Allogene announced that the chromosomal abnormality was not detected in any manufactured AlloCAR T product or any patient treated with the same lot of drugs.
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The U.S. Food and Drug Administration lifted the clinical hold on all of Allogene Therapeutics’ AlloCAR T clinical trials. The regulatory agency first placed the hold on the company’s programs following the discovery of a chromosomal abnormality in an advanced cancer patient who had been treated with ALLO-501A.
In its announcement this morning, Bay Area-based Allogene said investigations determined that the chromosomal abnormality was unrelated to TALEN gene editing or Allogene’s manufacturing process and had no clinical significance. Additionally, Allogene announced that the chromosomal abnormality was not detected in any manufactured AlloCAR T product or any patient treated with the same lot of drugs.
“The abnormality occurred in the patient after the cell product was administered. It involved regions of the T cell receptor and immunoglobulin genes known to undergo rearrangement as part of the T cell or B cell maturation process,” Allogene said in its announcement.
The clinical hold was placed on all five of the company’s AlloCAR T trials after a patient participating in the ALPHA2 study displayed the abnormality. That patient had received ALLO-501A as a potential treatment of Stage IV transformed follicular lymphoma and c-myc rearrangement. ALLO-501A is a next generation engineered anti-CD19 AlloCAR T candidate.
After the patient had been infused with ALLO-501A, a bone marrow biopsy was undertaken to assess pancytopenia (low blood counts), which is when the chromosomal abnormality was discovered. At the time, Allogene had already dosed more than 100 patients with its AlloCAR T products.
Rafael Amado, head of research and development and chief medical officer of Allogene, expressed thanks to the FDA and its clinical partners for the support over the past few months while the hold has been investigated.
“Allogeneic CAR T therapy is a rapidly developing field that continues to evolve both in scope and impact, and the findings from our investigation will help advance innovation in the fields of gene editing and cell and gene therapy. As the leading developer of allogeneic cell products, we look forward to resuming our clinical trials as we work to fulfill our commitment to bring patients the first allogeneic CAR T product,” Amado said in a statement.
Following the lift, Allogene said it is working with clinical trial investigators to resume the ALPHA2 study and the other AlloCAR T programs as quickly as possible. Pending discussions with the FDA, the company plans to initiate a pivotal Phase II trial of ALLO-501A in relapsed/refractory Large B Cell Lymphoma later this year.
