CAR T-Cell Clinical Trial on Hold Following Patient Death

A patient with cancer died after treatment with a gene-edited allogeneic CAR T-cell treatment.

With the historic approval of the first CAR T-cell gene therapy, it is likely that similar drugs will emerge for cancer treatment; however, there may be some serious safety concerns with this medication class.

The FDA recently placed a clinical hold on ongoing phase 1 trials of a gene-edited allogeneic CAR T-cells (UCART) treatment, UCART123, in acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN).

Cellectis, a clinical-stage biopharmaceutical company, is currently working with the FDA and clinical investigators to resume the trials using a lower dose of UCART123 to potentially mitigate serious adverse events, according to the release.

The clinical hold was initiated following the fatality of 1 patient in the BPDCN trial. This was the first patient treated with UCART123 in the trial. The patient was aged 78 years and had relapsed/refractory BPDCN with 30% blasts in his bone marrow and cutaneous lesions at baseline. This patient was previously treated.

In the study, the patient received 30-mg/m2 per day of fludarabine for 4 days and 1-g/m2 per day of cyclophosphamide for 3 days. The patient then received 6.25x105 UCART123 cells/kg, according to the release.

After 5 days, the patient experienced cytokine release syndrome (CRS) and a lung infection. These conditions were observed to improve after treatment with tocilizumab and broad-spectrum antibiotics. Cellectis reported that the patient progressed to grade 5 CRS with grade 4 capillary leak syndrome.

Despite further treatment with corticosteroids, tocilizumab and intensive care, the patient died after 9 days of receiving the treatment, according to the release.

In the AML study, the first patient treated also experienced serious adverse events, but did not result in death.

The patient was a woman aged 58 years with 85% blasts in her bone marrow. The patient received the same treatment as the patient with BPDCN.

The patient experienced CRS after 8 days, which worsened to grade 3 on day 9, but resolved by day 11 through treatment management and intensive care treatment, according to the release. The AML patient additionally experienced capillary leak syndrome, which resolved in 3 days.

The Data Safety Monitoring Board recommends that the dose of the drug be lowered to 6.25x104 UCART123 cells per kilogram in both studies and capping cyclophosphamide to a 4g dose over 3 days, according to Cellectis.