The U.S. Food and Drug Administration (FDA) granted breakthrough therapy designation for pracinostat in combination with azacitidine for patients with newly diagnosed acute myeloid leukemia (AML) who are ≥75 years old or ineligible for intensive chemotherapy.
The FDA’s decision was based on the results of a phase II trial that reported a complete response rate (primary endpoint) of 42 percent and a median overall survival (secondary endpoint) of 19.1 months among treatment-naïve older AML patients treated with pracinostat and azacitidine.
A total of 50 patients were enrolled at 15 study locations between December 2013 and December 2015. The median patient age was 75 years (range = 66-84 years), and at baseline, the median bone marrow blast count was 40 percent (range = 20-89%).
Patients received 28-day cycles of the following regimen until disease progression, unacceptable toxicity, or no response:
- 60 mg of oral pracinostat administered on three alternating days each week for three weeks
- 75 mg/m2 of azacitidine administered intravenously or subcutaneous on days one through seven or one through five and eight through nine
The most common treatment-related grade ≥3 adverse events (AEs) included febrile neutropenia (30%), thrombocytopenia (22%), neutropenia (10%), cellulitis (10%), anemia (8%), fatigue (8%), sepsis (6%), and pancytopenia (6%). Seven patients experienced AEs that led to treatment discontinuation, including peripheral motor neuropathy (n=1), parainfluenza (n=1), atrial fibrillation/prolonged QTc (n=1), subdural hematoma after a fall (n=1), and sepsis (n=3).
Source: FDA news release, August 1, 2016.