JCAR015 + cyclophosphamide

JCAR015 + cyclophosphamide is a combination therapy used primarily for the treatment of relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). JCAR015 is an autologous chimeric antigen receptor (CAR) T cell therapy in which patient T cells are genetically modified to express a CD19-specific, CD28/CD3z CAR, thereby enabling the immune cells to target and eliminate leukemia cells expressing CD19. Cyclophosphamide, a conventional alkylating agent, is used as part of the conditioning (lymphodepletion) regimen prior to infusion of the CAR T cells in order to improve the persistence and efficacy of the infused T cells. The cyclophosphamide is administered to reduce endogenous lymphocytes and enhance engraftment and expansion of the infused CAR-T cells. JCAR015 was developed by Juno Therapeutics, and this combination was studied in the phase 2 ROCKET trial. However, development was halted due to safety concerns, especially severe neurotoxicity and fatal cerebral edema associated with the regimen.