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

NCT04881240 | Recruiting Phase 1 FDA Drug

• 1 other identifier: MEMCAR19
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of allogeneic, CD19-CAR.CD45RA-negative cells

  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.

  4 weeks after CAR T-cell infusion

Study Arms (2)

Group A

EXPERIMENTAL

Participants in group A have received a prior stem cell transplant from their CAR T-cell donor.

Biological: CD19-CAR(Mem) T-cells; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Mesna; Device: CliniMACS; Procedure: Leukapheresis

Group B

EXPERIMENTAL

Participants in group B have not received a prior stem cell transplant from their CAR T-cell donor.

Biological: CD19-CAR(Mem) T-cells; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Mesna; Device: CliniMACS; Procedure: Leukapheresis

Interventions

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.

Group A; Group B

CD19-CAR(Mem) T-cells BIOLOGICAL

Allogeneic CD19-CAR.CD45RA-negative T-cells Intravenous infusion

Group A; Group B

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.

Also known as: Cytoxan

Group A; Group B

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.

Also known as: Fludara

Group A; Group B

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.

Also known as: Mesnex

Group A; Group B

CliniMACS DEVICE

A CliniMACS device is used to select donor T-cells for manufacturing of the memory CAR T-cell product.

Group A; Group B

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age ≥ 18 years old
• At least single haplotype matched (≥ 3/6) family member
• HIV negative
• For females of child bearing age: Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment AND Not lactating with intent to breastfeed
• Completed the process of donor eligibility determination as outlined in 21 CFR 1271 and agency guidance
• For Cohort A only, identified recipient with relapsed and/or refractory CD19-positive leukemia
• For Cohort B only, iIdentified recipient with relapsed and/or refractory CD19-positive leukemia who is not suitable to receive autologous CD19-CAR T-cell therapy as defined by the following:
• Relapsed and/or refractory disease despite prior treatment with autologous CD19- CAR T-cell therapy
• History of prior autologous leukapheresis failure
• History of prior autologous CAR T-cell manufacturing failure
• Unable to undergo autologous leukapheresis in the opinion of the study PI(s): examples may include - patient small size/low weight, inadequate T-cell counts, rapidly progressive leukemia, clinical status not amenable to apheresis
• Eligibility Criteria for Patients: Treatment
• Age ≤ 21 years old
• Relapsed and/or refractory CD19-positive leukemia\*:
• Refractory disease (defined as any of the following):

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; Mesna; Leukapheresis

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques

Study Officials

• Aimee C. Talleur, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

• Stephen Gottschalk, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aimee C. Talleur, MD

CONTACT

866-278-5833; referralinfo@stjude.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2021
• First Posted: May 11, 2021
• Study Start: February 14, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2028
• Last Updated: December 23, 2025

Record last verified: 2025-12

Locations

US (1)