BORTEZOMIB WITH WEEKLY IDARUBICIN FOR THE TREATMENT OF AML

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。在AML患者的I期和II期临床试验中确定硼替佐米（PS-341）联合依达柔比星的安全性和有效性。这项新临床试验的基本原理是基于我们的临床前研究，证明硼替佐米和依达柔比星联合使用对原发性人AML细胞有很强的肿瘤特异性诱导凋亡。由于缺乏“标准护理”，以及由于低风险细胞遗传学、多药耐药和既往合并症的优势，这些患者的预后较差，因此老年和复发AML患者已成为本研究的目标。我们期望在I期研究中确定硼替齐米与依达柔比星联合使用时的剂量限制性毒性和最大耐受剂量；随后，该联合疗法在指定剂量下的安全性和有效性将在扩大入组的II期研究中进行探索。我们预计，通过该方案，我们将观察到有效的抗白血病活性，完全的临床缓解和更低的总体毒性。

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.