Phase 3 Trial of Pracinostat Plus Azacitidine Combination in AML Discontinued

A phase 3 study evaluating pracinostat in combination with azacitidine for patients with acute myeloid leukemia ineligible for standard intensive chemotherapy has been discontinued.

The phase 3 clinical trial of pracinostat in combination with azacitidine (Vidaza) as treatment of patients with acute myeloid leukemia (AML) who are ineligible for standard intensive chemotherapy has been discontinued, due its unlikeness of meeting the primary end point of overall survival (OS) announced Hilsinn and MEI Pharma, Inc.1

The decision to discontinue was influenced by interim analysis data assessed by an Independent Data Monitoring Committee.

The study demonstrated lack of efficacy, not on any safety concerns, the company announced. Depending on results further evaluating this combination, patients may be able to continue to receive pracinostat in other clinical trials.

Pracinostat, an oral histone deacetylase (HDAC) inhibitor, has previously received an Orphan Drug designation in combination with azacitidine as treatment of patients with newly diagnosed AML who are ≥75 years old or are unfit for intensive chemotherapy. The combination regimen also received a Breakthrough Therapy designation from the FDA for this indication. The European Medicines Agency has also granted an Orphan Drug designation to the combination of pracinostat plus azacitidine.

The designation from the FDA was based on the phase 2 findings published in Blood, which enrolled 50 patients with AML who were ineligible for intensive chemotherapy between December 2013 and December 2015. These patients were at least 65 years old with newly diagnosed disease.

The primary end point of the study was complete response (CR) plus CR with incomplete blood count recovery (CRi) plus morphologic leukemia-free state (MLFS). Secondary end points included OS, overall response rate, and duration of response. The median age of patients in this study was 75 years (range, 66-84), and 32 had de novo AML, 12 had secondary AML, and 5 were treatment-related. The median baseline bone marrow blast count was 40% (range, 20%-89%). Twenty patients had high-risk cytogenetics, 28 had intermediate-risk, and 2 had unknown risk.

The CR rate was 42%, and the CRi rate was 4%. The MLFS rate was 6%. The median progression-free survival was 12.6 months (95% CI, 10-17.7), and the median OS was 19.1 months (95% CI, 10-26.5). The 1-year OS rate was 62%.

The combination induced grade 3 or greater treatment-emergency adverse events in 43 patients (86%), which included infections (52%), thrombocytopenia (46%), and febrile neutropenia (44%). The 30-day all-cause mortality rate was 2%, and the 60-day rate was 10%.

The HDAC inhibitor is also under evaluation in patients with high-risk myelodysplastic syndromes in combination with various other agents, as well as azacitidine, and patients with myelofibrosis in combination with ruxolitinib (Jakafi).1


1. Helsinn group and MEI pharma discontinue the phase 3 study with pracinostat in AML after completing interim analysis. News Release. Helsinn and MEI Pharma, Inc. July 2, 2020. Accessed July 6, 2020.

2. Garcia-Manero G, Abaza Y, Takahashi K, et al. Pracinostat plus azacitidine in older patients with newly diagnosed acute myeloid leukemia: results of a phase 2 study. Blood Advances. 2019;3(4):508-519. doi:10.1182/bloodadvances.2018027409