FDA Halts Phase I Trial of UCART123 in AML

Clinical trials of the allogenic gene-edited Chimeric Antigen Receptor (CAR) T-cell therapy targeting CD123, UCART123, for Acute Myeloid Leukemia (AML) patients have been placed on clinical hold by the U.S. Food and Drug Administration (FDA). UCART123 had previously been granted Investigational New Drug approval by the FDA for the treatment of AML which was reported here.

The trials have been halted after the drug manufacturer’s, Cellectis, reported the death of a patient with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) who was enrolled in the phase I ABC123 study (NCT03203369), which evaluated the safety and clinical activity of UCART123. They also reported about the first AML patient who was enrolled in the phase I AML123 study (NCT03190278), which is also evaluating the safety and clinical activity of UCART123.

The AML patient, a 58-year old woman with 84% Bone Marrow (BM) blasts, was administered 30mg/m²/day fludarabine for 4 days and 1g/m²/day cyclophosphamide for 3 days, as a preconditioning regimen. She was then administered 6.25 x 10⁵ UCART123 cells per kilogram without complication. On day 8, she experienced a grade 2 Cytokine Release Syndrome (CRS), which worsened to grade 3 on day 9 eventually leading to treatment management in intensive care unit on day 11. The patient also experienced a grade 4 capillary leak syndrome at day 9 which she recovered from on day 12.

Consequently, Cellectis have halted the clinical trials of UCART123 in AML patients and is “working closely with the investigators and the FDA in order to resume the trials” with an adjusted protocol featuring a reduced dose of UCART123. They further added that following a meeting with the Data Safety Monitoring Board on 28^th August 2017, 6.25 x 10⁴ UCART123 cells per kilogram was recommended. A total dose of 4g over 3 days of cyclophosphamide was also recommended.