A Phase I/II Study of LBH589 Plus Decitabine for Patients Age ≥ 60 Years With High Risk MDS or AML
To address the need for less toxic, more effective treatments for older patients with
advanced MDS and AML, the purpose of this Phase 1-2 single institution study is to evaluate
the safety and efficacy of LBH 589 and decitabine administered in combination.
Decitabine is an epigenetic modifier of gene expression that has been shown to be
well-tolerated in this population at the dose schedule proposed in this study, with
reasonable efficacy. Although its precise mechanism of action is incompletely understood, it
is postulated to work by reactivating the expression of key tumor suppressor genes silenced
in tumor cells by reversing a pattern of hypermethylation of promotor elements.
LBH389 is likewise an epigenetic modifier that inhibits the deacetylation of both histones
and non-histone proteins, including HSP90 and p53. Although clinical experience with LBH589
in AML is limited, aberrant histone deacetylase activity has been previously shown to play a
significant role in the pathogenesis of AML. The addition of LBH589 to a decitabine regimen
of previously established efficacy and tolerability will allow us to evaluate the hypothesis
that two epigenetic modifiers that are believed to work through distinct mechanisms of
action may act together to improve the responses of patients treated with decitabine alone,
without significant additional toxicity.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the maximum tolerated dose and dose limiting toxicity of LBH589 when given in combination with decitabine in patients age ≥ 60 years with high risk MDS or AML.
Approximately 3.5 years total for MTD and approximately 28 days for the DLT
Geoffrey Uy, M.D.
United States: Food and Drug Administration
08-0172 / 201012979
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