Phase II Randomized Double-Blinded Study of Pracinostat in Combination with Azacitidine in Patients with Untreated Higher-Risk Myelodysplastic Syndromes

BACKGROUND—The prognosis of patients with higher-risk myelodysplastic syndromes (MDS) remains poor despite available therapies. Histone deacetylase inhibitors have shown activity in MDS and in vitro synergy with azacitidine. METHODS—We conducted a phase II randomized, placebo controlled clinical trial of azacitidine and pracinostat in patients with International Prognostic Scoring System intermediate-2 or high risk MDS. Primary endpoint was complete response (CR) rate by cycle 6 of therapy. RESULTS—Of 102 patients randomized, 51 were treated in the pracinostat group and 51 in the placebo group. Median age was 69 years. CR rate by cycle 6 of therapy was 18% and 33% (p=0.07) in the pracinostat and placebo groups, respectively. No significant differences in overall survival (OS) (median 16 vs. 19 months, HR = 1.21, 95% CI 0.66–2.23) or progression-free survival (PFS) (11 vs. 9 months, HR = 0.82, 95% CI 0.546–1.46) were observed between groups. Grade ≥3 adverse events occurred more frequently in the pracinostat group (98% vs. 74%) leading to more treatment discontinuations (20% vs. 10%). CONCLUSIONS—The combination of azacitidine with pracinostat did not improve outcomes of patients with higher-risk MDS. Higher rates of treatment discontinuation may partially explain these results suggesting alternative dosing and schedules to improve tolerability may be required to determine the potential of the combination.

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