San Francisco, CA—Nearly 50% of elderly patients with newly diagnosed acute myeloid leukemia (AML) who received pracinostat, an investigational HDAC (histone deacetylase) inhibitor, in combination with azacitidine had responses in an ongoing phase 2 clinical trial.
Furthermore, “no patient who achieved a clinical response has progressed,” according to lead investigator Guillermo Garcia-Manero, MD, Chief, Section of Myelodysplastic Syndromes, Department of Leukemia, M.D. Anderson Cancer Center, Houston, and colleagues.
Previously, pracinostat demonstrated clinical evidence of single-agent activity in patients with AML and myelofibrosis. In a phase 1 dose-escalation study of 14 evaluable patients with AML, 2 patients achieved a complete response (CR)—1 lasting more than 206 days and 1 lasting more than 362 days.
Study Details
The interim phase 2 data presented at ASH 2014 come from the ongoing MEI-004 trial investigating the effectiveness and safety of the pracinostat and azacitidine combination in treatment-naïve older patients with AML.
The study is enrolling patients aged ≥65 years with newly diagnosed de novo (N = 29), secondary disease (N = 12) or treatment-related AML with intermediate- or unfavorable-risk cytogenetics and ≥20% bone marrow blasts. Overall, 80% of the patients had an ECOG performance status of 0 to 1; the remaining 20% had an ECOG status of 2.
Patients received pracinostat 60 mg orally 3 days weekly for 21 days of a 28-day cycle. Azacitidine was given subcutaneously or intravenously on days 1 to 7, or days 1 to 5 and 8 and 9 (based on site determinations) of each 28-day cycle.
The main end point is CR and full response with incomplete blood count recovery, along with morphologic leukemia-free state.
At study evaluation, 41 patients were registered at 15 centers; enrollment has been continuing since the end of 2013, and 25 patients are still active in the study. Reasons for study discontinuation included progressive disease (N = 6), adverse events (N = 6), or other (N = 4).
Interim efficacy data in 33 patients show that 45% achieved the primary end point. “Most clinical responses occur within the first 2 cycles and continue to improve with ongoing therapy,” according to the researchers. “The observed response rate may increase with longer follow-up of patients achieving partial response or stable disease.”
In addition, 3 patients had a partial response or a partial response with incomplete blood count recovery, and 4 had stable disease; 4 patients had no clinical benefit.
The most common treatment-emergent adverse events were neutropenia, febrile neutropenia, thrombocytopenia, nausea, anemia, and fatigue. Adverse events resulting in dose reductions were uncommon. Six patients have received pracinostat beyond 230 days, which attests to its long-term tolerability.
These data support definitive development of pracinostat in combination with azacitidine as treatment for older patients with AML.