The U.S. Food and Drug Administration (FDA) has placed a partial clinical hold on a phase I/II trial of OXi4503, a vascular disrupting agent for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). The decision follows reports of two potential dose-limiting toxicities (DLTs) in the trial. The FDA is allowing the researchers to continue to evaluate patients in the study who are receiving a lower dose of the treatment.
The clinical trial, sponsored by Mateon Therapeutics, is evaluating the use of OXi4503 (at doses ranging from 9.76 to 12.2 mg/m2) alone and in combination with cytarabine in patients with AML or MDS.
The two reported DLTs (hypotension and acute respiratory failure) were observed at the 12.2 mg/m2 dose of OXi4503. The FDA’s hold only applies to the 12.2 mg/m2 branch of the trial, allowing researchers to continue enrollment and evaluation of patients receiving 9.76 mg/m2 of OXi4503 while the FDA reviews the 12.2 mg/m2 arm.
In the phase I trial, OXi4503 demonstrated evidence of disease response in patients with pretreated, refractory AML and those with advanced MDS. Adverse events included hypertension, bone pain, fever, anemia, thrombocytopenia, and coagulopathies.