This is a single-center, nonrandomized, open-label dose-escalation study followed by dose-expansion of CD19- CD34t metabolically programmed CAR T-cell therapy in adult patients with relapsed or refractory CD19 B-cell non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).
Disease Related Criteria
CD19+ aggressive non-Hodgkin lymphoma including any of the following subtypes
Diffuse Large B-cell Lymphoma, not otherwise specified
DLBCL, germinal-center B-cell type (GCB)
Prior/Concurrent Therapy Related Criteria Guidelines regarding when lymphoma directed therapy should be stopped prior to leukapheresis, lymphodepleting chemotherapy, and CAR T-cell infusion are detailed in the protocol. These criteria must be planned to be met for all patients.
Clinical/Laboratory Criteria
Women who are pregnant or breast-feeding.
Participants with active CNS lymphoma. Participants can have a history of active CNS lymphoma as outline in protocol
Sequential
Cyclophosphamide injection
Drug500 mg/m2 IV over 30-60 minutes +/- 10 minutes before Fludarabine Days -5, -4, - 3
Fludarabine Injection
Drug30 mg/m2 IV over 30-60 minutes +/- 10 minutes after cyclo- phosphamide infusion Days -5, 4, -3
CD19-CD34t metabolically programmed CAR transduced T-cells
Biological/VaccineCells are to be infused intravenously (IV) over 30 minutes or less via nonfiltered tubing either by gravity or a peristaltic pump, gently agitating the bag during infusion to prevent cell clumping
MTD/MAD/RP2D evaluation
Maximum tolerated dose (MTD), maximum administered dose (MAD) and the recommended phase 2 dose (RP2D) of CD19-CD34t metabolically programmed CAR T-cells
CRS occurrence evaluation
Rate of grade 3 or higher cytokine release syndrome(CRS)
ICANS occurrence evaluation
rate of grade 3 or higher immune effector cell-associated neurotoxicity syndrome (ICANS)
Overall response and complete remission rate
1\. Anti-tumor activity of CD19-CD34t metabolically programmed CAR T-cell therapy in adult patients with relapsed or refractory CD19 B-cell NHL or CLL/SLL based on overall response rate (ORR) and complete remission (CR) rate. The response rate for patients with NHL will be determined by the 2014 Lugano IWG criteria. The response rate for CLL/SLL patients will be determined by the 2018 iwCLL criteria
Progression free survival, duration of response, overall survival evaluations
Anti-tumor activity of CD19-CD34t metabolically programmed CAR T-cell therapy in adult patients with relapsed or refractory CD19 B-cell NHL or CLL/SLL based on progression free survival (PFS), duration of response (DOR), and overall survival (OS)
ORR and CR evaluation at the RP2D
Anti-tumor activity of CD19-CD34t metabolically programmed CAR T-cell therapy in adult patients with relapsed or refractory CD19 B-cell NHL or CLL/SLL treated at the RP2D based on ORR and CR rate. The response rate for patients with NHL will be determined by the 2014 Lugano IWG criteria. The response rate for CLL/SLL patients will be determined by the 2018 iwCLL criteria
PFS, DOR and OS evaluation at the RP2D
Anti-tumor activity of CD19-CD34t metabolically programmed CAR T-cell therapy in adult patients with relapsed or refractory CD19 B-cell NHL or CLL/SLL treated at the RP2D based on PFS, DOR and OS.
Click on the lead sponsor to view all of their trials.
