Juno Therapeutics has voluntarily halted its Phase 2 clinical trial evaluating the investigative therapy JCAR015 in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).
The clinical hold, announced in a recent press release, was initiated after two more patients died with cerebral edema.
Seattle-based Juno notified the U.S. Food and Drug Administration (FDA) of the voluntary hold and is working with the agency and the Data and Safety Monitoring Board to determine its next steps.
This is the second setback for the Phase 2 ROCKET study, which the company placed on clinical hold in July after two patients died with similar complications. At the time, Juno executives blamed the deaths on the chemotherapy drugs used in a pre-treatment regimen rather than an effect of the experimental drug, and the FDA lifted the clinical hold a few days later.
The single-arm, multicenter ROCKET trial (NCT02535364) was designed to assess the effectiveness of Juno’s lead CAR T-cell product, JCAR015, in patients with relapsed or refractory ALL. The therapy consists of collecting a patient’s own T-cells and genetically modifying them in the lab to recognize CD19-positive cells, a protein that is widely expressed in leukemia and lymphoma cells. The cells are then expanded and re-infused into the patient’s bloodstream.
The study aimed to measure patients’ overall remission rates, including complete remission rates as its primary outcome. Secondary outcomes include duration of remission, relapse-free survival, treatment-related adverse events, and event-free survival. Overall survival is also being assessed in the trial.
In June, Juno presented updates from the Phase 1 section of the study at the American Society for Clinical Oncology (ASCO) 2016 Annual Meeting. The study had enrolled 51 patients with relapsed or refractory ALL, who received either Cytoxan (cyclophosphamide) or Fludara/Cytoxan (fludarabine/cyclophosphamide) followed by an infusion of JCAR015.
Results showed complete responses in 77 percent, or 23 of 30 patients with morphological disease burden (a more advanced stage of ALL), and 90 percent, or 18 of 20 patients with minimal disease. In patients who achieved a complete response and could be assessed for minimal residual disease, complete molecular remission was observed in 90 percent of patients with morphologic disease and 78 percent of patients with minimal disease.
After a median follow-up of 8.5 months, patients with morphologic disease had a median overall survival of nine months, while it was not reached for patients with minimal disease.
Juno’s trials and plans for its other CD19-directed CAR T-cell product candidates, including JCAR017, will not be affected by the clinical hold.