This is an open label, non-randomized, phase 1 study of anti-CD19 CAR-T cells against relapsed CD19 positive NHL, CLL and ALL based in a lymphodepletion regimen (fludarabine and cyclophosphamide) and using a CellReGen-based process for manufacturing CAR-T cells.
This study will utilize a staggered enrollment design with a safety observation period.
Subjects aged ≥ 18 years.
Histologically confirmed relapsed or refractory CD-19+ malignancy, including: non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia (ALL), Chronic Lymphocytic Leukemia (CLL)/Richter's syndrome, primary CNS lymphoma. CD-19+ must be confirmed by immunohistochemistry or flow cytometry analysis.
Subjects who are relapsed or refractory to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy.
ECOG Performance Status ≤ 2.
Autologous or allogeneic stem cell transplant or CAR-T therapy within 6 weeks of planned CAR-T cell infusion.
Subjects with active infection that requires systemic treatment
History of autoimmune disease (i.e. rheumatoid arthritis, systemic lupus erythematosus) with requirement of immunosuppressive medication within 6 months.
Pregnant or breastfeeding women are excluded from this study because CAR-T cell therapy may be associated with the potential for teratogenic or abortifacient effects. Women of child bearing potential must have a negative serum pregnancy test. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with CAR-T cells, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study.
Single group
Anti-CD19 CAR-T cells
Biological/VaccineAnti-CD19 CAR-T cells are autologous T cells, engineered to express an extracellular single chain variable fragment (scFv) derived from a murine anti-human CD19 hybridoma clone FMC63 linked in frame to hinge region derived from human CD8, transmembrane domain derived from Tumor Necrosis Factor Receptor Super Family 19 (TNFRSF19) the transactivation costimulatory domain 4-1BB, and CD3 zeta signaling domain (Miltenyi Biotec Inc). Anti-CD19 CAR-T cells will be cryopreserved in infusible cryomedia for a later infusion. Anti-CD19 CAR-T cells will be administered in 1 to 3 bags. Bag aliquoting, cell content and cryomedia composition will be done according to specifications in the CMC.
Production and infusion of CAR-T therapy in 5/6 patients who have undergone successful apheresis and no more than 3/6 patients with ≥ grade 3 non-hematological CAR-T related toxicities or events of special interest within 28 days of CAR-T administration.
To assess the feasibility of administering CAR-T cells targeting CD19 for the treatment of relapsed/refractory B cell lymphomas, relapsed/refractory chronic lymphocytic leukemia (CLL), Richter's Syndrome, or relapsed/refractory acute lymphoblastic leukemia (ALL). Feasibility is defined as production and infusion of CAR-T therapy in 5/6 patients who have undergone successful apheresis and no more than 3/6 patients with ≥ grade 3 non-hematological CAR-T related toxicities or Events of Special Interest within 28 days of CAR-T administration.
Objective response rate (ORR) defined as the proportion of subjects achieving a confirmed PR or CR at Day 28 and Month 3.
To assess the objective response rates (ORR) of subjects who have received anti-CD19 CAR-T cells
Disease free survival at 1 year post CAR-T administration based on 2014 Lugano Criteria (NHL patients) , IWCLL criteria (CLL patients) or EWALL recommendations (ALL patients).
To assess disease-free survival (DFS)
Overall survival as defined as the time from CAR-T administration until 6 months and 12 months post CAR-T administration
To assess overall survival (OS)
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University of Utah
Lead sponsor
Lentigen Technology, Inc.
Collaborator
Huntsman Cancer Institute
Collaborator
