CD19x22 CAR T Cells for the Treatment of Pediatric Patients with Relapsed and/or Refractory B-Cell Acute Lymphoblastic Leukemia

Inclusion Criteria

• Subjects must have a history of B precursor ALL with any of the following conditions: * Relapsed two or more times * Relapsed at any time after allogeneic bone marrow transplant (BMT) * Relapse or refractory after single antigen targeting CAR T cell therapy ** 30 days must have elapsed post previous CAR infusion prior to apheresis ** The subject’s previous CAR T cell therapy must be < 5% of circulating CD3+ cells in the peripheral blood by flow cytometry (e.g. detection of FMC63 scFv by flow cytometry) * Refractory to standard therapy as determined by the treating physician * Patient and/or parents declining BMT options and would prefer CAR T Therapy
• CD19 and/or CD22 present on last relapsed/refractory disease evaluation
• Performance score (Lansky or Karnofsky ≥ 50%; or Eastern Cooperative Oncology Group [ECOG] must be ≤ 2)
• Meets criteria for potential leukapheresis collection or has leukapheresis product previously collected and stored per recommended guidelines
• Males OR non-pregnant, non-lactating females
• Aged 3 months to 30 years (inclusive) at time of consent and enrollment
• Provision of a signed and dated consent form from parent or guardian (patients < 18), the patient themselves (> 18), or legally authorized representative (for patients who lack decision-making capacity) after standard of care (SOC) screening assessments are performed
• Stated willingness to comply with all study procedures and be available for the duration of the study
• Willingness to participate in long-term follow-up protocol (20-0188)

Exclusion Criteria

• Active, uncontrolled central nervous system (CNS) leukemia as determined by the treating physician at eligibility, prior to lymphodepleting chemotherapy (LD chemo), and pre- CD19x22 CAR T cell infusion
• History of allogeneic stem cell transplantation prior to apheresis that meet the following criteria: * Less than 100 days post-transplant * Evidence of active graft-versus-host disease (GvHD) requiring systemic therapy * Less than 6 weeks post donor lymphocyte infusion (DLI)
• Active, uncontrolled, life-threatening infection that at the determination of the treating physician would preclude safe apheresis or tolerance of lymphodepleting chemotherapy, cell infusion, or increased risk of cytokine release syndrome
• Evidence of severe organ dysfunction that at the determination of the treating physician would preclude safe apheresis or tolerance of lymphodepleting chemotherapy, cell infusion, or cytokine release syndrome including: * Myocardial dysfunction (based on age standards) * Baseline oxygen saturation of < 90% on room air * Ejection fraction < 40, evidence of physiologically significant pericardial effusion as determined by an echocardiogram (ECHO), and clinically significant electrocardiogram (ECG) findings * Transaminases > 10 x upper limit of normal (ULN) or bilirubin > 5 x the ULN, unless thought to be related to primary disease * Estimated Creatinine (Cr) clearance < 60 mL/min/1.73 m^2 (if nuclear medicine glomerular filtration rate [GFR] or other more specific testing exceeds this level than it can supersede the estimated clearance)
• Post-pubertal females that are pregnant, planning to become pregnant, or unwilling to use birth control (includes abstinence) for the study duration
• Known HIV infection or active hepatitis B or hepatitis C infection