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

  • STATUS
    Recruiting
  • End date
    Jan 11, 2026
  • participants needed
    60
  • sponsor
    St. Jude Children's Research Hospital
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Updated on 11 August 2022
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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 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.

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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Details
Condition Acute Lymphoblastic Leukemia, in Relapse, Acute Lymphoblastic Leukemia, Refractory, Pediatric ALL
Treatment cyclophosphamide, leukapheresis, Fludarabine, MESNA, CliniMACs, CD19-CAR(Mem) T-cells
Clinical Study IdentifierNCT04881240
SponsorSt. Jude Children's Research Hospital
Last Modified on11 August 2022

Eligibility

 Yes No Not Sure

Inclusion Criteria

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
Identified 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
Not suitable to receive autologous CD19-CAR T-cell therapy as defined above
Relapsed and/or refractory CD19-positive leukemia
CD19-positivity confirmed within 2 months and after receipt of any CD19-directed therapy
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)
nd or greater relapse
Any relapse after allogeneic hematopoietic cell transplantation (HCT)
st 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
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
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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