minnesota70 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hematologic Malignancy Acute Leukemia Remission Acute Myeloid Leukemia Acute Lymphoblastic Leukemia AML

Interventions

FludarabineDRUG

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

BusulfanDRUG

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

MelphalanDRUG

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

RituximabDRUG

200 mg/m2 intravenous given once on day-1

LevetiracetamDRUG

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 CellsBIOLOGICAL

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.

ThymoglobulinDRUG

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.

CyclophosphamideDRUG

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

Eligibility

Sex: ALLMax age: 60 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Determine the rate of GVHD after alpha beta TCR depletion

GVHD incidence after treatment.

Time frame: 100 days

Secondary Outcomes

Transplant engraftment

Monitor median rate of engraftment by 42 days.

Time frame: 42 days

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

Non-relapse mortality (NRM)

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

Time frame: 12 months

Overall survival (OS)

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