Monoclonal Antibody and Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma That Has Been Removed During Surgery

Study Overview
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Brief Summary
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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.

Detailed Description
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OBJECTIVES: 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.

Official Title
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An Open-label Study Of MDX-CTLA4 In Combination With Tyrosinase/gp100/MART-1 Peptides Emulsified With Montanide ISA 51 In The Treatment Of Patients With Resected Stage III Or Stage IV Melanoma

Conditions
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Intraocular Melanoma, Melanoma (Skin)

Intervention / Treatment
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* Biological: MART-1 antigen
* Biological: gp100 antigen
* Biological: incomplete Freund's adjuvant
* Biological: ipilimumab
* Biological: tyrosinase peptide
* Procedure: adjuvant therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: 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 MART-1 Failed (or ineligible for or refusal of) interferon alfa PATIENT CHARACTERISTICS: Age: Not specified Performance status: Karnofsky 60-100% Life expectancy: At least 12 months Hematopoietic: 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% Hepatic: 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 Renal: Creatinine less than 1.25 times ULN Immunologic: 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 ISA-51 Other: 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 cervix No underlying medical condition that would preclude study Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic 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 Chemotherapy: At least 4 weeks since prior chemotherapy for melanoma Endocrine therapy: At least 4 weeks since prior hormonal therapy for melanoma At least 4 weeks since prior corticosteroids No concurrent systemic or topical corticosteroids Radiotherapy: At least 4 weeks since prior radiotherapy for melanoma Surgery: See Disease Characteristics Other: 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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: MART-1 antigen|nan|
|Biological: gp100 antigen|nan|
|Biological: incomplete Freund's adjuvant|nan|
|Biological: ipilimumab|nan|
|Biological: tyrosinase peptide|nan|
|Procedure: adjuvant therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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iris melanoma, ciliary body and choroid melanoma, small size, ciliary body and choroid melanoma, medium/large size, extraocular extension melanoma, recurrent intraocular melanoma, stage III melanoma, stage IV melanoma, recurrent melanoma