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

MEMCAR19

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.

2024-02-14

2026-06-01

2027-06-01

Recruiting

Early phase I

60

Inclusion Criteria Eligibility Criteria for Donors: Apheresis and Manufacturing * 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): * Primary refractory disease despite at least 2 cycles of an intensive chemotherapy regimen designed to induce remission * Refractory disease despite salvage therapy * Relapsed disease (defined as any of the following): * 2nd or greater relapse * Any relapse after allogeneic hematopoietic cell transplantation (HCT) * 1st relapse if patient requires an allogeneic HCT as part of standard of care relapse therapy, but is found to be ineligible and/or unsuitable for HCT CD19-positivity confirmed within 2 months and after receipt of any CD19-directed therapy * Patient cohorts: * Cohort A: patient has previously received a HCT from the selected CAR T-cell donor * Cohort B - patient has NOT previously received a HCT from the selected CAR T-cell donor. * For Cohort B only, not suitable to receive autologous CD19-CAR T-cell therapy as defined above in Criteria: Eligibility Criteria for Donors: Apheresis and Manufacturing * Detectable medullary CD19-positive leukemia * Estimated life expectancy of ≥ 8 weeks * Karnofsky or Lansky performance score ≥ 50 * No CNS-3 disease or any level of detectable leukemia in CNS with associated neurologic symptoms * If history of allogeneic HCT (regardless of donor type), prior to planned CAR T-cell infusion, must meet the following criteria: * ≥ 3 months from HCT * have recovered from prior HCT therapy * have no evidence of active GVHD within prior 2 months * have not received a donor lymphocyte infusion (DLI) within the 28 days prior to planned CAR T-cell infusion * Adequate cardiac function: left ventricular ejection fraction ≥ 40% or shortening fraction ≥ 25% (function may be supported by pharmacologic therapy) * EKG without evidence of clinically significant arrhythmia * Adequate renal function: creatinine clearance or radioisotope GFR 50 ml/min/1.73m2 (GFR 40 ml/min/1.73m2 if \< 2 years of age) * Adequate pulmonary function: forced vital capacity (FVC) ≥ 50% of predicted value; or pulse oximetry ≥ 92% on room air if patient is unable to perform pulmonary function testing * Total bilirubin ≤ 3 times the upper limit of normal for age, except in subjects with Gilbert's syndrome * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 5 times the upper limit of normal for age * No history of HIV infection * No evidence of severe, uncontrolled bacterial, viral or fungal infection * Has recovered from all NCI CTAE grade III-IV, non-hematologic acute toxicities from prior therapy * For females of child bearing age: * Not pregnant with negative serum or urine pregnancy test ≤ 7 days prior to enrollment AND Not lactating with intent to breastfeed * If sexually active, agreement to use birth control until 6 months after CAR T-cell infusion * No history of hypersensitivity reactions to murine protein-containing products * Not receiving systemic steroids therapy exceeding the equivalent of 0.5 mg/kg/day of methylprednisolone ≤ 7 days prior to CAR T-cell infusion * Not receiving systemic therapy ≤ 14 days prior to CAR T-cell infusion, which will interfere with the activity of the CAR T-cell product in vivo (in the opinion of the study PI(s)) * Not receiving intrathecal chemotherapy ≤ 7 days prior to CAR T-cell infusion Exclusion Criteria: NA

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2024-03-06