MethylGene has begun the first of several Phase I/II clinical trials that will evaluate the combination therapy using MGCD0103 and azacitidine (Vidaza) in patients with advanced myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML).

MGCD0103 is a rationally designed, oral, isotypic-selective, small molecule inhibitor of histone deacetylases (HDACs). HDACs are enzymes that are believed to play a role in cancer progression. Aberrant DNA methylation is also believed to play a role in cancer. Vidaza, a demethylating agent, is a first-line monotherapy treatment for MDS. HDAC inhibitors, such as MGCD0103, and demethylating agents both act by turning on tumor suppressor genes that have been inappropriately turned off. Tumor-suppressor genes are the body's natural defense against cancer. Preclinical studies demonstrate that MGCD0103 and demethylating agents synergistically kill cancer cells.

In the Phase I portion of the trial, MGCD0103 will be given orally, three times per week in combination with standard Vidaza treatment. Key objectives of this portion of the study will be to evaluate the compatibility and safety of administering these two agents together, and to determine the maximum dose of MGCD0103 that can safely be administered in this combination. Secondary objectives include determining the dose-limiting toxicities, the objective responses to MGCD0103 and Vidaza, and measuring the pharmacodynamic and pharmacokinetic effects. In the Phase II portion of the trial, the purpose will be to determine the overall response rate. The trial is expected to enroll up to 50 patients at five sites at leading cancer centers in North America.