Overview

This phase I/II trial will investigate a new CD19 directed CAR-T therapy manufactured locally with the goals to expedite infusion to wider patient inclusion that includes those who were previously excluded, such as pediatric patients with B-cell NHL and patients in primary relapse.

Eligibility

Inclusion Criteria:

1. Meets criteria for potential leukapheresis collection or has leukapheresis product previously collected and stored per recommended guidelines;
2. 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);
3. Willingness to participate in long-term follow-up study;
4. Stated willingness to comply with all study procedures and be available for the duration of the study;
5. Males OR non-pregnant, non-lactating females;
6. Aged 31 days to 30 years (inclusive) at time of consent and enrollment;
7. 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 ;
   • Meets any one of the following conditions:

             Relapsed two or more times Relapsed at any time after allogeneic 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
          8. Performance score (Lansky or Karnofsky) of 50% or better;
          9. Unable to receive commercially available CD19 CAR-T Therapy.
        Exclusion Criteria:
          1. Active, uncontrolled CNS leukemia or lymphoma, as clinically indicated, at
             eligibility, prior to lymphodepleting chemotherapy (LD chemo), and pre-cell infusion;
          2. Active Graft-versus-Host Disease (GvHD);
          3. Active, uncontrolled, life threatening infection that at the determination of the
             treating physician would preclude safe leukapheresis or tolerance of lymphodepleting
             chemotherapy, cell infusion, or cytokine release syndrome;
          4. Evidence of severe organ dysfunction that at the determination of the treating
             physician would preclude safe leukapheresis or tolerance of lymphodepleting
             chemotherapy, cell infusion, or cytokine release syndrome including any of the
             following:
               -  Myocardial dysfunction (based on age standards)
               -  Baseline oxygen saturation of < 90% on room air
               -  Diffusion capacity of the lungs for carbon monoxide (DLCO) < 40%, as determined
                  within 45 days before cell infusion
               -  Transaminases > 10x upper limit of normal (ULN) or bilirubin >2x the ULN, unless
                  thought to be related to primary disease
               -  Estimated 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 active Hepatitis C infection;
          7. Prior gene therapy, including prior CAR-T cell.