RATIONALE: Vaccines made from peptides may make the body build an immune response to kill
tumor cells. Monoclonal antibodies can locate tumor cells and either kill them or deliver
tumor-killing substances to them without harming normal cells. Combining vaccine therapy
with a monoclonal antibody may cause a stronger immune response and kill more tumor cells.
PURPOSE: Phase II trial to study the effectiveness of combining vaccine therapy with
monoclonal antibody therapy in treating patients who have stage IV melanoma.
- Determine the clinical response in patients with stage IV melanoma when treated with
anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody combined with
gp100:209-217 and gp100:280-288 peptides emulsified in Montanide ISA-51.
- Determine a safety and adverse event profile of this regimen in these patients.
- Determine improved immunologic response in patients treated with this regimen.
OUTLINE: This is an open-label study.
Patients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody IV
over 90 minutes immediately followed by gp100:209-217 and gp100:280-288 peptides emulsified
in Montanide ISA-51 subcutaneously on days 1, 22, 43, and 64. Treatment repeats every 12
weeks in the absence of disease progression or unacceptable toxicity.
Patients are followed at 3 weeks, every 3 months for 1 year, every 6 months for 2 years, and
then annually thereafter.
PROJECTED ACCRUAL: A total of 68 patients will be accrued for this study within 2 years.
- Histologically confirmed stage IV melanoma
- Mucosal or ocular melanoma allowed
- Clinically evaluable disease
- HLA-A*0201 positive
- 16 and over
- Karnofsky 60-100%
- At least 6 months
- WBC at least 2,500/mm^3
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Hemoglobin at least 10 g/dL
- Hematocrit at least 30%
- AST no greater than 3 times upper limit of normal (ULN)
- Bilirubin no greater than ULN (less than 3.0 mg/dL in patients with Gilbert's
- Hepatitis B surface antigen negative
- Hepatitis C antibody nonreactive
- Creatinine less than 2.0 mg/dL
- Antinuclear antibody negative
- Thyroglobulin antibody normal
- Rheumatoid factor normal
- HIV negative
- No prior autoimmune disease (including uveitis and autoimmune inflammatory eye
- No active infection
- No hypersensitivity to Montanide ISA-51
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the
- No other underlying medical condition that would preclude study therapy
PRIOR CONCURRENT THERAPY:
- At least 3 weeks since prior immunotherapy for melanoma and recovered
- No prior gp100 peptides
- No prior anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody
- At least 3 weeks since prior chemotherapy for melanoma and recovered
- No concurrent chemotherapy
- At least 3 weeks since prior hormonal therapy for melanoma and recovered
- At least 4 weeks since prior systemic or topical corticosteroids
- No concurrent topical or systemic corticosteroids
- At least 3 weeks since prior radiotherapy for melanoma and recovered
- Not specified
- No other concurrent immunosuppressive agents (e.g., cyclosporine and its analog)