COMBINED HHT AND CYTARABINE AS THERAPY FOR CML

HHT 和阿糖胞苷联合治疗 CML

• 批准号: 2458218
• 负责人: TIMOTHY J ERNST
• 金额: $ 2.15万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 1997-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2458218
• 关键词: blood chemistry; chronic myelogenous leukemia; clinical research; combination cancer therapy; cytosine arabinoside; cytotoxicity; drug hypersensitivity; drug screening /evaluation; harringtonines; hematopoietic stem cells; high performance liquid chromatography; human subject; human therapy evaluation; injection /infusion; neoplasm /cancer pharmacology; statistics /biometry

DESCRIPTION: (Applicant's Abstract) Chronic myelogenous leukemia (CML) is a fatal neoplastic disease of the blood. Current therapy affords cures only to the small minority of patients who receive an allogeneic bone marrow transplant. The applicant and others showed that the alkaloid drug derived from the Pacific Yew tree in the Fujian province of China, Homoharringtonine (HHT), is effective in both the in vitro and in vivo suppression of the growth of CML cells. Furthermore, the applicant showed that HHT is synergistic with the nucleoside analogue, cytosine arabinoside (cytarabine) in suppressing the CML CFU-GM growth in vitro. A clinical protocol has been approved by the NIH, CTEP/NCI and Institutional Review Boards at the Dana-Farber Cancer Institute, Massachusetts General Hospital and the Brigham and Womens Hospitals in Boston to treat patients with CML with HHT and cytarabine. This application is to provide funds to do the clinical research, gather and analyze the clinical data and to do in vitro correlative studies. These studies include pharmacologic measurement of HTT and cytarabine serum levels during the drug infusions. Additionally, in vitro studies of the pluripotent hematologic stem cell in CML are proposed. This includes identification of the stem cell based on a newly described method of isolation. Preliminary studies are proposed to examine the feasibility of using this method to isolate normal stem cells for use in subsequent clinical protocols.

描述：（申请人的摘要）慢性骨髓性白血病（CML） 是血液的致命肿瘤疾病。 当前的疗法提供 仅治愈少数接受同种异体的患者 骨髓移植。 申请人和其他人表明 源自富士省太平洋紫杉的生物碱药物 在中国，同伴（HHT），在体外和 体内抑制CML细胞的生长。 此外， 申请人表明，HHT与核苷类似物是协同作用的 抑制CML CFU-GM生长以抑制CML CFU-GM生长 体外。 NIH批准了临床方案 以及达纳 - 法伯癌症研究所的机构审查委员会 马萨诸塞州综合医院以及杨百翰和妇女医院 波士顿用HHT和Cytarabine治疗CML患者。 这 申请是为进行临床研究，收集和 分析临床数据并进行体外相关研究。 这些 研究包括HTT和细胞丁滨血清的药理测量 药物输注期间的水平。 另外，在体外研究 提出了CML中的多能血液学干细胞。 这包括 基于新描述的方法的干细胞识别 隔离。 提出了初步研究以检查可行性 使用这种方法将正常干细胞隔离以在后续 临床方案。