CD19x22 Chimeric Antigen Receptor T-cell Therapy (CAR T) in Pediatric B-ALL

Eligibility Criteria

• 1. Subjects must have a history of B precursor ALL with any of the following conditions:
• 1. Relapsed two or more times.
• 2. Relapsed at any time after allogeneic bone marrow transplant (BMT).
• 3. Relapse or refractory after single antigen targeting CAR T cell therapy.
• 2. CD19 and/or CD22 present on last relapsed/refractory disease evaluation.
• 3. Performance score (Lansky or Karnofsky ≥ 50%; or Eastern Cooperative Oncology Group (ECOG) must be ≤2).
• 4. Meets criteria for potential leukapheresis collection or has leukapheresis product previously collected and stored per recommended guidelines.
• 5. Males OR non-pregnant, non-lactating females.
• 6. Aged 3 months to 30 years (inclusive) at time of consent and enrollment.
• 7. Provision of a signed and dated consent form from parent or guardian (patients \< 18), the patient themselves (\> 18), or legally authorized representative (patient \> 18 who lack decision-making capacity) after standard of care (SOC) screening assessments are performed.
• 8. Stated willingness to comply with all study procedures and be available for the duration of the study.
• 9. Willingness to participate in long-term follow-up protocol.
• 1. 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.
• 2. History of allogeneic stem cell transplantation prior to apheresis that meet the following criteria:
• 1. Less than 100 days post-transplant;
• 2. Evidence of active Graft-versus-Host Disease (GvHD) requiring systemic therapy;
• 3. Less than 6 weeks post donor lymphocyte infusion (DLI).
• 3. 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.
• 4. Evidence of severe organ dysfunction defined by:
• 1. Baseline oxygen saturation of \< 90% on room air
• 2. Myocardial dysfunction (based on age standards): Ejection fraction ≤\< 40% or shortening fraction ≤ 28%,, evidence of physiologically significant pericardial effusion as determined by an echocardiogram (ECHO), and clinically significant electrocardiogram (ECG) findings
• 3. Transaminases \> 10x upper limit of normal (ULN) or bilirubin \> 5x the ULN, unless thought to be related to primary disease
• 4. Estimated Creatinine (Cr) clearance \< 60 mL/min/1.73 m2 (if nuclear medicine GFR or other more specific testing exceeds this level than it can supersede the estimated clearance)
• 5. Post-pubertal females that are pregnant, planning to become pregnant, or unwilling to use birth control (includes abstinence) for the study duration.
• 6. Known HIV infection or active Hepatitis B or Hepatitis C infection.