Clinical Trials

Date: 2017-08-02

Type of information: Treatment of the first patient

phase: 3

Announcement: treatment of the first patient

Company: Mei Pharma (USA - CA) Helsinn Group (Switzerland)

Product: pracinostat

Action mechanism:

• histone deacetylase inhibitor. Pracinostat is an oral histone deacetylase (HDAC) inhibitor that has been tested in a number of Phase I and Phase II clinical trials in advanced hematologic disorders and solid tumor indications in both adult and pediatric patients.
• Since August 2016, MEI Pharma has entered into an exclusive licensing, development and commercialization agreement with Helsinn for pracinostat for the treatment of acute myeloid leukemia and other potential indications.

Disease: acute myeloid leukemia (AML)

Therapeutic area: Cancer - Oncology

Country: USA

Trial details:

• This is a Phase III, multicenter, double-blind, randomized study of pracinostat vs. placebo with azacitidine (AZA) as background therapy in patients ? 18 years of age with newly diagnosed acute myeloid leukemia (AML), excluding acute promyelocytic leukemia and cytogenetic low-risk AML, who are unfit to receive intensive remission induction chemotherapy due to age ? 75 years or comorbidities.
• Patients will be randomized in a 1:1 ratio to one of two groups: Group A to receive pracinostat plus AZA and Group B to receive placebo plus AZA. Randomization will be stratified by cytogenetic risk category (intermediate vs. unfavorable-risk, according to SWOG Cytogenetic Risk Category Definitions) and ECOG performance status (0-1 vs. 2).
• Treatments will be administered based on 28-day cycles, with pracinostat/placebo administered orally once every other day, 3 times a week for 3 weeks, followed by one week of no treatment and AZA administered for 7 days of each cycle. Study treatment should continue until there is documented disease progression, relapse from complete remission (CR), or non-manageable toxicity. A minimum of 6 cycles may be required to achieve a complete remission.
• Once permanently discontinued from study treatment, patients will enter the Long-term Follow-up phase of the study and will be followed for assessment of disease progression, if applicable, and survival every 3 months (±1 month) until death. The end of this study is defined when 390 events (deaths) have occurred and the study is unblinded for final overall survival analysis. (NCT03151408)

Latest news:

• • On August 2, 2017, Helsinn and MEI Pharma announced that the first patient has been dosed in the pivotal Phase 3 study of pracinostat in combination with azacitidine in adults with newly diagnosed acute myeloid leukemia who are unfit to receive intensive induction chemotherapy. The randomized, double-blind, placebo-controlled study will enroll approximately 500 eligible patients worldwide. Patients will be randomized 1:1 to receive pracinostat or placebo with azacitidine as background therapy. The primary endpoint of the study is overall survival. Secondary endpoints include, among others, morphologic complete remission (CR) rate, event free survival (EFS) and duration of CR.
• The Phase 3 study of pracinostat in combination with azacitidine is open to adult patients with newly diagnosed AML who are unfit to receive standard induction chemotherapy due to age ? 75 years or predefined co-morbidities. Treatments will be administered based on 28-day cycles, with pracinostat or placebo administered orally once every other day, 3 times a week for 3 weeks, followed by one week of no treatment and azacitidine administered for 7 days of each cycle.
• Results from a Phase 2 open-label, single-arm, multicenter study of pracinostat and azacitidine in 50 patients aged ? 65 years with newly diagnosed AML not eligible for induction chemotherapy showed a median overall survival of 19.1 (95%CI: 10.0-26.5) months, one-year survival of 62% and a CR rate of 42%. Responses were durable (median CR+CRi 17.2 months). Blast clearance was rapid (median 8 weeks) while CR required prolonged therapy (>6 months) in some patients. The combination of pracinostat and azacitidine had no unexpected toxicities. The most common grade 3/4 treatment-emergent adverse events reported in >10% of all patients included thrombocytopenia, febrile neutropenia, neutropenia, fatigue and anemia. These results were presented at the American Society of Hematology (ASH) Annual Meeting in December 2016.

Is general: Yes