BORTEZOMIB WITH WEEKLY IDARUBICIN FOR THE TREATMENT OF AML

该子项目是利用 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，不一定是研究者的机构。 确定硼替佐米（PS-341）联合伊达鲁肽治疗AML患者的I期和II期临床试验的安全性和有效性。这项新的临床试验的基本原理是基于我们的临床前研究，证明了使用硼替佐米和伊达洛酮的组合对原代人AML细胞的强烈肿瘤特异性细胞凋亡诱导。老年和复发性AML患者已成为本研究的目标，因为这些患者缺乏“标准治疗”，并且由于低风险细胞遗传学、多药耐药和既往合并症的优势，这些患者的结局较差。我们希望在I期研究中确定硼替佐米与依达鲁肽联合用药时的剂量限制性毒性和最大耐受剂量;随后，将在扩大招募的II期研究中探索指定剂量的联合用药的安全性和疗效。我们预期，采用该方案，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.