FDA Halts Cancer Trial After Deaths
The US Food and Drug Administration has ordered Juno Therapeutics to suspend its Phase II immunotherapy trials with adult patients suffering from relapsed or refractory B cell acute lymphoblastic leukemia after the biopharmaceutical company confirmed that three of its participants have died.
Juno’s CEO, Hans Bishop, said the three patients died as the result of cerebral edema, brain swelling caused by the presence of excessive fluid. One of the deaths occurred in May, the other two on a more recent, unspecified, date.
The company said investigators believe the cause most likely to have been to be the addition of fludarabine to the pre-conditioning regimen, a one-time primer for treatment. In this particular course of treatment, pre-conditioning consisted of a heavy dose of chemotherapy to kill off existing cancer cells and thus give the new, cancer-killing T-cells room to grow.
In a conference call with US media, Bishop said fludarabine had been shown to increase efficacy in previous studies, which is why it was added to the pre-conditioning regimen in this trial. However, he said, an “unforeseen interaction” between fludarabine and the JCAR015 cells proved to be lethal.
Juno said it was submitting revised protocols, consent forms and brochures to the FDA, as requested, and petitioning the agency to continue the trial with modifications, in particular dropping fludarabine from pre-conditioning in favor of a cyclophosphamide-only regimen.
Safety in clinical is coming increasingly under scrutiny in the wake of recent fatalities. In France, the health ministry has presented a plan to tighten rules governing human drug trials an incident in Rennes in January led to the death of one volunteer and left five others in serious or critical condition.
The French incident, called the worst of its kind ever in the country, led to the suspension of tests with the medication manufactured by Portugal’s Bial and designed to treat Alzheimer’s and Parkinson’s diseases.
