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

Launched by ST. JUDE CHILDREN'S RESEARCH HOSPITAL · May 5, 2021

Keywords

ClinConnect Summary

This clinical trial is studying a new type of treatment called CD19-directed allogeneic memory T-cell therapy for children and young adults up to 21 years old who have leukemia that has come back or has not responded to previous treatments. The goal is to find out how safe this therapy is, how much of it can be given without causing serious side effects, and to see how well it works against leukemia. Participants will receive specially modified T-cells (a type of immune cell) that are designed to target and destroy leukemia cells.

To be eligible for this trial, participants must have relapsed or refractory CD19-positive leukemia and be younger than 21. They should also have a specific type of T-cell donor available. Throughout the trial, participants will be closely monitored for any side effects and how their body responds to the treatment. It's important to know that this is an early-stage study, which means it's one of the first steps in testing this new therapy to ensure it's safe and potentially effective for young patients with challenging forms of leukemia.

Gender

ALL

Eligibility criteria

• • 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