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

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 orurine pregnancy test within 14 days prior to enrollment AND Not lactating withintent to breastfeed

• Completed the process of donor eligibility determination as outlined in 21 CFR 1271and 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- CART-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 intensivechemotherapy 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 ofcare relapse therapy, but is found to be ineligible and/or unsuitable forHCT

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-celldonor

• Cohort B - patient has NOT previously received a HCT from the selected CART-cell donor.

• For Cohort B only, not suitable to receive autologous CD19-CAR T-cell therapy asdefined above in Criteria: Eligibility Criteria for Donors: Apheresis andManufacturing

• 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 associatedneurologic symptoms

• If history of allogeneic HCT (regardless of donor type), prior to planned CAR T-cellinfusion, 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 toplanned CAR T-cell infusion

• Adequate cardiac function: left ventricular ejection fraction ≥ 40% or shorteningfraction ≥ 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 pulmonaryfunction testing

• Total bilirubin ≤ 3 times the upper limit of normal for age, except in subjects withGilbert's syndrome

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 5 times theupper 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 fromprior therapy

• For females of child bearing age:

• Not pregnant with negative serum or urine pregnancy test ≤ 7 days prior toenrollment AND Not lactating with intent to breastfeed

• If sexually active, agreement to use birth control until 6 months after CAR T-cellinfusion

• No history of hypersensitivity reactions to murine protein-containing products

• Not receiving systemic steroids therapy exceeding the equivalent of 0.5 mg/kg/day ofmethylprednisolone ≤ 7 days prior to CAR T-cell infusion

• Not receiving systemic therapy ≤ 14 days prior to CAR T-cell infusion, which willinterfere with the activity of the CAR T-cell product in vivo (in the opinion of thestudy PI(s))

• Not receiving intrathecal chemotherapy ≤ 7 days prior to CAR T-cell infusion

Exclusion Criteria:

NA