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.

该方案的目的是使用左旋咪唑再次观察 现代免疫学测定以确定是否存在剂量 左旋咪唑或左旋咪唑给药时间表会产生 最大程度的免疫调节。 该试验还旨在结合 左旋咪唑与干扰素γ，一种细胞因子，其免疫刺激作用 在之前进行的两次试验中已经明确定义了属性 生物反应调节剂计划。 该试验研究了四种不同剂量的左旋咪唑 每天一次，每隔一天一次。 两组患者接受治疗，一组接受 辅助治疗组中肿瘤负荷较小，而另一组肿瘤负荷较大 晚期疾病环境中的肿瘤负担。 两周后 单独使用左旋咪唑治疗，然后所有患者均接受 相同剂量的左旋咪唑加干扰素 γ 0.1 mg/m2 皮下注射，每次 改天。 该研究确定左旋咪唑在 10 mg/kg 剂量水平下具有毒性 在两组患者中。 因此定义了最大耐受剂量 每隔一天5毫克/公斤。 在此剂量水平下，治疗效果良好 单独使用左旋咪唑以及左旋咪唑加干扰素 γ 均可耐受。 迄今为止已进行的免疫学测定分析 表明左旋咪唑可在一定剂量下增强自然杀伤细胞活性 依赖方式。 有人建议该活动在 辅助设置。 可溶性白细胞介素 2 受体水平增加 联合治疗期间。