Phase I/II Study of 5-aza-2'-Deoxycytidine and Valproic Acid in Patients With Relapsed/Refractory Leukemia or Myelodysplastic Syndromes
Recent studies have shown synergy between demethylating agents and histone deacetylase
inhibitors. It has been shown that both DNA methylation and histone deacetylation work
together in affecting gene expression.
Therefore, drugs that inhibit DNA methylation and those that inhibit histone deacetylase can
reactivate silenced genes in combination better than they can individually. Decitabine (5
aza-2'deoxycytidine), a drug that produces marked DNA hypomethylator, has demonstrated
antileukemic activity at low doses. There are several drugs that have been shown to have
histone acetylase activity. One of these is valproic acid that has been used safely for
many years as an anti-seizure medication.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose (MTD) of Valproic Acid + Decitabine
MTD is the dose level at which less than two participants develop a dose limiting toxicity (DLT). Response evaluated after completing first cycle, 4-8 weeks of therapy.
Up to 8 weeks of therapy
Guillermo Garcia-Manero, M.D.
M.D. Anderson Cancer Center
United States: Food and Drug Administration
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