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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 该研究的假设是，在伏立诺他之前或与伏立诺他同时施用flavopiridol将阻断伏立诺他介导的p21 CIP 1诱导，减少其他抗凋亡蛋白的表达，并导致白血病细胞凋亡的广泛诱导，具有增强的治疗效果。 本研究的具体目的是：（1）确定Flavopiridol和Vorinostat联合治疗急性白血病的II期推荐剂量;（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作用;（4）观察联合用药的药效学作用;（5）观察联合给药时各药物的药代动力学;（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.