The FDA has placed a clinical hold on a phase 2 trial of JCAR015 (Juno Therapeutics), a chimeric antigen receptor T-cell (CAR-T) therapy, in adults with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). The clinical hold was initiated after two patient deaths last week, which followed the recent addition of fludarabine to the preconditioning regimen.
In a conference call, a Juno executive revealed that a third trial patient had died in May. All three patients were in their 20s, and their deaths were linked to swelling in the brain, the company said.
Experimental CAR-T medications have been associated with cytokine release syndrome, a dangerous build-up of toxic debris from killed tumor cells, and with damage to healthy tissue. The inflammation is typically controlled, however, with steroids and other treatments.
Juno has proposed to the FDA that it continue the trial using JCAR015 with cyclophosphamide preconditioning alone. In response, the FDA has requested that Juno submit a revised patient informed consent form, a revised investigator brochure, a revised trial protocol, and a copy of the presentation made to the agency on July 6. Juno will submit the requested information to the FDA this week.
The single-arm, multicenter ROCKET trial is treating adult patients with relapsed or refractory B-ALL with an infusion of the patient’s own T cells that have been genetically modified to express a chimeric antigen receptor (CAR) that will bind to leukemia cells that express the CD19 protein on the cell surface. The study is designed to determine whether these modified T cells (called JCAR015) help the body’s immune system eliminate leukemia cells. The trial will also assess the safety of treatment with JCAR015; how long JCAR015 cells remain in the patient’s body; the extent to which JCAR015 eliminates minimal residual disease; and the effect of this treatment on survival. Before the clinical hold, the study’s estimated completion date was December 2017.