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

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The purpose of this protocol was to examine the immunologic effects of levamisole using modern assay techniques in order to determine if an alternate dose and schedule of levamisole administration would produce maximal immunomodulation. Levamisole was also administered in combination with interferon-gamma, a cytokine whose immunomodulatory properties have been well defined in two previous trials conducted at the Biological Response Modifiers Program. Levamisole was administered orally every other day at one of four different dose levels. Two groups of patients were eligible for entry on this trial. One group had advanced metastatic disease and the second group (adjuvant group) was treated after surgical therapy to render the patient disease free. Levamisole alone was administered every other day for a total of six doses. After ten-day rest, the same dose of levamisole was given in combination with interferon-gamma at a dose of 0.1 mg/m sq subcutaneously every other day on the same days as the levamisole. Dose-limiting toxicity was observed at the 10 mg/kg dose of levamisole in both groups of patients. The maximum-tolerated dose was defined as 5 mg/kg every other day. At this dose level, treatment was well tolerated with levamisole alone and with levamisole plus interferon gamma. Levamisole alone produced dose-dependent increases in serum neopterin and soluble interleukin-2 receptor levels. Activation of monocytes was evidenced by increased expression of CD64, the high affinity Fc receptor, and by an increase in the expression of HLA-ABC and HLA-DR antigens.