Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma

Study Overview
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Brief Summary
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RATIONALE: Vaccines made from a patient's dendritic cells may make the body build an immune response to kill tumor cells. It is not yet known whether combining vaccine therapy with either gp100 antigen or the patient's tumor cells will cause a stronger immune response and kill more tumor cells. PURPOSE: This randomized phase II trial is studying vaccine therapy and gp100 antigen to see how well they work compared to vaccine therapy and patient's tumor cells in treating patients with stage III or stage IV melanoma.

Detailed Description
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OBJECTIVES: Primary Compare the tumor-specific immune response, in terms of the number of gp100-specific cytotoxic T-lymphocytes, T-cell production of interferon gamma, or T-cell proliferation in response to in vitro exposure to gp100 and tumor lysate, in patients with stage III or IV melanoma treated with autologous dendritic cells (DC) pulsed with gp100 antigen vs autologous DC fused with autologous tumor cells. Secondary Compare the safety and toxicity of these regimens in these patients. Compare the therapeutic effect of these regimens in these patients. OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms. All patients undergo leukapheresis. Peripheral blood mononuclear cells are cultured to generate dendritic cells (DC). Arm I: Patients undergo surgical harvesting of tumor cells for subsequent fusion. Patients receive vaccination comprising DC fused with autologous tumor cells subcutaneously on day 1. Treatment repeats every 21 days for 3 courses. Patients who achieve a partial (PR) or complete response (CR) may receive an additional 3 courses. Arm II: Patients receive vaccination comprising DC pulsed with gp100 antigen IV on day 1. Treatment repeats every 21 days for 6 courses. Patients who achieve a PR or CR may receive an additional 6 courses. In both arms, patients are followed monthly for 6 months. PROJECTED ACCRUAL: A total of 40 patients (20 per treatment arm) will be accrued for this study.

Official Title
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A Randomized Phase II Study of Immunization Against Melanoma Comparing Autologous Dendritic Cells Pulsed With gp100 Peptide to Autologous Dendritic Cells Fused With Autologous Tumor Cells

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: autologous dendritic cell-tumor fusion vaccine
* Biological: gp100 antigen
* Biological: therapeutic autologous dendritic cells


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed cutaneous melanoma Stage III or IV disease Recurrent or de novo stage III disease allowed if disease is unresectable and no definitive treatment is available gp100- and HLA-A201-positive Surgically accessible tumor, defined by 1 of the following: Pulmonary lesions approachable by thoracoscopic procedure Skin or superficial soft tissue or lymph node lesions amenable to resection under local anesthesia Malignant ascites or pleural effusion Measurable disease in addition to surgically accessible tumor > 2.0 cm No CNS metastases No mucosal or ocular melanoma PATIENT CHARACTERISTICS: Age Any age Performance status ECOG 0-1 Life expectancy More than 3 months Hematopoietic WBC > 3,000/mm^3 Platelet count > 75,000/mm^3 Hepatic Bilirubin < 2.0 mg/dL Renal Creatinine < 2.0 mg/dL Immunologic No active infection requiring treatment No clinically significant autoimmune disorder No immune deficiency disorder HIV negative Other Antecubital vein accessible for leukapheresis No other malignancy within the past 5 years except nonmelanoma skin cancer or squamous cell carcinoma in situ of the cervix No pre-existing comorbid disease that would preclude study compliance Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception PRIOR CONCURRENT THERAPY: Biologic therapy No prior melanoma vaccine therapy More than 6 weeks since prior immunotherapy Chemotherapy No prior chemotherapy for metastatic melanoma Endocrine therapy No concurrent corticosteroids Radiotherapy More than 6 weeks since prior radiotherapy Surgery Not specified Other No concurrent systemic immunosuppressive therapy
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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients undergo surgical harvesting of tumor cells for subsequent fusion. Patients receive vaccination comprising dendritic cells (DC) fused with autologous tumor cells subcutaneously on day 1. Treatment repeats every 21 days for 3 courses. Patients who achieve a partial (PR) or complete response (CR) may receive an additional 3 courses. | Biological: autologous dendritic cell-tumor fusion vaccine<br>* Given subcutaneously<br>|
| Experimental: Arm II<br>Patients receive vaccination comprising DC pulsed with gp100 antigen IV on day 1. Treatment repeats every 21 days for 6 courses. Patients who achieve a PR or CR may receive an additional 6 courses. | Biological: gp100 antigen<br>* Given IV<br>Biological: therapeutic autologous dendritic cells<br>* Given IV<br>|

What is the study measuring?
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Primary Outcome Measures

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

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