CuraGen and TopoTarget start leukemia treatment trial

The trial is being conducted at multiple sites in the European Union.

Patients under the age of 60 with relapsed or refractory acute myeloid leukemia (AML), or patients over 60 with newly diagnosed or previously treated AML, are eligible for enrollment in the trial.

Initially, 24 to 40 patients will be enrolled into one of two treatment arms and receive intravenous treatment with a combination of belinostat and idarubicin, an anthracycline. Patients will receive standard doses of idarubicin in combination with either belinostat administered intravenously once daily for five days, or a continuous infusion of belinostat over 24 to 48 hours.

Enrollment into the arms will occur in parallel in order to assess safety and define the maximum tolerated dose (MTD) for each treatment regimen. Upon establishing the MTD for each treatment arm, the trial will be advanced into Phase II to further define the safety and efficacy of belinostat in combination with standard doses of idarubicin.

Patients demonstrating complete or partial response will continue to receive treatment with belinostat until disease progression. The primary objectives for the study include safety, tolerability, and efficacy for each treatment regimen. Secondary objectives include time to response, duration of response, and survival.

The trial will also include pharmacokinetic and pharmacodynamic studies to evaluate the inhibition of histone deacetylase (HDAC) enzymes in AML cells from patients treated with belinostat. Evaluation of the genes regulating proliferation and apoptosis (programmed cell death) and the differential gene expression in AML cells obtained both prior to and following treatment with belinostat will also be performed.

In preclinical studies, belinostat has shown potent growth-inhibitory activity on leukemic cell lines, and there is evidence that belinostat has an additive effect when combined with anthracyclines, according to the companies.