US FDA tells Cellectis to halt cell therapy trials after patient death
Cellectis announced the clinical hold yesterday, explaining it applied to both Phase I studies – known as ABC123 and AML123 - in which the therapy is being examined.
The deceased man - a 78 year old in the ABC study who was suffering with relapsed blastic plasmacytoid dendritic cell neoplasm (BPDCN) – died nine days after receiving the first dose of UCART123.
According to Cellectis, after a preconditioning regimen involving fludarabine and cyclophosphamide, the patient was treated with UCART123 on August 16.
Five days later he experienced a grade 2 Cytokine Release Syndrome (CRS) and a grade 3 lung infection which improved after treatment with tocilizumab and antibiotics.
However, at day eight the patient experienced a grade 5 CRS event and grade 4 Capillary Leak Syndrome that did not respond to corticosteroids and tociluzumab. He died the following day.
Cellectis also revealed the first patient treated in the AML study, a 58-year old woman suffering acute myeloid leukemia who received the same preconditioning regimen and the same dose of UCART123, had recoveered after experiencing similar complications.
According to the firm “She experienced an initial grade 2 CRS at Day 8, worsening to a grade 3 at Day 9 and resolving at Day 11 with treatment management in intensive care unit. She also experienced a grade 4 Capillary Leak Syndrome at Day 9, resolved at Day 12.”
Cellectis said it is “working closely with the investigators and the FDA in order to resume the trials with an amended protocol including a lowered dosing of UCART123.”
UCART123 consists of T-cells modified to target the CD123 antigen on the surface of cancerous cells.
The therapy – which is made on Cellectis behalf by the LFB Group subsidiary CELLforCURE - is produced using Talen gene editing to insert genes that encode a chimeric antigen receptor (CAR) that targets the CD123 antigen.
Unlike autologous cell therapies made from the specific patients’ own cells, UCART123 is composed of lymphocytes harvested from an unrelated, so called “universal” donor.
According to Cellectis, Talen gene editing prevents the T-cells from interacting with non-target proteins, thereby reducing side-effects
The US Food and Drug Administration (FDA) cleared Cellectis to start trialling UCART123 in February.