FDA Grants Pracinostat Breakthrough Designation for Older Patients With AML

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/m2of 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.