FDA Places Clinical Hold on Studies of Allogeneic CAR T-Cell Therapy

The U.S. Food and Drug Administration (FDA) has placed a clinical hold on two phase I trials of gene-edited allogeneic chimeric antigen receptor (CAR) T cells (UCART123) in patients with acute myeloid leukemia (AML) or blastic plasmacytoid dendritic cell neoplasm (BPDCN), after the therapy’s manufacturer, Cellectis, reported a patient death in the BPDCN trial.

The man who died, a 78 year old with relapsed/refractory BPDCN with 30 percent bone marrow blasts, was the first patient treated in the BPDCN study. After receiving a conditioning regimen of fludarabine and cyclophosphamide, the patient received UCART123 6.25×105 cells/kg, without complication, but he experienced grade 2 cytokine release syndrome (CRS) and grade 3 lung infection on the fifth day of treatment. Despite CRS management with tocilizumab, he died on the ninth day of treatment.

The Data Safety Monitoring Board recommended lowering the UCART123 dose to 6.25×104 cells/kg and capping cyclophosphamide to a total dose of 4 g/m2 over three days. Cellectis stated that it will work with the investigators and the FDA to safely resume the trials with an amended protocol.

Source: Cellectis press release, September 4, 2017.