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

Phase 1

Recruiting

• Conditions: Acute Lymphoblastic Leukemia, in Relapse; Pediatric ALL; Acute Lymphoblastic Leukemia, Refractory
• Interventions: Biological: CD19-CAR(Mem) T-cells; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Mesna; Device: CliniMACS; Procedure: Leukapheresis

• Registration Number: NCT04881240
• Lead Sponsor: St. Jude Children's Research Hospital

Brief 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.

Detailed 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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Study Timeline

• Study First Submitted: 2021-04-27
• Study First Submitted QC: 2021-05-05
• Study First Posted: 2021-05-11
• Study Start: 2024-02-14
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-15
• Last Update Posted: 2025-01-17
• Primary Completion: 2026-06
• Study Completion: 2027-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Not provided

Exclusion Criteria

NA

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A	CD19-CAR(Mem) T-cells	Participants in group A have received a prior stem cell transplant from their CAR T-cell donor.
Group B	Leukapheresis	Participants in group B have not received a prior stem cell transplant from their CAR T-cell donor.
Group A	CliniMACS	Participants in group A have received a prior stem cell transplant from their CAR T-cell donor.
Group A	Leukapheresis	Participants in group A have received a prior stem cell transplant from their CAR T-cell donor.
Group B	CD19-CAR(Mem) T-cells	Participants in group B have not received a prior stem cell transplant from their CAR T-cell donor.
Group B	CliniMACS	Participants in group B have not received a prior stem cell transplant from their CAR T-cell donor.
Group A	Cyclophosphamide	Participants in group A have received a prior stem cell transplant from their CAR T-cell donor.
Group A	Mesna	Participants in group A have received a prior stem cell transplant from their CAR T-cell donor.
Group A	Fludarabine	Participants in group A have received a prior stem cell transplant from their CAR T-cell donor.
Group B	Fludarabine	Participants in group B have not received a prior stem cell transplant from their CAR T-cell donor.
Group B	Cyclophosphamide	Participants in group B have not received a prior stem cell transplant from their CAR T-cell donor.
Group B	Mesna	Participants in group B have not received a prior stem cell transplant from their CAR T-cell donor.

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose of allogeneic, CD19-CAR.CD45RA-negative cells	4 weeks after CAR T-cell infusion	This phase I study includes dose escalation/de-escalation based on dose limiting toxicity (DLT) assessment to determine the maximum tolerated dose (MTD) of allogeneic, CD19-CAR.CD45RA-negative cells.

Trial Locations

Locations (1)

St. Jude Children's Research Hospital; 🇺🇸 Memphis, Tennessee, United States