FDA lifts hold on trials of universal CAR T-cell therapy

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T cells

The US Food and Drug Administration (FDA) has lifted the full clinical hold on 2 phase 1 studies of UCART123, an allogeneic chimeric antigen receptor (CAR) T-cell therapy targeting CD123.

One of these studies was designed for patients with acute myeloid leukemia (AML), and the other was designed for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN).

The hold meant no new subjects could be enrolled in either trial, and there could be no further dosing of subjects who were already enrolled.

The hold was placed in September because the first patient treated in the BPDCN trial died. The patient developed grade 2 cytokine release syndrome (CRS) and a grade 3 lung infection. This was followed by grade 4 capillary leak syndrome and grade 5 CRS.

The first patient treated in the AML trial also developed grade 4 capillary leak syndrome and grade 3 CRS, but both resolved.

Now, the FDA has lifted the hold on the trials because Cellectis, the company developing UCART123, agreed to implement the following main revisions to phase 1 UCART123 protocols:

• Decrease the cohort dose level to 6.25 x 10⁴ UCART123 cells/kg
• Decrease the cyclophosphamide dose of the lymphodepleting regimen to 750 mg/m²/day over 3 days, with a maximum daily dose of 1.33 grams
• Include specific criteria at Day 0, the day of UCART123 infusion, such as no new uncontrolled infection after receipt of lymphodepletion, afebrile, off all but replacement dose of corticosteroids, and no organ dysfunction since eligibility screening
• Ensure the next 3 patients to be treated in each protocol will be under the age of 65
• Ensure that enrollment will be staggered across the UCART123 protocols; at least 28 days should elapse between the enrollments of 2 patients across the 2 studies.

Cellectis is currently working with investigators and clinical sites to obtain internal review board approval on the revised protocols and resume patient enrollment.