Tosedostat: Phase II ongoing

Cell Therapeutics said FDA lifted a partial clinical hold on tosedostat, which was being evaluated in 2 investigator-sponsored, open-label, U.S. Phase II trials in patients with AML or high-risk MDS. The company said it had submitted safety data to FDA from across all studies of tosedostat and that the trials were ongoing but could not enroll new patients. One trial is evaluating once-daily oral tosedostat in combination with IV cytarabine or IV decitabine on days 1-5 in 35-day cycles for up to 3 cycles in about 60 patients with newly diagnosed AML or high-risk MDS. The other trial is evaluating once-daily oral tosedostat plus subcutaneous or subcutaneous azacitidine or subcutaneous cytarabine in about 96 patients with relapsed or refractory AML or high-risk MDS.

In June, Cell Therapeutics said FDA placed a partial clinical hold on enrollment in trials of once-daily oral tosedostat after a tosedostat-treated patient died of myocarditis. Specifically, the patient received tosedostat plus either azacitidine or cytarabine in an investigator-sponsored, open-label, U.S. Phase I/II trial in patients with relapsed or refractory AML or high-risk MDS. According to the company, the agency requested additional data on the patient that died, a review of all grades of cardiac adverse events or cardiac-related investigations in tosedostat-treated patients and a benefit-risk analysis using the additional data (see BioCentury, July 1, 2013). ...