This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The hypothesis of the study is that the administration of flavopiridol prior to or concurrently with vorinostat will block vorinostat-mediated induction of p21CIP1, diminish expression of other anti-apoptotic proteins, and result in extensive induction of apoptosis of leukemic cells with enhanced therapeutic effects.
The specific aims of the study are: (1) Identify recommended phase II doses for the combination of flavopiridol and vorinostat in the treatment of acute leukemia;(2) Determine the safety, toxicities, tolerability, and maximum tolerated dose of the combination;(3) Observe clinical anti-leukemic effects of the combination;(4) Observe pharmacodynamic effects of the combination;(5) Observe the pharmacokinetics of each agent when administered in combination;(5) Observe leukemia gene expression patterns and correlate with response to treatment.
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