RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver
tumor-killing substances to them without harming normal cells. Vaccines made from a person's
cancer cells may make the body build an immune response to kill tumor cells.
PURPOSE: Phase I trial to study the effectiveness of combining monoclonal antibody therapy
and vaccine therapy in treating patients who have stage III or stage IV melanoma that has
been removed during surgery.
- Determine the safety and adverse event profile of anti-cytotoxic
T-lymphocyte-associated antigen-4 monoclonal antibody combined with tyrosinase:368-376,
gp100:209-217, and MART-1:26-35 peptides emulsified in Montanide ISA-51 in patients
with resected stage III or IV melanoma.
- Determine if this regimen causes antigen-specific T-cell activation in these patients.
- Determine the clearance profile of this regimen in these patients.
- Assess the development of host immune response in patients treated with this regimen.
OUTLINE: This is a dose-escalation study of anti-cytotoxic T-lymphocyte-associated antigen-4
monoclonal antibody (MDX-CTLA4).
Patients receive tyrosinase:368-376, gp100:209-217, and MART-1:26-35 peptides emulsified in
Montanide ISA-51 subcutaneously followed by MDX-CTLA4 IV over 90 minutes at 0, 1, 2, 3, 4,
5, 8, and 11 months in the absence of disease progression or unacceptable toxicity.
Cohorts of at least 6 patients receive escalating doses of MDX-CTLA4 until the maximum
tolerated dose is determined.
Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then
annually thereafter until disease progression.
PROJECTED ACCRUAL: A total of 18 patients will be accrued for this study.
- Histologically confirmed completely resected stage III or IV melanoma
- Mucosal or ocular subtypes allowed
- HLA-A2 positive
- Positive staining of tumor tissue with antibody HMB-45 for gp100, tyrosinase, and/or
- Failed (or ineligible for or refusal of) interferon alfa
- Not specified
- Karnofsky 60-100%
- At least 12 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%
- Bilirubin no greater than upper limit of normal (ULN)
- AST no greater than 1.25 times ULN
- Hepatitis B surface antigen negative
- Hepatitis C antibody nonreactive
- Creatinine less than 1.25 times ULN
- Antinuclear antibody (ANA) negative OR
- If ANA positive, must be:
- Antithyroglobulin antibody negative
- Rheumatoid factor negative
- Anti-LKM antibody negative
- Anti-phospholipid antibody negative
- Anti-islet cell antibody negative
- Anti-neutrophil cytoplasmic antibody negative
- HIV negative
- No autoimmune disease (e.g., uveitis or autoimmune inflammatory eye disease)
- No active infection
- No hypersensitivity to tyrosinase:368-376, gp100:209-217, MART-1:26-35, or Montanide
- 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 underlying medical condition that would preclude study
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody
- No prior tyrosinase, gp100, or MART-1 peptide
- No prior antitumor vaccination
- No prior interleukin-2
- At least 4 weeks since prior immunotherapy for melanoma
- At least 4 weeks since prior chemotherapy for melanoma
- At least 4 weeks since prior hormonal therapy for melanoma
- At least 4 weeks since prior corticosteroids
- No concurrent systemic or topical corticosteroids
- At least 4 weeks since prior radiotherapy for melanoma
- See Disease Characteristics
- No prior cytotoxic therapy
- At least 4 weeks since any other prior therapy for melanoma
- Concurrent analgesics allowed if on stable dose for at least 2 weeks before study