In this protocol, the investigators hypothesize that modifying the process of producing CAR+ T-cells can help to improve responses and reduce toxicities. Building on previous in vitro studies that have shown successful production of CAR+ T-cells using a new production approach, the investigators are now studying the ability to produce these CAR+ T-cells and determine how well they work in the clinical setting.
Autologous peripheral blood mononuclear cell (PBMC) will be obtained by leukapheresis over one day and the cells will be transduced with an in house designed CAR retroviral vector. Participants will receive daily intravenous (IV) infusion of lymphodepleting regimen of fludarabine and cyclophosphamide for total of 3 days (Days -5, -4, -3). The dose of cyclophosphamide will be given at 500mg/m2. The dose of fludarabine will be given at 30mg/m2. Participants will receive the CAR transduced T cells IV infusion in the BMT Inpatient Unit and remain admitted for close monitoring for at least the first 7 days following the cell infusion (D0 to Day +7), possibly longer if any side effects are encountered. The CAR transduced T cells will be escalated from 1 x 106 transduced T cells/kg (± 20%) to 2 x 106 transduced T cells/kg (± 20%) in a Phase I design, based on toxicity. Once discharged from the inpatient unit, for the next 7 days (Day +8 to Day +14) the patients will be evaluated in the High Dose Unit (labs and physical exam) to screen for toxicities.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Fludarabine is an anti-cancer drug acting as an antimetabolite that is used to treat leukemia and lymphoma cancers.
Cyclophosphamide is is an anti-cancer drug acting as an alkylating agent that is used to treat leukemia and lymphoma cancers.
CD19-CD34 CAR transduced T cells are the subject's own immune cells that target B cell markers on cancer cells.
Loyola University
Maywood, Illinois, United States
Successful production of CD19-CD34 CAR product that meet predefined release criteria (cell viability/cell number/transduction efficiency/negative sterility and viral testing) for enrolled patients
24 participants evaluated for determination of the feasibility of producing CD19-CD34 CAR T cells meeting the established release criteria
Time frame: 18 months
Adverse events
24 participants evaluated for adverse event and grading by using CTCAE v.5.0 to determine the maximal tolerated dose of CD19-CD34 CAR T cells with chemotherapy conditioning regimen for patients that have recurrent or refractory B cell malignancies
Time frame: 15 years
Response to treatment
24 participants evaluated for response to treatment by testing using PET/CT for lymphoma and using bone marrow aspirate for leukemia.
Time frame: 24 months
Progression free survival
24 participants evaluated for progression by testing using PET/CT for lymphoma and using bone marrow aspirate for leukemia.
Time frame: 24 months
Overall survival
24 participants evaluated for overall survival by clinical visit
Time frame: 15 years
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