Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma

DISEASE CHARACTERISTICS:

• Histologically confirmed locoregional or metastatic cutaneous malignant melanoma

  • Stage III or IV disease

    • Stage III: pT4b, N0, M0 (satellite metastases) or any pT, N1 or pT, N1 or N2a-c, M0 (lymph node metastases or in transit intralymphatic metastases)
    • Stage IV: any pT, N1-2, M1a-b
    • Surgically incurable
    • Incurable with standard treatment (i.e., localized chemotherapy/limb perfusion for stage III, systemic chemotherapy for stage IV)
• Unidimensionally or bidimensionally measurable disease by physical examination (e.g., cutaneous metastases) and/or non-invasive radiologic procedures NOTE: Stage III lesions may be measurable lymph nodes after incomplete resection and/or inoperable in transit metastases

• HLA-A1 and/or HLA-A2 expression by serologic HLA typing

  • HLA-A2.01 subtype must be confirmed by polymerase chain reaction on genomic DNA obtained from peripheral blood mononuclear cells

• No active CNS metastases

  • Previously treated CNS metastases (e.g., excision of a single metastasis) allowed if no active disease present by CT scan or MRI

PATIENT CHARACTERISTICS:

Age

• Over 18

Performance status

• Karnofsky 60-100%

Life expectancy

• At least 6 months

Hematopoietic

• WBC greater than 2,500/mm^3
• Neutrophil count greater than 1,000/mm^3
• Lymphocyte count greater than 700/mm^3
• Platelet count greater than 75,000/mm^3
• Hemoglobin greater than 9 g/dL
• No bleeding disorders

Hepatic

• Bilirubin less than 2.0 mg/dL
• No hepatitis B or C

Renal

• Creatinine less than 2.5 mg/dL

Cardiovascular

• No clinically significant heart disease

Pulmonary

• No clinically significant respiratory disease

Immunologic

• No active systemic infection

• No immunodeficiency disease

  • No evidence of HIV-1, HIV-2, or human T-cell lymphocytic virus-1

• No active autoimmune disease including, but not limited to:

  • Lupus erythematosus
  • Autoimmune thyroiditis or uveitis
  • Multiple sclerosis
  • Inflammatory bowel disease NOTE: Vitiligo allowed

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 4 weeks after study participation
• No organic brain syndrome or significant psychiatric abnormality that would preclude study participation and follow-up
• No contraindication to leukapheresis
• No other active malignant neoplasms

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 4 weeks since prior systemic immunotherapy
• No concurrent immunotherapy during and for 2 weeks after last vaccination

Chemotherapy

• See Disease Characteristics
• More than 4 weeks since prior systemic chemotherapy (6 weeks for nitrosoureas [e.g., fotemustine])
• No concurrent chemotherapy during and for 2 weeks after last vaccination

Endocrine therapy

• No concurrent corticosteroids during and for 2 weeks after last vaccination

Radiotherapy

• No prior radiotherapy to the spleen
• Concurrent palliative radiotherapy allowed for selected metastases (e.g., pain or local complications such as compression)

Surgery

• See Disease Characteristics
• Recovered from prior surgery
• No prior splenectomy
• No prior organ allografts
• Concurrent surgery of selected metastases (e.g., pain or local complications such as compression) allowed

Other

• No other concurrent investigational drugs during and for 2 weeks after last vaccination
• No concurrent paramedical substance during and for 2 weeks after last vaccination
• No concurrent participation or intent to participate in another clinical trial

Denileukin diftitox (ONTAK) induces a tolerogenic phenotype in dendritic cells and stimulates survival of resting Treg.

Baur AS1, Lutz MB, Schierer S, Beltrame L, Theiner G, Zinser E, Ostalecki C, Heidkamp G, Haendle I, Erdmann M, Wiesinger M, Leisgang W, Gross S, Pommer AJ, Kämpgen E, Dudziak D, Steinkasserer A, Cavalieri D, Schuler-Thurner B, Schuler G.