M-Vax + Low Dose Interleukin-2 Versus Placebo Vaccine in Metastatic Melanoma in Patients With Stage IV Melanoma

M-Vax is a therapeutic melanoma vaccine consisting of autologous melanoma cells that have been irradiated and then modified with the hapten, dinitrophenyl (DNP). There is a large amount of published evidence that hapten modification makes visible to the immune system antigens, including tumor antigens, that otherwise do not elicit an immune response. This is a Phase III, randomized, placebo-controlled, double-blind, multi-centered trial of M-Vax in patients with stage IV melanoma with measurable metastases in lung and/or soft tissues. To be eligible for screening, patients will have undergone surgery for therapeutic intervention, which yields an adequate amount of melanoma tumor cells for preparation of vaccines, which pass vaccine release testing. Eligible patients who meet all inclusion/exclusion criteria will be enrolled in the study. Patients will be assigned in a double-blind fashion to M-Vax or Placebo Vaccine at a 2:1 ratio (M-Vax:Placebo Vaccine). The dose of M-Vax will be 4.0-20.0x10(6) DNP-modified autologous melanoma tumor cells. The Placebo Vaccine will consist of diluent only. An initial dose of M Vax or Placebo Vaccine will be administered without BCG followed by low dose cyclophosphamide (300 mg/m2 iv). Then M Vax or Placebo Vaccine mixed with Bacillus of Calmette and Guérin (BCG) will be administered weekly for 6 weeks. Four courses of interleukin-2 (IL2) will be administered to all patients starting about 2 weeks after the last vaccine; each course will consist of 3 million units/m2 subcutaneously daily for 5 days followed by a 16-day rest period. The primary endpoints of the study are: 1)Best overall anti-tumor response, and 2)Survival, measured by % surviving at two years. Patients will be evaluated for anti-tumor response by modified RECIST criteria between weeks 24 and 25 (i.e., 5-6 weeks after completion of IL2). At the 6-month point patients who remain on study will receive an additional single booster dose of M-Vax or Placebo Vaccine mixed with BCG. This will be followed by four more courses of IL2. Two additional evaluations for anti-tumor response will take place at the 38-39 week (month 9) and one-year points. Then patients will be regularly evaluated for tumor status and adverse events until evidence of tumor progression that requires new therapy. Patients who remain on-study will be followed until death but for a maximum of 5 years. The intended sample size is 387, and there will be about 25 sites participating in the United States, Europe, and Israel. An interim analysis will be performed after half the patients have been accrued.