FDA Lifts Clinical Hold on Cellectis’ UCART123 Phase 1 Trials in AML, BPDCN

FDA Lifts Clinical Hold on Cellectis’ UCART123 Phase 1 Trials in AML, BPDCN

The U.S. Food and Drug Administration (FDA) has lifted a clinical hold on Cellectis‘ Phase 1 trials of UCART123 in acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN), allowing the company to resume the studies with an amended protocol.

The trials’ suspension in early September followed the death of the first patient dosed in the BPDCN trial.

UCART123 is a CAR T-cell therapy designed to target the CD123 protein found at the surface of both AML and BPDCN cells. It uses immune T-cells collected from unrelated donors that are genetically engineered to specifically target and kill CD123-positive cells.

In February 2017, the FDA approved an investigational new drug (IND) application for UCART123, making it the first allogeneic, “off-the-shelf” CAR T-cell product to enter clinical trials in the U.S.

Following this decision, Cellectar initiated the ABC123 (NCT03203369) and the AML123 (NCT03190278) studies to evaluate UCART123 in patients with BPDCN and AML, respectively.

The trials were designed to include 72 BPDCN patients and 156 AML patients who would receive a preconditioning chemotherapy regimen with fludarabine plus cyclophosphamide, followed by the CAR T-cell therapy.

The first patient enrolled in the ABC123 trial was a 78-year-old male patient with relapsed or refractory BPDCN. In the AML123 study, the first dosed patient was a 58-year-old woman with AML. They both received 625,000 UCART123 cells per kg of weight.

However, a few days after receiving the therapy, both patients experienced severe, life-threatening immune responses. While the severe medical condition of the AML patient was managed and resolved, the BPDCN patient did not respond to medical efforts and died nine days after receiving the therapy.

This led the independent Data Safety Monitoring Board (DSMB) to recommend Cellectis and trial investigators lower the dose to 62,500 UCART123 cells per kg, and reduce the cyclophosphamide dose.

In addition to these measures, Cellectar has agreed with the FDA that after the preconditioning regimen, patients must not show symptoms of uncontrolled infection or organ dysfunction.

The company has also agreed that the next three patients receiving the therapy will be under the age of 65, and that the AML123 and ABC123 studies will only include patients with at least 28 days between enrollments.

Cellectis is currently working with investigators and clinical sites to receive approvals from ethics committees for the revised protocol and to resume patient enrollment.