Vaccine Therapy Compared With Interferon Alfa in Treating Patients With Stage III Melanoma

OBJECTIVES: I. Compare the relapse-free and overall survival rates in patients with stage
III melanoma treated with autologous tumor vaccine versus interferon alfa-2b as postsurgical
adjuvant therapy. II. Compare the safety and tolerability of these regimens in this patient
population.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified
according to number of metastatic lymph node sites (1 vs more than 1), number of positive
lymph nodes in a single site (none vs 1 or more), presence of intransit metastases (yes vs
no), and evidence of extranodal extension (yes vs no). Patients are randomized to one of two
treatment arms. Arm I: Patients receive autologous tumor cell vaccine intradermally once a
week for 7 weeks followed by a booster injection at 6 months. BCG is given concurrently with
vaccine as an immune-stimulator for doses 2-8. Patients also receive cyclophosphamide 6 days
after the first vaccine injection. Arm II: Patients receive interferon alfa-2b IV for 5
consecutive days a week for 4 weeks followed by maintenance doses given subcutaneously 3
times a week for 48 weeks. Patients are followed monthly for 1 year, every 2 months for 1
year, every 3 months for 1 year, and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 386-425 patients will be accrued for this study.

DISEASE CHARACTERISTICS: Histologically confirmed melanoma metastatic to regional lymph
nodes with a clinically palpable mass Must have clinical evidence of the following:
Metastases in 1 nodal site All other nodes microscopically negative No intransit
metastases No extranodal extension OR Metastases in more than 1 nodal site More than 1
positive lymph node in a single site Intransit metastases Extranodal extension Must have
undergone complete resection of tumor, measuring at least 2 cm in diameter, within the
past 6 weeks No distant metastases

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 80-100% Life
expectancy: At least 6 months Hematopoietic: Hematocrit at least 30% WBC at least
3,000/mm3 Hepatic: Hepatitis B and C negative Renal: Not specified Other: Not pregnant or
nursing No active serious infection No active autoimmune disease HIV negative No other
malignancy within the last 5 years except squamous cell carcinoma of the skin, carcinoma
in situ of the cervix, superficial bladder carcinoma, early stage prostate cancer, or
noninvasive melanoma No active severe depression or psychiatric disorder with psychotic
symptoms No uncontrolled thyroid abnormalities

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 6 weeks
since prior cytotoxic drugs (except for isolated limb perfusion) Endocrine therapy: No
concurrent systemic corticosteroids Radiotherapy: At least 6 months since prior
radiotherapy Surgery: See Disease Characteristics Other: At least 30 days since prior
investigational drugs