While this trial remains blinded overall, a portion of data on 210 patients was unblinded for review at interim analysis. The company’s medical consultants and external independent reviewers performed a comprehensive safety analysis of Vion Study CLI-037. This analysis concluded that the combined myelosuppressive effects of Cloretazine (VNP40101M) and cytarabine given at the dose and schedule at which they were combined in the trial, in conjunction with the poor hematologic reserve of patients with relapsed acute myelogenous leukemia (AML), were major factors in the difference in mortality seen between the two arms of the study.
There was an increase in the response rate observed on the Cloretazine (VNP40101M) and cytarabine arm of the trial relative to the cytarabine and placebo arm, despite the difference in deaths between the two arms. An agreement has been reached with the FDA on modifications to Vion Study CLI-037. The revised study includes a lower dose of Cloretazine (VNP40101M) in the experimental arm of the trial and prophylactic therapy with antibiotics, antifungals and growth factors for all patients. In order to maintain the special protocol assessment (SPA) with the FDA for this trial, the next step is to submit an SPA to the FDA with these modifications before recommencing the trial.
Frank Giles, lead investigator on the Cloretazine clinical program, said: “Modifications to this Phase III trial in patients with relapsed AML will allow us to examine a combination schedule that should maintain the activity observed in the initial portion of the study with an acceptable marrow toxicity profile.”