Following two patient deaths last week and another earlier this year, Juno Therapeutics announced Thursday that it is putting its “ROCKET” trial on clinical hold, at the direction of the U.S. Food and Drug Administration. The patients enrolled in this Phase II trial are adults with relapsed or refractory B cell acute lymphoblastic leukemia, according to the biopharmaceutical company’s website.
Immunotherapy is heralded as the new frontier in the war on cancer. It works by helping the immune system fight the cancer. But many of these cutting-edge treatments are still in the experimentation phase. A Phase II clinical trial is designed to test the effectiveness of a new drug or treatment. It typically follows a Phase I trial, which evaluates safety and side effects. Before a new drug or treatment goes to market, it must also pass through a Phase III trial, as outlined by the National Institutes of Health.
In a conference call with reporters on Thursday, Juno CEO Hans Bishop revealed that the two patients, along with an additional patient in May, died as the result of cerebral edema — brain swelling caused by the presence of excessive fluid. Investigators, he said, pinpointed the likely culprit 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 consists of a heavy dose of chemotherapy to kill off existing cancer cells in order to give the new, cancer-killing T-cells room to grow. It’s like hitting a reset button to restart the immune system.
Fludarabine, Bishop explained, had shown to increase efficacy in previous studies, which is why the decision was made to add it to the pre-conditioning regimen in this particular trial. But an unforeseen interaction between fludarabine and the JCAR015 cells proved to be lethal.
Juno is petitioning to continue the trial with modifications, namely dropping fludarabine from pre-conditioning, in favor of a cyclophosphamide-only regimen. In turn, the FDA is asking Juno for revised protocols, consent forms and brochures, which Juno says it will submit this week.
The FDA monitors all U.S. drug trials. Fatal adverse events are “extremely rare.”
“If at any time the FDA determines that human subjects are or would be exposed to an unreasonable and significant risk of illness or injury, the FDA may place the study on ‘clinical hold,’ which prohibits further investigation until the FDA’s safety concerns are adequately addressed and the FDA removes the clinical hold order,” FDA spokesperson Tara Goodin said in an email earlier this year.