Study of CD19 Allogeneic Memory T-cell Therapy for Relapsed/Refractory CD19+ Leukemia

Part of paid clinical trials in Memphis, Tennessee.

Sponsor
St. Jude Children's Research Hospital
Study ID
NCT04881240
Phase
PHASE1
Status
Recruiting
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Conditions

  • Acute Lymphoblastic Leukemia, Refractory
  • Acute Lymphoblastic Leukemia, in Relapse
  • Pediatric ALL

Eligibility Criteria

Sex
ALL
Age
N/A - 21 Years
Healthy Volunteers
Not accepted

Interventions

  • CD19-CAR(Mem) T-cells — BIOLOGICAL
    Allogeneic CD19-CAR.CD45RA-negative T-cells Intravenous infusion
  • Cyclophosphamide — DRUG
    Cyclophosphamide is a nitrogen mustard derivative. It acts as an alkylating agent that causes cross-linking of DNA strands by binding with nucleic acids and other intracellular structures, thus interfering with the normal function of DNA.
  • Fludarabine — DRUG
    Fludarabine phosphate is a synthetic purine nucleoside analog. It acts by inhibiting DNA polymerase, ribonucleotide reductase and DNA primase by competing with the physiologic substrate, deoxyadenosine triphosphate, resulting in inhibition of DNA synthesis.
  • Mesna — DRUG
    Mesna is a synthetic sulfhydryl (thiol) compound. Mesna contains free sulfhydryl groups that interact chemically with urotoxic metabolites of oxaza-phosphorine derivatives such as cyclophosphamide and ifosfamide.
  • CliniMACS — DEVICE
    A CliniMACS device is used to select donor T-cells for manufacturing of the memory CAR T-cell product.
  • Leukapheresis — PROCEDURE
    Leukapheresis is performed to collect the T cells that are needed to generate the CD19-CAR.CD45RA-negative T-cells product for the clinic study.

Study Details

This is a Phase I clinical study evaluating the safety and maximum tolerated dose of a novel CAR T-cell product: allogeneic memory (CD45RA- negative) T-cells expressing a CD19-specific CAR 41BBz (CD19-CAR.CD45RA- negative T-cells) for the treatment of patients ≤ 21 years old with relapsed and/ or refractory CD19-positive leukemia. Primary Objective To determine the maximum tolerated dose (MTD) and characterize the safety profile and dose-limiting toxicities (DLTs) of treatment with allogeneic CD19-CAR.CD45RA-negative T-cells in pediatric, adolescent and young adult patients ≤ 21 years of age, with relapsed and/or refractory CD19-positive leukemia. Secondary Objectives * To evaluate the anti-leukemic activity of allogeneic CD19-CAR.CD45RA-negative T-cells. * To determine rates and severity of graft-versus-host-disease (GVHD) after treatment with allogeneic CD19-CAR.CD45RA-negative T-cells. Exploratory Objectives * To study the expansion, persistence and phenotype of allogeneic CD19-CAR.CD45RA-negative T-cells. * To characterize the cytokine profile in the peripheral blood and CSF after treatment with allogeneic CD19-CAR.CD45RA-negative T-cells. * To assess whether allogeneic CD19-CAR.CD45RA-negative T-cells acquire functional versus exhaustion-associated epigenetic programs. * To determine immune reconstitution post treatment, and the clonal structure and endogenous repertoire of allogeneic CD19-CAR.CD45RA-negative T-cells and relate inferred specificity to CAR response profiles. * To characterize incidence and mechanisms of relapse post-therapy with allogeneic CD19-CAR.CD45RA-negative T-cells.

Key Dates

First listed
May 11, 2021
Start date
Feb 14, 2024
Status verified
May 2026
Primary completion
Jul 1, 2027
Completion
Jul 1, 2028

Study Design

Enrollment
60 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Group A
    Participants in group A have received a prior stem cell transplant from their CAR T-cell donor.
  • Experimental: Group B
    Participants in group B have not received a prior stem cell transplant from their CAR T-cell donor.

Primary Outcome Measure

Maximum tolerated dose of allogeneic, CD19-CAR.CD45RA-negative cells [ Time Frame: 4 weeks after CAR T-cell infusion ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
St. Jude Children's Research HospitalMemphisTennessee38105
Aimee C. Talleur, MD
[email protected]
866-278-5833
Aimee C. Talleur, MD (PRINCIPAL_INVESTIGATOR)
Stephen Gottschalk, MD (PRINCIPAL_INVESTIGATOR)

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