Local Manufacture of CAR T-Cell Products for the Treatment of B-Cell Lymphoma and B-Acute Lymphoblastic Leukemia

Inclusion Criteria

• •1. Subjects with CD19+ B-cell lymphoma or B-Cell Acute Lymphoblastic Leukemia (B-ALL) with no currently available curative treatment option (such as autologous or allogeneic Hematopoietic stem cell transplantation (HSCT)) who have a limited prognosis (\<2-year projected survival) will be enrolled. Participation on this trial is permitted as a bridge to HSCT.
• •2. Peripheral blood CD3 count \> 200/µL by flow cytometry. Please note that this test might need to be repeated multiple times as standard practice to optimize collection efficiency.
• •3. Subjects will have a diagnosis of Diffuse Large B Cell Lymphoma (DLBCL), Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL), CLL, Marginal Zone Lymphoma (MZL), Lymphoplasmacytic Lymphoma (LPL) or B-ALL and will have failed at least 2 lines of therapy in the case of lymphoma and one line if the diagnosis is B-ALL or be refractory (no response or progressive disease) to first line therapy. A line of therapy must include conventional (immuno) chemotherapy (e.g. rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHOP) or Bendamustine plus Rituximab (BR) in the case of lymphoma) administered for at least 2 cycles. Second or greater lines of therapy must be administered for at least two cycles. Single agent anti-CD20 monoclonal antibody (e.g. rituximab, obinutuzumab) is not considered for the purposes of these criteria to count as a line of therapy. The definition of a line of therapy is taken according to recommended regimens for first and second line therapy in the relevant sections of the National Comprehensive Cancer Network (NCCN) guidelines. The most recent version of the guidelines will be used for eligibility determination. In the unlikely event that a subject received a first or second line regimen no longer listed in the most recent guidelines, but previously present in the version of the guidelines active at the time the therapy was administered, then the subject would be deemed to have received a line of therapy.
• •4. Subjects with pathological and clinical evidence of transformed indolent lymphoma (FL, CLL, MZL or LPL) are eligible for participation on this trial if they have received at least one line of therapy for transformed disease for at least two cycles regardless of response.
• •5. Demonstration of CD19 expression by immunohistochemistry or flow cytometry on a pathological specimen of lymphoma or ALL cells at any time in the course of prior treatment.
• •6. Subjects who are unable to receive commercially available CD19-CAR T-cell therapy.
• •5. Active bacterial, fungal or viral infection.
• •6. Concurrent second malignancy requiring active therapy. Patients with breast or prostate cancer stable on hormonal therapy might be considered for participation if otherwise unimpaired.
• •7. Documented myocardial infarction within 6 months of study participation and/or symptomatic coronary artery or valvular disease or uncontrolled arrhythmia.
• •8. Investigational drug use within 30 days before leukapheresis.
• •9. Anti-cancer therapy administration within 4 weeks of leukapheresis including antiCD19 directed therapy, monoclonal antibody therapy, bi-specific T-cell engager therapy and targeted therapy such as Abelson tyrosine kinase inhibitors, Bruton's tyrosine kinase inhibitors, venetoclax and Lenalidomide or other IMiD (Immunomodulatory Drug).
• •10. Involved field radiation therapy is permitted if it terminates at least 15 days before leukapheresis and associated toxicity is grade 2 or less. Radiation therapy within 14 days of leukapheresis would make the subject ineligible.
• •11. Checkpoint inhibitor therapy within 4 weeks before leukapheresis.
• •12. Corticosteroid therapy at pharmacological dose (\> 10 mg of prednisone or biological equivalent) within 4 weeks before leukapheresis.
• •13. Immunosuppressive therapy that cannot be stopped for 4 weeks prior to leukapheresis as deemed by the prescribing physician.
• •14. Laboratory abnormalities that indicate clinically significant hematological, hepatobiliary, or renal disease:
• •AST (Aspartate transaminase)/SGOT(serum glutamic-oxaloacetic transaminase) \> 2.0 times the upper limit of normal ALT (alanine aminotransferase)/SGPT (serum glutamic-pyruvic transaminase) \> 2.0 times the upper limit of normal Total bilirubin \> 2.0 times the upper limit of normal, unless subject has Gilbert's Syndrome (\>3.0 times the upper limit of normal) Hemoglobin \< 8 gm/dL or dependent upon transfusion to maintain ≥ 8 gm/dL White blood cell count \< 2,000/mm3 Platelet count \< 50,000/mm3 or dependent upon transfusion to maintain ≥ 50,000 mm Creatinine \> 2.0 times the upper limit of normal or calculated creatinine clearance ≤ 40 mL/min.
• •15. Pregnant or lactating females.
• •16. Subjects who, in the opinion of the Investigator, will be non-compliant with study schedules or procedures.
• •17. Subjects who belong to a vulnerable population such as the homeless, the developmentally disabled and prisoners or have any condition that impairs their ability to provide informed consent or comply with study schedules or procedures.