Genetically Engineered Cells (CD19- CAR.CD45RA-Negative T-cells) for the Treatment of Relapsed and/or Refractory CD19-Positive Leukemia

Inclusion Criteria

• DONORS: APHERESIS AND MANUFACTURING
• Age >= 18 years old
• At least single haplotype matched (>= 3/6) family member
• Human immunodeficiency virus (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 Code of Federal Regulations (CFR) 1271 and agency guidance
• For Cohort A only, identified recipient with relapsed and/or refractory CD19-positive leukemia
• For Cohort B only, 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 and/or CD19-antibody therapy (ex: blinatumomab) * History of prior autologous leukapheresis failure * History of prior autologous CAR T-cell manufacturing failure * Unable to undergo autologous leukapheresis and/or receive autologous CD19-CAR T cell therapy in the opinion of the study principal investigator (PI)(s): examples may include - patient small size/low weight, inadequate T-cell counts, rapidly progressive leukemia, clinical status not amenable to apheresis
• PATIENTS: TREATMENT
• Age =< 21 years old
• Relapsed and/or refractory CD19-positive leukemia*: * CD19-positivity confirmed within 2 months and after receipt of any CD19-directed therapy ** Refractory disease (primary or in relapse) ** 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
• 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
• Detectable medullary leukemia
• Estimated life expectancy of >= 8 weeks
• Karnofsky or Lansky performance score >= 50
• No central nervous system (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
• Left ventricular ejection fraction >= 40% or shortening fraction >= 25% (function may be supported by pharmacologic therapy)
• Electrocardiogram (EKG) without evidence of clinically significant arrhythmia
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 50 ml/min/1.73m^2 (GFR >= 40 ml/min/1.73m^2 if < 2 years of age)
• 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 National Cancer Institute (NCI) Common Terminology for Adverse Events (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