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

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• NA

• 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, an ineligible donor may be used under urgent medical need if the reason for ineligibility was previously present at time of transplant determination.
  • 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: Pre-Treatment Evaluation*
  • Inclusion
• MEMCAR19 recipient candidate ≤<21 years old with rRelapsed and/or refractory CD19-positive leukemia.
  • *Due to potential scheduling challenges, all recipients may not be offered the Pre-Treatment Evaluation consent. This will not be counted as a deviation.
  • 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