A PHASE IB TRIAL OF LEVAMISOLE ALONE AND IN COMBINATION WITH RIFN-GAMMA

左旋咪唑单独使用以及与 RIFN-γ 联合使用的 IB 期试验

• 批准号: 3874552
• 负责人: J W SMITH
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3874552
• 关键词: biological response modifiers; clinical trials; combination cancer therapy; cytokine receptors; dosage; drug administration rate /duration; drug adverse effect; human subject; human therapy evaluation; immunomodulators; interferons; interleukin 2; levamisole; natural killer cells; neoplasm /cancer chemotherapy; neoplasm /cancer immunotherapy

The purpose of this protocol was to take a second look at Levamisole using modern immunological assays in order to determine if there would be a dose of Levamisole or a schedule of Levamisole administration that would produce maximal immunomodulation. This trial was also designed to combine Levamisole with interferon gamma, a cytokine whose immunostimulating properties has been well defined in two previous trials conducted at the Biological Response Modifiers Program. This trial investigated four different doses of Levamisole administered once a day every other day. Two groups of patients were treated, one with small tumor burdens in the adjuvant setting and another group with large tumor burdens in the advanced disease setting. After two weeks of treatment with Levamisole alone, all patients then were treated with the same dose of Levamisole plus interferon gamma 0.1 mg/m subcutaneously every other day. This study determined that Levamisole was toxic at the 10 mg/kg dose level in both groups of patients. A maximum tolerated dose therefore was defined to be 5 mg/kg every other day. At this dose level, treatment was well tolerated with Levamisole alone and with Levamisole plus interferon gamma. Analysis of the immunological assays that have been performed to date indicate the Levamisole enhances natural killer cell activity in a dose- dependent manner. There was a suggestion that the activity was better in the adjuvant setting. Soluble interleukin-2 receptor levels were increased during the combined therapy.

该方案的目的是对左旋咪唑进行二次检查，使用 现代免疫学化验，以确定是否会有剂量 左旋咪唑或左旋咪唑给药时间表 最大限度的免疫调节。这项试验还被设计成将 左旋咪唑联合干扰素γ，一种细胞因子，其免疫刺激作用 属性在之前的两次试验中得到了很好的定义 生物反应调节剂计划。 这项试验研究了四种不同剂量的左旋咪唑 一天一次，隔天一次。两组患者接受了治疗，一组患者接受了 辅助环境中的小肿瘤负荷和另一组大的 晚期疾病背景下的肿瘤负担。在两周的时间里 单独使用左旋咪唑治疗，所有患者随后均接受 相同剂量的左旋咪唑加干扰素伽马0.1 mg/m皮下注射 另一天。 这项研究确定左旋咪唑在10毫克/公斤剂量水平下是毒性的 在两组患者中。因此，定义了最大耐受剂量 每隔一天服用5毫克/公斤。在这个剂量水平上，治疗效果很好。 仅与左旋咪唑耐受，与左旋咪唑加干扰素伽马耐受。 迄今已进行的免疫学检测的分析 表明左旋咪唑在一定剂量内增强了自然杀伤细胞的活性- 依赖的态度。有一种说法是，这项活动在 佐剂设置。可溶性白介素2受体水平升高 在综合治疗期间。