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

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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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