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First-Line Leukemia Drug Pracinostat Shows Promise in Phase II Study

Initial data indicate overall response rate of 67%

Positive results have been reported from the first stage of a two-stage, open-label phase II trial of the investigational drug candidate pracinostat (MEI Pharma) in combination with azacitidine (Vidaza, Celgene Corp.) in elderly patients with newly diagnosed acute myeloid leukemia (AML) who were unsuitable for intensive chemotherapy.

Of the first nine patients enrolled in the study, two achieved a complete response (CR) and one achieved a complete response with incomplete blood count recovery (CRi), each following one or two treatment cycles. These findings met the pre-specified CR/CRi rate required to advance to the second stage of the study. In addition, three patients achieved a partial response (PR) or a partial response with incomplete blood count recovery (PRi) after their initial or second treatment evaluation, for an overall response rate of 67%.

According to the study protocol, if three or more patients achieved a CR or a CRi among the first 27 patients, the trial will continue to enroll an additional 13 patients in the second stage, for a total of 40 evaluable patients. To date, 12 patients have been enrolled in the study. For three of these patients, it is still too early for an assessment of clinical response.

The combination of pracinostat and azacitidine has been generally well tolerated, with no new or more severe adverse events than have been previously reported, including fatigue, myelosuppresion, and gastrointestinal (GI) toxicity (i.e., nausea, vomiting, and/or diarrhea). The study’s primary endpoint is the CR/CRi rate. Secondary endpoints include the overall response rate, the complete cytogenetic/molecular response, the duration of response, progression-free survival, and overall survival.

Pracinostat is an oral histone deacetylase (HDAC) inhibitor that has been tested in several phase I and phase II clinical trials in advanced hematologic disorders and in solid tumor indications in both adult and pediatric patients. The drug has been generally well tolerated in more than 250 patients to date, with readily manageable side effects that are often associated with drugs of this class, including fatigue, myelosuppresion, and GI toxicity.

In a phase I dose-escalation trial, pracinostat showed evidence of single-agent activity in elderly patients with AML, including two out of 14 (14%) who achieved a CR, with durable responses persisting for 206+ and 362 days, respectively. In addition, results from a pilot study of pracinostat in combination with azacitidine in patients with advanced myelodysplastic syndrome (MDS) showed an overall response rate of 90% (nine out of 10), including eight patients who achieved either a CR or a CRi.

AML is the most common acute leukemia affecting adults, and its incidence is expected to increase as the population ages. The American Cancer Society estimates that approximately 14,590 new cases of AML occur each year in the U.S., with an average patient age of approximately 66 years.

Treatment options for AML have remained virtually unchanged during the past 30 years. Front-line treatment consists primarily of chemotherapy. The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology recommend azacitidine or decitabine (Dacogen, Eisai Oncology) as low-intensity treatment options for AML patients over the age of 60 who are unsuitable for induction chemotherapy.

Source: MEI Pharma; June 10, 2014.

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