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

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

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

• Aimee C. Talleur, MD
  866-278-5833
  [email protected]

Locations (1)

Find similar trials in Memphis, TN

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