ZOSUQUIDAR TRIHYDROCHLORIDE DURING CONVENTIONAL INDUCTION AND POST-REMISSION

常规诱导和缓解后期间的 ZOSUQUIDAR 三盐酸盐

• 批准号: 7379079
• 负责人: LARRY D CRIPE
• 金额: $ 0.04万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7379079
• 关键词: ZOSUQUIDAR; TRIHYDROCHLORIDE; DURING; CONVENTIONAL; INDUCTION

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 remission rate and median overall survival of older adults (defined as age greater than 55 to 60 years of age) who are treated for newly diagnosed acute myeloid leukemia (AML) is approximately 50% and 12 months respectively. The primary reason for the poor prognosis is chemotherapy resistance. A very well characterized mechanism of chemotherapy resistance is the active efflux of drug medicated by the multdrug resistance protein (MDR1). The expression of MDR1 correlates with a reduced remission rate and median overall survival. Therefore, inhibition of MDR1 mediated efflux may improve treatment outcome. Zosuquidar trihydrochloride (LY335979) is a specific and potent modulator of MDR1-mediated efflux. Furthermore, it has minimal pharmacokinetic interactions with daunorubicin, an essential drug in the treatment of AML. The current clinical trial requires the collection and preservation of plasma samples for pharmacokinetic analysis of daunorubicin and cytarabine in the presence of placebo or Zosuquidar. The support of the GCRC is requested to process the samples of whole blood. Patients will not receive protocol therapy on the GCRC. Patients with newly diagnosed AML or advanced MDS will be admitted to the protected environment rooms of 5N University Hospital. Patients will receive conventional induction chemotherapy (three doses of daunorubicin given daily and continuous infusion of cytarabine) in addition to either placebo or zosuquidar for six hours daily with each dose of daunorubicin. Patients will have blood samples obtained for pharmacokinetic analysis of daunorubicin and cytarabine immediately prior to the third dose of daunorubicin and for the next four days (six samples).

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。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。所列机构为中心机构，不一定为研究者机构。新诊断的急性髓性白血病（AML）治疗的老年人（定义为年龄大于55至60岁）的缓解率和中位总生存期分别约为50%和12个月。预后不良的主要原因是化疗耐药。化疗耐药的一个非常好的表征机制是由多药耐药蛋白（MDR 1）介导的药物主动外排。MDR 1的表达与缓解率降低和中位总生存期相关。因此，抑制MDR 1介导的外排可能改善治疗结果。Zosuquidar trihydrochloride（LY 335979）是一种特异性和强效的MDR 1介导的外排调节剂。此外，它与柔红霉素（治疗AML的基本药物）的药代动力学相互作用极小。目前的临床试验需要采集和保存血浆样本，用于安慰剂或Zosuquidar存在下柔红霉素和阿糖胞苷的药代动力学分析。要求GCRC提供支持，以处理全血样本。患者将不会接受GCRC的方案治疗。新诊断的AML或晚期MDS患者将入住5 N大学医院的保护环境室。患者将接受常规诱导化疗（每天给予三剂柔红霉素和连续输注阿糖胞苷），此外还将接受安慰剂或佐舒奎达，每天6小时，每次给予柔红霉素。在柔红霉素第三次给药前即刻和接下来的4天（6份样本），采集患者的血液样本用于柔红霉素和阿糖胞苷的药代动力学分析。