The U.S. Food and Drug Administration lifted the clinical hold on two phase I trials of Cellectis’ UCART123, its gene-edited allogeneic chimeric antigen receptor (CAR) T-cell products for the treatment of acute myeloid leukemia and blastic plasmacytoid dendritic cell neoplasm (BPDCN). The trials were halted on September 4, after the manufacturer reported a patient death in the BPDCN trial.
The hold was lifted after Cellectis agreed to the following protocol revisions:
- decrease the cohort dose level to 6.25×104 UCART123 cells/kg
- decrease the cyclophosphamide dose of the lymphodepleting regimen to 750 mg/m²/day over three days with a maximum daily dose of 1.33 grams of cyclophosphamide
- include specific criteria at the day of UCART123 infusion, such as no new uncontrolled infection after receipt of lymphodepletion, afebrile, off all but replacement dose of corticosteroids, and no organ dysfunction since eligibility screening
- ensure that the next three patients in each study will be under the age of 65 years
- stagger enrollments: at least 28 days should elapse between the enrollments of two patients across the two studies
Source: Cellectis news release, November 6, 2017.