Juno Therapeutics announced that the U.S. Food and Drug Administration (FDA) has placed a clinical hold on the Phase 2 ROCKET clinical trial of JCAR015 in adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r ALL).
The clinical hold was ordered after two patients recently died after the introduction of fludarabine to the preconditioning regimen.
The single-arm, multicenter Phase 2 trial was designed to treat adult patients with r/r ALL with an infusion of the patient’s own T-cells that had been genetically modified to express a chimeric antigen receptor (CAR) binding to leukemia cells that express the CD19 protein on the cell surface.
The study aimed to determine whether these modified T-cells (JCAR015) help the body’s immune system fight leukemia cells. Other objectives of the trial included assessing treatment safety, duration of JCAR015 cell life, the extent to which JCAR015 eliminated minimal residual disease, and the impacts of this treatment on patient survival.
Juno proposed the U.S. FDA allow the ROCKET clinical trial continue using JCAR015 with cyclophosphamide preconditioning alone. The FDA responded, requesting that Juno re-submit, as a complete response to the clinical hold:
- A revised patient informed consent form;
- A revised investigator brochure;
- A revised trial protocol;
- A copy of the presentation made to the FDA upon the request.
Juno has committed to responding to the FDA with all the requested information. According to a press release, the company will continue to develop multiple cell-based product candidates aimed at treating B-cell malignancies, as well as solid tumors.
To date, several products have reportedly shown promising responses in clinical trials in refractory leukemia and lymphoma. The company’s long-term goal is to leverage its cell-based platform to develop new product candidates that address a broader range of cancers and human illnesses. No other CD19-directed CAR-T-cell product candidates, including JCAR017, were affected by the FDA’s decision.
