Vaccine Therapy in Treating Patients With Melanoma

Study Overview
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Brief Summary
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RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Vaccine therapy may be an effective treatment for melanoma. PURPOSE: Randomized phase II trial to study the effectiveness of three vaccine therapy regimens in treating patients who have melanoma.

Detailed Description
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OBJECTIVES: Compare the immunologic activity of three different schedules of peptide immunization with gp100:209-217 (210M) or gp100:17-25 antigen and tyrosinase:368-376 (370D), tyrosinase:240-251 (244S), tyrosinase:206-214 (closed to accrual 11/05/01), or tyrosinase-related protein-1 (ORF3):1-9 peptide (closed to accrual 11/05/01) emulsified in Montanide ISA-51 in patients with melanoma at high risk for recurrence. Compare the response rate to treatment with interleukin-2 (IL-2) after being immunized with this regimen with the usual response rate to IL-2 in this patient population. Determine whether an exploratory cohort of HLA-A2-positive patients demonstrate immunologic activity to immunization with 2 peptides emulsified together. OUTLINE: This is a randomized study. Patients are stratified according to HLA type (A0201 vs A1 vs A3 vs A24 vs A31). (HLA-A24 and HLA-A31 closed to accrual 11/05/01). Patients are randomized to 1 of 3 treatment arms and are given an assigned vaccine, which is emulsified in Montanide ISA-51. HLA typing: HLA-A2: gp100:209-217 (210M) and tyrosinase:368-376 (370D) HLA-A1: tyrosinase:240-251 (244S) HLA-A3: gp100:17-25 HLA-A24: tyrosinase:206-214 (closed to accrual 11/05/01) HLA-A31: tyrosinase-related protein-1 (ORF3):1-9 (closed to accrual 11/05/01) Arm I: Patients receive assigned vaccine subcutaneously (SC) weekly for 10 weeks followed by 3 weeks of no treatment. Arm II: Patients receive assigned vaccine SC on days 1, 22, 43, and 64. Arm III: Patients receive assigned vaccine SC on days 1-4, 22-25, 43-46, and 64-67. Treatment in all arms repeats every 13 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. After the completion of the randomized arms of HLA-A2 patients, additional HLA-A2 patients receive immunization with gp100:209-217 (210M) and tyrosinase:368-376 (370D) emulsified in Montanide ISA-51 SC once every 3 weeks for 4 courses. Patients with progressive disease may receive interleukin-2 IV over 15 minutes every 8 hours for up to 4 days. Treatment repeats every 10-14 days for at least 4 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease or mixed or partial response to treatment may receive additional courses every 2 months. Patients are followed at 6 months. PROJECTED ACCRUAL: A total of 324 patients (19-33 per arm for the HLA-A0201 stratum, 13-16 per arm for the other 4 strata, and 33 per the additional HLA-A2 cohort) will be accrued for this study within 2 years. (HLA-A24 and HLA-A31 closed to accrual 11/05/01).

Official Title
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Randomized Comparison of Three Schedules of Peptide Immunization in Patients With Stage II or III, or Completely Resected Metastatic Melanoma

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: aldesleukin
* Biological: gp100 antigen
* Biological: incomplete Freund's adjuvant
* Biological: tyrosinase peptide


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of melanoma, including one of the following characteristics: Lesions at least 1.5 mm in thickness At least 1 positive lymph node Ulcerated lesion Local recurrence Metastatic lesions completely resected within the past 6 months Clinically disease free within the past 6 weeks HLA-A1, A3, A24, A31, or 0201 positive (HLA-A24 and HLA-A31 closed to accrual 11/05/01) No ocular or mucosal melanoma PATIENT CHARACTERISTICS: Age: 16 and over Performance status: ECOG 0-1 Life expectancy: Not specified Hematopoietic: WBC at least 3,000/mm^3 Platelet count at least 90,000/mm^3 Hepatic: Bilirubin no greater than 1.6 mg/dL (3.0 mg/dL in Gilbert's syndrome) AST and ALT less than 3 times normal Hepatitis B surface antigen negative Renal: Creatinine no greater than 2.0 mg/dL Cardiovascular: For interleukin-2 (IL-2) therapy: No cardiac ischemia, myocardial infarction, or cardiac arrhythmias Stress cardiac test required if abnormal EKG, symptoms of cardiac ischemia or arrhythmia, or older than 50 years Pulmonary: For IL-2 therapy: No obstructive or restrictive pulmonary disease FEV_1 greater than 60% predicted if prolonged history of cigarette smoking or symptoms of respiratory dysfunction Other: Not pregnant Negative pregnancy test Fertile patients must use effective contraception HIV negative No active systemic infections, autoimmune disease, or active primary or secondary immunodeficiency PRIOR CONCURRENT THERAPY: Biologic therapy: At least 3 weeks since prior systemic biologic therapy for melanoma No prior gp100 antigen or tyrosinase or TRP-1 peptide No other concurrent systemic biologic therapy for melanoma Chemotherapy: At least 3 weeks since prior systemic chemotherapy and recovered No concurrent systemic chemotherapy for melanoma Endocrine therapy: At least 3 weeks since prior systemic endocrine therapy for melanoma No concurrent systemic steroid therapy Radiotherapy: At least 3 weeks since prior systemic radiotherapy and recovered No concurrent systemic radiotherapy for melanoma Surgery: See Disease Characteristics

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: aldesleukin|nan|
|Biological: gp100 antigen|nan|
|Biological: incomplete Freund's adjuvant|nan|
|Biological: tyrosinase peptide|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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stage I melanoma, stage II melanoma, stage III melanoma, stage IV melanoma, recurrent melanoma