Cellectis’ work on an off-the-shelf CAR-T therapy was placed on hold by the United States Food and Drug Administration following the death of one of the patients enrolled in the company’s clinical trial for the therapy.
The French biopharmaceutical firm is now working closely with the investigators and the FDA in order to resume the trials with an amended protocol including a lowered dosing of UCART123, according to a statement released by the company.
The hold was placed on both UCART123 ongoing Phase 1 studies, respectively in acute myeloid leukemia (AML) and in blastic plasmacytoid dendritic cell neoplasm (BPDCN).
A 78-year-old BPDCN male patient received a dose of CD123-targeting CAR-T UCART 123 on August 16. Nine days later, the patient died.
The man was the first patient treated in the BPDCN study. Initially, he was given the lowest UCART123 does without any complications.
On the fifth day, he experiences a grade 2 cytokine relapse syndrome (CRS), and a grade 3 lung infection. The patient’s condition “quickly improved” after a dose of tocilizumab and an injection of a broad spectrum antibiotic.
“Despite a treatment in keeping with CRS management including administration of corticosteroid and tocilizumab x 2 as well as intensive care unit support, the patient died on Day 9,” the press release from Cellectis said.
Another patient treated in the study experienced a similar but less severe reaction. The 58-year-old woman with AML was given the same dose of UCART 123 as the BPDCN patient.
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 which was resolved at Day 12, the company said.
CAR-T therapy is a groundbreaking new method for treating a number of conditions.
Earlier this month, the FDA gave the green light to Novartis’ CAR-T therapy which uses a patient’s own immune cells to destroy aggressive blood cancer cells. With this method, the patient’s T-cells are collected and sent to a manufacturing centre where they are genetically modified to include a new gene that contains a specific protein (a chimeric antigen receptor or CAR) that directs the T-cells to target and kill leukemia cells that have a specific antigen (CD19) on the surface.
Cellectis now has to determine what precautions to take before moving forward with enrolling more BPDCN and AML patients for the two phase 1 trials it plans.
So far the DSMB (Data Safety Monitoring Board) met on August 28 and recommended lowering the dose to 6.25×10 UCART123 cells per kilogram in both studies and capping cyclophosphamide to a total dose of 4g over 3 days.