Epigenetic Reprogramming in Relapse AML

Phase 1 Study Number of Patients: 12 to 24 evaluable subjects will be required to enroll subjects in all 4 dose levels. Study Objectives: Primary Objectives * To determine the maximum tolerated dose (MTD) of decitabine when used in this combination with vorinostat, fludarabine, high dose cytarabine and G-CSF (FLAG) for children and young adults with relapsed or refractory AML. * To evaluate the ability to safely deliver the combination of decitabine and vorinostat followed by fludarabine, high dose cytarabine and G-CSF (FLAG) in pediatric and young adult patients with relapsed or refractory AML. Secondary Objectives o To establish the extent of hypomethylation of peripheral blood (PB) and bone marrow (BM) pre- and post- decitabine and vorinostat treatment by: LINE-1 methylation assay as a surrogate marker of global DNA methylation. Direct Comprehensive DNA methylation analysis Gene expression profiling to assess genetic changes * To analyze the correlation between DNA methylation and gene expression pre- and post-treatment with decitabine and vorinostat. * To analyze the correlation between biological changes and clinical response Selection of Study Patients: • Study entry is open to patients regardless of gender or ethnic background. While there will be every effort to seek out and include females and minority patients, the patient population is expected to be no different than that of other acute leukemia studies at the Medical College of Wisconsin.