Jazz Pharmaceuticals Announces First Patient Enrolled in Phase 2 Clinical Trial Evaluating Defibrotide for the Prevention of CAR-T Associated Neurotoxicity
"The introduction of CAR-T therapies to the oncology treatment landscape is groundbreaking but can be associated with serious complications such as neurotoxicity," said
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.
Approximately 35 eligible patients will be enrolled at six medical centers across
About Defitelio® (defibrotide sodium)
In the U.S., Defitelio® (defibrotide sodium) injection 80mg/mL received U.S.
Please see full Prescribing Information for Defitelio.
▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system found under section 4.8 of the SmPC.
About CAR-T Associated Neurotoxicity
Chimeric antigen receptor (CAR) T-cell therapy is an emerging immunotherapy approach for the treatment of hematologic malignancies. 4 The two primary toxicities associated with CAR T-cell therapy include cytokine release syndrome (CRS) and neurotoxicity.4 Many patients 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 The damage caused by CAR-T therapy may compromise the ability of endothelial cells to protect the central nervous system (CNS), causing neurotoxicity.3
- Gust J, Taraseviciute A and Turtle CJ. Neurotoxicity Associated with CD19-Targeted CAR-T Cell Therapies. CNS Drugs
November 2018(32) 1091–1101.
- Santomasso BD, et al. Clinical and Biological Correlates of Neurotoxicity Associated with CAR T-cell Therapy in Patients with B-cell Acute Lymphoblastic Leukemia. Cancer Discov
August 2018(8) (8) 958-971.
- Mackall C and Miklos D. CNS Endothelial Cell Activation Emerges as a Driver of CAR T Cell–Associated Neurotoxicity. Cancer Discov
December 2017(7) (12) 1371-1373.
- Hunter BD and Jacobson CA. CAR T-Cell Associated Neurotoxicity: Mechanisms, Clinicopathologic Correlates, and Future Directions. JNCI:
Journal of the National Cancer Institute July 2019(111) (7) 646–654.
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