FDA lifts clinical hold on UCART123 trials for patients with certain hematologic malignancies

The FDA lifted the clinical hold on phase 1 trials designed to evaluate UCART123 for the treatment of acute myeloid leukemia and blastic plasmacytoid dendritic cell neoplasm, according to the drug’s manufacturer.

UCART123 (Cellectis), a gene-edited T-cell investigational drug that targets CD123, received investigational new drug approval in Feb. 2017, marking the first allogeneic, “off-the-shelf” gene-edited CAR T-cell product candidate that the FDA has approved for clinical trials, according to a company-issued release.

As HemOnc Today previously reported, the FDA placed clinical hold on all phase 1 trials on Sept. 4.

With the FDA, Cellectis agreed to revise the following protocols to be implemented in phase 1 UCART123 trials to lift the hold:

Decrease the cohort dose level to 6.25 x 10⁴ UCART123 cells/kg;
Decrease the cyclophosphamide dose of the lymphodepleting regimen to 750 mg/m² per day over 3 days with a maximum daily dose of 1.33 grams of cyclophosphamide;
Inclusion of specific criteria at day 0, the day of UCART123 infusion, including no new uncontrolled infection after receipt of lymphodepletion, afebrile, off all but replacement dose of corticosteroids, and no organ dysfunction since eligibility screening;
Provision to ensure that the next three patients to be treated in each protocol will be under the age of 65 years; and
Provision to ensure that the enrollment will be staggered across the UCART123 protocols AML123 and ABC123: at least 28 days should elapse between the enrollments of two patients across the two studies.

The company also noted it is working with the investigators and clinical sites to obtain institutional review board approvals on the revised protocols and resume patient enrollment.