ROCKET Trial Reopened Following FDA Review of Cerebral Edema Mortality

July 22, 2016

Juno Therapeutics has reopened the phase II clinical trial (ROCKET trial) of JCAR015 in adult patients with B-cell acute lymphoblastic leukemia following three deaths.

Juno Therapeutics has reopened the phase II clinical trial (ROCKET trial) of JCAR015 in adult patients with B-cell acute lymphoblastic leukemia (ALL). Following the deaths of three patients with relapsed or refractory B-cell ALL undergoing a new chimeric antigen receptor (CAR-T) therapy that caused severe cerebral edema leading to death, the US Food and Drug Administration (FDA) stepped in.

The report was recently published in the American Journal of Managed Care.

Juno quickly responded by reviewing the trial therapies and processes. The deaths occurred after fludarabine was included in the preconditioning regimen, along with cyclophosphamide. Preconditioning helps make the disease more responsive to the CAR-T treatment. Juno's president and chief executive officer, Hans Bishop, expanded further in a conference call.

“Over the past week, we have systematically reviewed multiple possible factors that could have contributed in the neurotoxicity seen on the ROCKET trial, including preconditioning, patient characteristics, toxicity management, product characteristics, and cell dose,” said Bishop.

“Although more than one factor may have contributed, based on our review of the data available, across our experience with 129 patients with ALL with cy-only and with flu-cy [fludarabine/cyclophosphamide], we believe the addition of fludarabine combined with JCAR015 was the most likely and most appropriately modifiable factor. Indeed with cy alone, the greatest number of patients treated in the ROCKET trial to date, there have not been any treatment-related deaths and the incidence of severe neurotoxicity is within the range of what we expected in light of the Memorial Sloan Kettering experience,” he added.

During ASCO's 2016 Annual Meeting, the study's research team from Memorial Sloan Kettering Cancer Center (MSKCC) concluded (abstract 7003) that potent antitumor efficacy of 19-28z CAR T cells (JCAR015) is demonstrated in adult patients with refractory or recurrent ALL regardless of pretreatment disease burden, and that patients with minimal disease appear to have more favorable toxicity profile and long-term survival rates.

“We have seen encouraging safety and efficacy results with JCAR017 and JCAR014 in adult ALL, [chronic lymphocytic leukemia, CLL], and non-Hodgkin lymphoma (NHL) patients, with as much as 70% complete response rate,” said Bishop, highlighting a need to better understand this treatment protocol in different disease types.