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

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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.