CLINICAL TRIAL: PHASE I TRIAL OF VORINOSTAT (SAHA) IN COMBINATION WITH FLAVOPIRI

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 该研究的假设是，在伏立诺他之前或同时服用黄吡醇将阻断伏立诺他介导的 p21CIP1 诱导，减少其他抗凋亡蛋白的表达，并导致广泛诱导白血病细胞凋亡，从而增强治疗效果。 该研究的具体目的是：（1）确定黄吡醇和伏立诺他联合治疗急性白血病的推荐II期剂量； (2)确定联合用药的安全性、毒性、耐受性和最大耐受剂量； (3)观察联合用药的临床抗白血病效果； (4)观察联合用药的药效作用； (5)观察各药物联合用药时的药代动力学； (5)观察白血病基因表达模式并与治疗反应相关。

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.