Successful treatment for children and young adults with relapsed acute myeloid leukemia (AML)
continues to be a significant challenge. Despite relative improvements in survival for
patients with newly diagnosed AML, an estimated 40-60% will relapse with the majority
eventually dying of their relapsed disease. Attaining a subsequent remission in patients who
relapse is the initial critical step toward achieving a potential cure. As chemotherapy
resistance is one of the primary drivers of poor treatment response and subsequent relapse in
AML, identifying methods to reverse this resistance are desperately needed. This clinical
trial is aimed at improving the remission re-Induction rates for children and adults with
relapsed or refractory AML through epigenetic modifying agents that have the ability to
reverse chemotherapy resistance. Decitabine, a DNA methyltransferase inhibitor (DNMTi) and
Vorinostat, a histone deacetylase inhibitor (HDACi), are two epigenetic modifying drugs that
act on the methylation of proximal promoter regions of genes and on proteins involved in the
wrapping of DNA around histones, respectively. Both processes play a critical role in
regulating gene expression, and frequently these genes are involved in chemotherapy
resistance. These agents are FDA-approved for treatment in adult hematologic malignancies,
making this an opportune time to begin testing these novel therapies in pediatric leukemia
trials. This study will investigate chemotherapy priming of relapsed/refractory AML using
Decitabine and Vorinostat given for 5 days prior to standard re-Induction with Fludarabine,
Cytarabine and G-CSF for children and adults.