FDA Halts Allogene Cell Therapy Trials

The U.S. Food and Drug Administration (FDA) has placed a hold on Allogene Therapeutics’ cell therapy clinical trials following a report of a chromosomal abnormality in ALLO-501A chimeric antigen receptor (CAR) T cells in a patient treated in the ALPHA2 study.

Following infusion of ALLO-501A, this patient with stage IV follicular lymphoma and C-MYC rearrangement, whose disease was refractory to two prior lines of immunochemotherapy and additional radiation therapy, experienced grade 1 cytokine release syndrome (CRS) and grade 2 immune effector cell-associated neurotoxicity syndrome (ICANS) requiring high-dose steroid therapy. Subsequently, the patient developed progressive pancytopenia, and a bone marrow biopsy showed aplastic anemia and the presence of ALLO-501A CAR T cells with the chromosomal abnormality. According to Allogene, early translational data showed that the CAR T cells expanded, peaking on day 28 before contraction. The patient experienced a partial response to ALLO-501A and underwent allogeneic stem cell transplantation.

An investigation is ongoing to further characterize the abnormality, which was detected in a bone marrow biopsy undertaken to assess pancytopenia, and identify any clinical relevance, evidence of clonal expansion, or potential relationship to gene editing.

More than 100 patients have received Allogene’s CAR T-cell products. The FDA will continue to review phase I data submitted in anticipation of a phase II trial of ALLO-501A.

Source: Allogene press release, October 7, 2021.