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

On this study the following procedures are sequentially performed: eligibility determination and informed consent; cell collection by apheresis; CAR T-cell manufacturing and lymphodepleting chemotherapy all followed by CAR T-cell infusion on day 0. The first 3 subjects will be followed in hospital from day 0 until +14 for CRS, ICANS and other toxicity. The PI and two physicians not affiliated with the study (Nathan Bahary, MD, PhD and Gene Finley, MD) will review the outcome of the first three patients to assure the interim analysis meets criteria for continuing accrual. This analysis will be submitted to the IRB prior to continuing with accrual. The toxicity profile of the first three subjects will be scrutinized. Should toxicity be minimal with CRS ≤ 2 and ICANS grade ≤1 then the PI might propose modification to hospitalization between days 0 and +14 according to comparison with prior experience with commercially available product. A protocol amendment would be submitted in this case. Should no CAR T-cell related toxicity be identified on day +15, the subject will be discharged from the hospital and followed in the Medical Short Stay Unit (or designated substitute inpatient unit) daily to day 30. At the discretion of the Investigator (based upon each subject's medical condition or status), this follow-up could be reduced to thrice weekly basis (e.g. Monday-Wednesday-Friday). CAR T-cell monitoring by flow cytometry will occur on day +30 and day +100. Response will be assessed at day +30 and the subject will be discharged for outpatient follow up. Response will be assessed monthly by clinical examination to day +100 and then every 3 months to day +730. Thereafter, clinical follow up will occur every 6 months to five years and then yearly up to 15 years, or until death (whichever occurs first). All subjects treated on this study must consent to reporting of de-identified data to the Center for International Blood and Marrow Transplantation Research (CIBMTR). (See Table 1: Schedule of Study Procedures, Figure 1: Study Diagram, Table 2: Laboratory Investigation and Table 3: Response Evaluation for details of study conduct.) The clinical care of subjects enrolled on this study is entirely within the standard of care employed for patients who receive commercial product. There are no drugs, surgical procedures, radiological investigations, laboratory tests or examinations that are considered experimental except for a peripheral blood sample to detect CAR T-cells (by flow cytometry) and the actual production/manufacture of CAR T-cells occurring in the local Cell Processing Laboratory.

For this reason, the intent of this protocol is to ensure that the standard of care is strictly followed as outlined in the SOP documents, screenshots and documents included in the appendix of this document. Thus, patients receiving commercial product and those treated on this protocol should receive the same supportive care. In addition to immune effector cells, these documents often describe methods and cellular therapy products not relevant to this investigation and for our purpose these sections can be ignored.