US FDA lifts hold on Vion’s Cloretazine trial

PRLog (Press Release) – Jan 09, 2008 – The US Food and Drug Administration has lifted its clinical hold on Vion Pharmaceuticals’ Phase III trial of its lead anti-cancer agent, Cloretazine (VNP40101M), in combination with Ara-C (cytarabine) in relapsed acute myelogenous leukaemia (AML).


The company suspended enrolment and further patient treatment in the double-blind placebo-controlled study, CLI-037, in May 2007, pending a medical review of all data from the trial - a randomised evaluation of Ara-C plus Cloretazine compared with Ara-C and placebo. The suspension was recommended by the trial’s Data Safety Monitoring Board after an interim analysis of data from the first 210 treated patients, from which it concluded that any advantage in complete remission could be compromised by the observed mortality to date.


The study remained blinded overall, while a review was conducted by Vion’s medical consultants and external independent reviewers. They concluded that the combined myelosuppressive effects of Cloretazine and cytarabine at the dose and schedule used in the trial, in conjunction with the poor haematologic reserve of patients with relapsed AML, were major factors in the difference in mortality seen between the Cloretazine- and placebo-treated groups. A review of records from patients who died did not suggest any previously unreported toxicity for Cloretazine or cytarabine.


There was an increase in the response rate observed for patients treated with Cloretazine and cytarabine compared with those treated with cytarabine and placebo, despite the difference in deaths between the two groups.


An agreement has been reached with the FDA on modifications to the study, including a lower dose of Cloretazine as well as prophylactic therapy with antibiotics, antifungals and growth factors for all patients. The company is required to submit a modified Special Protocol Assessment to the FDA before the trial restarts.


Lead investigator Dr Frank Giles, chief of the division of haematology and medical oncology at the University of Texas Health Science Center at San Antonio, commented: “Cloretazine has recently shown very significant single-agent activity in the difficult-to-treat elderly AML patient population.” Vion is evaluating Cloretazine as a single agent in a pivotal Phase II trial in elderly patients with de novo poor-risk AML at 20 sites in the US and Europe. Preliminary data were presented at the American Society of Hematology annual meeting in December 2007, and the company plans to file a New Drug Application with the FDA this year.


“It is important that we now establish the optimal dosing schedule in combination with other chemotherapeutic agents, such as cytarabine. 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,” Dr Giles added. Vion plans to file an abstract based on data from study CLI-037 at the American Society of Clinical Oncology annual meeting in June 2008.


Cloretazine is a unique alkylating agent. It is also being evaluated in clinical trials as a single agent in small cell lung cancer, with temozolomide in brain tumours, and with stem cell transplantation in advanced haematologic malignancies. Article submitted by www.jobs4dd.com - for latest news and jobs on the clinical research industry.