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

Pediatric ALL Clinical Trial

Official title: A Phase I Study Evaluating Allogeneic Memory T Cells Engineered to Express Chimeric Antigen Receptors Specific for CD19 for the Treatment of Pediatric and Young Adult Patients ≤ 21 Years of Age With Relapsed or Refractory CD19-Positive Leukemia

Status Recruiting

Clinical Trial Summary

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.

Clinical Trial Description

This is a Phase I dose escalation study using a 3+3 study design. Two groups of patients will be evaluated in this study: group A - patients have received a prior stem cell transplant from their CAR T-cell donor; group B - patients have not received a prior stem cell transplant from their CAR T-cell donor. There will be up to 30 participants per group and a donor/ family member for each patient.

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Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia, in Relapse
• Acute Lymphoblastic Leukemia, Refractory
• Leukemia
• Leukemia, Lymphoid
• Pediatric ALL
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

• NCT number: NCT04881240
• Study type: Interventional
• Source: St. Jude Children's Research Hospital
• Contact: Aimee C. Talleur, MD
• Phone: 866-278-5833
• Email: referralinfo@stjude.org
• Status: Recruiting
• Phase: Phase 1
• Start date: February 14, 2024
• Completion date: June 2027