Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced that the first patient has been enrolled in an exploratory Phase 2 clinical trial evaluating the ability of defibrotide to prevent neurotoxicity in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) receiving CAR T-cell therapy. The prospective, multicenter, open-label, single-arm study will evaluate the safety and efficacy of defibrotide in the prevention of CAR T-cell associated neurotoxicity in patients with relapsed or refractory DLBCL receiving axicabtagene ciloleucel.
“The introduction of CAR-T therapies to the oncology treatment landscape is groundbreaking but can be associated with serious complications such as neurotoxicity,” said Robert Iannone, M.D., M.S.C.E., executive vice president, research and development of Jazz Pharmaceuticals. “At Jazz, we strive to improve outcomes for patients, and we are committed through our development program to explore the potential of defibrotide, including as a preventative treatment for neurotoxicity in patients receiving CAR-T therapy.”
Patients may experience neurotoxicity after CD19 targeted CAR-T therapy,1 and while the exact cause is unknown, research suggests that endothelial cell damage may play a role.1,2 Some researchers hypothesize that the damage caused by cytokine release after CAR-T therapy may compromise the ability of endothelial cells to protect the central nervous system (CNS), causing neurotoxicity.3 This study will explore whether defibrotide could help prevent CNS endothelial cell damage, thereby protecting the CNS and minimizing neurotoxicity.
This study will be conducted in two parts, with the first part evaluating the safety of a 2.5 mg/kg/dose and a 6.25 mg/kg/dose of defibrotide based on a standard 3+3 design. Part two will evaluate the safety and efficacy of defibrotide at the recommended dose for the prevention of CAR-T-associated neurotoxicity. The primary endpoint is the incidence of CAR-T-associated neurotoxicity (any grade, defined by Common Terminology Criteria for Adverse Events [CTCAE] v5.0) by CAR-T Day +30.