All content on this site is intended for healthcare professionals only. By acknowledging this message and accessing the information on this website you are confirming that you are a Healthcare Professional. If you are a patient or carer, please visit the International Myeloma Foundation or Myeloma crowd.

The Multiple Myeloma Hub uses cookies on this website. They help us give you the best online experience. By continuing to use our website without changing your cookie settings, you agree to our use of cookies in accordance with our updated Cookie Policy

FDA places a clinical hold on allogeneic CAR T cell trials

Oct 15, 2021

On October 7, 2021, the U.S. Food and Drug Administration (FDA) placed a clinical hold on a series of trials investigating the use of allogeneic chimeric antigen receptor (allo-CAR) T-cell therapies for adult patients with hematologic malignancies. This was due to a safety report regarding the bone marrow biopsy of a single patient receiving the therapy in the phase I/II ALPHA2 study (NCT04416984). Results revealed the subject had aplastic anemia and ALLO-501A CAR T cells carrying a chromosomal abnormality of unclear clinical significance.1,2

The patient in whom the abnormality was detected had Stage IV follicular lymphoma with c-myc rearrangement, refractory to two previous lines of immune-chemotherapy and additional radiation treatment. Following ALLO-501A infusion, the patient experienced Grade I cytokine release syndrome and Grade II immune effector cell-associated neurotoxicity syndrome, necessitating a course of high-dose steroids. The study participant had achieved a partial response to therapy when progressive pancytopenia developed.

Previous translational data indicated the expansion of the CAR T cells, with a peak at Day 28 and contraction subsequently. The patient was unable to receive autologous CD19-targeted CAR T-cell therapy as a result of a manufacturing failure linked with an inadequate expansion of autologous CAR T cells.

The clinical hold affects five allo-CAR T cell trials for relapsed or refractory malignancies, namely the ALPHA, ALPHA2, UNIVERSAL, TRAVERSE, and IGNITE trials, which include therapies for non-Hodgkin lymphoma, multiple myeloma, and renal cell carcinoma. Prior to this incident, data from the ALPHA trials had demonstrated a favorable clinical profile of ALLO-501A. Nevertheless, clinical evaluation of the case remains ongoing, and additional details as to the immediate and underlying causes of this event are being collected, including evidence of clonal expansion or a potential relationship to the gene-editing technique used to develop the treatment.

At the same time, the U.S. FDA is reviewing end of phase I materials for a phase II pivotal trial of ALLO-501A. Supplementary updates will be provided in the coming weeks following consultation with the regulatory authorities.

About allo-CAR T cells

Allo-CAR T cells are derived from induced pluripotent stem cells from healthy donors that are genetically modified using the transcription activator-like effector nucleases gene-editing technology. Allo-CAR T cells overcome some of the manufacturing challenges of using autologous CAR T cells, reducing the timelines significantly and eliminating the need for bridging therapy. To this day, >100 patients have been dosed with these products in clinical trials.

  1. Allogene Therapeutics. Allogene Therapeutics reports FDA clinical hold of AlloCAR T trials based on a single patient case in ALPHA2 trial. Published October 7, 2021. Accessed October 13, 2021.
  2. Healio. FDA places clinical hold on Allogene’s allogeneic CAR-T trials. Published October 11, 2021. Accessed October 13, 2021.