Genetically Engineered Cells (UCD19 CAR-T Cells) for the Treatment of Recurrent or Refractory B-cell Acute Lymphoblastic Leukemia or B-cell Non-Hodgkin Lymphoma

Inclusion Criteria

• Meets criteria for potential leukapheresis collection or has leukapheresis product previously collected and stored per recommended guidelines
• Provision of 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); Pediatric patients will be included in age-appropriate discussions and assent will be obtained for those > 7 years of age, when appropriate, according to institutional standards.
• Willingness to participate in long term follow up study
• Stated willingness to comply with all study procedures and be available for the duration of the study
• Males OR non-pregnant, non-breastfeeding females * Patients of child-bearing potential or capable of fathering a child must agree to use highly effective contraception from the time of initial CAR T cell administration though 12 months following the final administration of investigational product
• Aged 31 days to 30 years (inclusive) at time of consent and enrollment
• Acute lymphoblastic leukemia (ALL) OR non-Hodgkin lymphoma (NHL) of B-cell origin that: * Has confirmed expression of CD19 by flow cytometry, immunohistochemistry (IHC), or both * COHORT ONE CRITERIA: ** Meets any one of the following conditions: *** Relapsed two or more times *** Relapsed at any time after allogeneic bone marrow transplant (BMT) *** Refractory to standard therapy as determined by the treating physician *** Meets criteria for BMT but is ineligible as determined by the treating physician *** Patient and/or parents declining BMT options and would prefer CAR-T Therapy ** Non-Hodgkin lymphoma includes all of the following: *** Diffuse large B-cell lymphoma (DLBCL) *** Burkitt lymphoma *** Intermediate lymphoma between Burkitt and DLBCL *** Primary mediastinal B-cell lymphoma (PMBL) *** Follicular lymphoma *** High grade B cell lymphoma *** Transformed lymphoma * COHORT TWO CRITERIA: ** B-ALL in first relapse with any one of the following conditions: *** High-risk genomic alterations at initial diagnosis such as KMT2A gene rearrangement, t(17;19), hypodiploidy, Ph-like mutations, BCR-ABL1 fusion (Ph+ ALL), iAMP21, and TP53 inactivating mutation/deletion *** Isolated CNS relapse such that cranial radiation would be indicated as a component of standard salvage therapy *** Down syndrome *** Minimal residual disease (MRD) positivity of > 0.01% by fluorescence activated cell sorting (FACS) or > 0 clonal sequences by next generation sequencing (NGS) in bone marrow post re-induction chemotherapy *** Age 18 years or older. OR ** Newly diagnosed with persistent MRD ≥ 0.01% by flow cytometry in bone marrow at end of consolidation.
• Performance score (Lansky or Karnofsy) of 50% or better
• Unable to or declined to receive commercially available CD19 CAR-T therapy

Exclusion Criteria

• Evidence of rapidly progressive disease without adequate salvage/bridging regimens as determined by the investigator.
• Active graft-versus-host disease (GvHD)
• 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 cytokine release syndrome
• Evidence of severe organ dysfunction as defined by: * Myocardial dysfunction: 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 * Baseline oxygen saturation of ≤ 90% on room air * Transaminases > 10 x upper limit of normal (ULN) or bilirubin > 2 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 human immunodeficiency virus (HIV) infection, or active hepatitis B or active hepatitis C infection
• Prior gene therapy, including prior CAR-T cell