Monoclonal Antibody With or Without gp100 Peptides Plus Montanide ISA-51 in Treating Patients With Stage IV Melanoma

Study Overview
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Brief Summary
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RATIONALE: Biological therapies, such as MDX-010, work in different ways to stimulate the immune system and stop tumor cells from growing. Vaccines made from gp100 peptides may make the body build an immune response to kill tumor cells. Combining the vaccines with Montanide ISA-51 may cause a stronger immune response and kill more tumor cells. It is not yet known whether monoclonal antibody therapy is more effective with or without vaccine therapy in treating advanced melanoma. PURPOSE: This randomized phase II trial is studying monoclonal antibody therapy alone to see how well it works compared to monoclonal antibody therapy, gp100 peptides, and Montanide ISA-51 in treating patients with stage IV melanoma.

Detailed Description
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OBJECTIVES: Primary Determine the clinical response in patients with stage IV melanoma treated with escalating doses of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) with or without gp100 peptides emulsified in Montanide ISA-51. Secondary Determine the safety and toxicity profile of these regimens in these patients. Determine the immunologic response in patients treated with these regimens. Determine the pharmacokinetics of these regimens in these patients. Determine, in HLA-A*0201-positive patients, the differences in responses between patients previously vaccinated with gp100 peptides and patients not previously vaccinated. OUTLINE: This is a 2-part, partially randomized study. Part I (closed as of 3/7/2005): HLA-A*0201-negative patients: Patients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) IV over 90 minutes on day 1. Treatment repeats every 3 weeks for up to 6 doses (3 courses of 3 escalating doses) in the absence of disease progression or unacceptable toxicity. HLA-A*0201-positive patients: Patients are stratified according to prior exogenous gp100 peptide immunization (yes vs no). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive MDX-010 in the same manner as the HLA-A*0201-negative patients. Arm II: Patients receive MDX-010 as in arm I. Patients also receive gp100:209-217 and gp100:280-288 peptides emulsified in Montanide ISA-51 subcutaneously immediately after each MDX-010 infusion. Part II: HLA-A*0201-negative patients (closed as of 3/7/2005): Patients receive MDX-010 as in part I. Treatment repeats every 3 weeks for up to 4 doses (2 courses of 2 escalating doses, beginning with a higher dose level than in part I) in the absence of disease progression or unacceptable toxicity. HLA-A*0201-positive patients: Patients are stratified and randomized as in part I. Arm I: Patients receive MDX-010 in the same manner as the HLA-A*0201-negative patients. Arm II: Patients receive MDX-010 as in arm I. Patients also receive gp100:209-217 and gp100:280-288 peptides emulsified in Montanide ISA-51 subcutaneously immediately after each MDX-010 infusion. In both parts, patients with stable disease or a complete response (CR) after completing all courses of MDX-010 may receive 1 additional course of therapy in the absence of unacceptable toxicity. Patients achieving a partial response may continue to recieve treatment with MDX-010 at the same dose, in the absence of unacceptable toxicity, until CR or until tumor is no longer shrinking. 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 35-179 patients (up to 35 for part I [closed as of 3/7/05] and 69-141 [23-47 per arm (arm I closed as of 3/7/05)] for part II) will be accrued for this study within 3-4 years.

Official Title
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A Study of Intra-Patient Escalating Doses of MDX-010 Given Alone or in Combination With Two gp100 Peptides Emulsified With Montanide ISA-51 in the Treatment of Patients With Stage IV Melanoma

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: gp100 antigen
* Biological: incomplete Freund's adjuvant
* Biological: ipilimumab


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed stage IV melanoma Clinically evaluable or measurable disease No mucosal or ocular melanoma PATIENT CHARACTERISTICS: Age 16 and over Performance status ECOG 0-2 Life expectancy At least 6 months Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 9 g/dL Hematocrit ≥ 28% WBC ≥ 2,500/mm^3 Hepatic AST ≤ 3 times upper limit of normal (ULN) Bilirubin ≤ ULN (< 3 mg/dL for patients with Gilbert's syndrome) Hepatitis B surface antigen negative Hepatitis C virus antibody negative Renal Creatinine < 2 mg/dL Immunologic HIV negative No history of any of the following: Inflammatory bowel disease Regional enteritis Connective tissue disorders (e.g., systemic lupus erythematosus) Rheumatoid arthritis Autoimmune inflammatory eye disease Sjögren's syndrome Inflammatory neurologic disorder (e.g., multiple sclerosis) No active infection No active autoimmune disease that may cause life-threatening symptoms or severe organ/tissue damage Vitiligo, autoimmune thyroiditis, or skin rashes associated with prior therapy are allowed if patient has recovered to grade 1 or less toxicity No systemic hypersensitivity to study agents Prior local reaction (e.g., delayed hypersensitivity or glaucomatous reactions) to Montanide ISA-51 or gp100 injections allowed No autoimmune disease requiring active therapy with any form of steroid or immunosuppressant Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No concurrent underlying medical condition that would preclude study participation 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 PRIOR CONCURRENT THERAPY: Biologic therapy No prior anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody Prior therapy with gp100 peptides or any other immunotherapy allowed Chemotherapy At least 6 weeks since prior nitrosoureas and recovered (toxicity no greater than grade 1) No concurrent chemotherapy Endocrine therapy At least 4 weeks since prior steroids No concurrent systemic, inhaled, optical, or topical corticosteroids Radiotherapy Not specified Surgery Not specified Other At least 3 weeks since prior systemic therapy for melanoma and recovered (toxicity no greater than grade 1) No concurrent immunosuppressive agents (e.g., cyclosporine)

Ages Eligible for Study
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Minimum Age: 16 Years

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
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: gp100 antigen|nan|
|Biological: incomplete Freund's adjuvant|nan|
|Biological: ipilimumab|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response (partial and complete) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety |  |  | 
| Immune response activity |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV melanoma, recurrent melanoma