BORTEZOMIB WITH WEEKLY IDARUBICIN FOR THE TREATMENT OF AML

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。目的：在急性髓细胞白血病(AML)患者的I期和II期临床试验中，确定波特佐米(PS-341)联合伊达比星的安全性和有效性。这项新的临床试验的基本原理是基于我们的临床前研究，该研究表明，使用Bortezomib和伊达比星的组合对原代人类AML细胞具有很强的肿瘤特异性诱导凋亡作用。老年和复发的急性髓细胞白血病患者是这项研究的目标，因为缺乏“护理标准”，并且由于低风险细胞遗传学、多药耐药和既往并存的优势，这些患者的预后很差。我们希望在第一阶段研究中确定硼替吉米与伊达比星联合使用时的剂量限制毒性和最大耐受量；随后，将在扩大登记的第二阶段研究中探索指定剂量联合的安全性和有效性。我们预计，通过这种方案，我们将观察到强大的抗白血病活性、完全临床缓解和较少的整体毒性。

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. To determine safety and efficacy of bortezomib (PS-341) in combination with idarubicin in a phase I and II clinical trial for patients with AML. The rationale for this novel clinical trial is based on our preclinical studies demonstrating a strong tumor-specific induction of apoptosis for primary human AML cells using the combination of bortezomib and idarubicin. Elderly and relapsed AML patients have been targeted for this study due to the lack of a "standard of care" and poor outcomes for these patients owing to a preponderance of poor-risk cytogenetics, multi-drug resistance, and antecedent co-morbidities. We expect to define dose-limiting toxicities and a maximal tolerated dose of bortezimib when combined with idarubicin in a phase I study; subsequently, safety and efficacy of the combination at the designated dose will be explored in a phase II study with expanded enrollment. We anticipate that with this regimen we will observe potent anti-leukemia activity, complete clinical remissions and less overall toxicity.