Vaccine Therapy Followed by Biological 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 melanoma cells may make the body build an immune response to kill tumor cells. Biological therapies such as interferon gamma and interleukin-2 use different ways to stimulate the immune system and stop cancer cells from growing. Combining vaccine therapy with biological therapy may kill more tumor cells. PURPOSE: This phase II trial is studying giving vaccine therapy together with interferon gamma and interleukin-2 in treating patients with stage III or stage IV melanoma.

Detailed Description
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OBJECTIVES: Determine the clinical response rate and immune response in HLA-A2 positive patients with stage III or IV melanoma after receiving autologous dendritic cells pulsed with melanoma antigen peptides (MART-1:26-35, gp100:209-217, and tyrosinase:368-376) and treated ex vivo with CD40-ligand and interferon gamma, followed by interleukin-2 in vivo. Determine the toxicities of this regimen in these patients. OUTLINE: This is a multicenter study. Patients undergo leukapheresis to harvest autologous dendritic cells (ADCs). Melanoma peptides (MART-1:26-35, gp100:209-217, and tyrosinase:368-376) are pulsed separately onto ADCs, which are also treated ex vivo with CD40-ligand, interferon gamma, interleukin-4, sargramostim (GM-CSF), and Candida albicans skin test reagent. Patients receive each melanoma peptide pulsed ADC vaccine separately via 3 successive 10 minute infusions on day 1. Patients then receive interleukin-2 subcutaneously every 12 hours on days 2-6. Treatment repeats every 2 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients are followed at 4 weeks, then every 3 months for 2 years, then every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 21-41 patients will be accrued for this study within 18-24 months.

Official Title
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A Phase II Trial of a MART-1/gp100/Tyrosinase Peptide-Pulsed Dendritic Cell Vaccine Treated With CD40 Ligand/Gamma Interferon With Subcutaneous IL-2 for Patients With Metastatic Melanoma

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: MART-1 antigen
* Biological: aldesleukin
* Biological: gp100 antigen
* Biological: recombinant CD40-ligand
* Biological: recombinant interferon gamma
* Biological: recombinant interleukin-4
* Biological: sargramostim
* Biological: therapeutic autologous dendritic cells
* Biological: therapeutic tumor infiltrating lymphocytes
* Biological: tyrosinase peptide
* Radiation: Candida albicans skin test reagent


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed metastatic melanoma Measurable disease after attempted curative surgery Unresectable stage III or IV uveal melanoma Metastatic mucosal melanoma HLA-A2.1 positive No disease progression following high dose interleukin-2 (600,000 or 720,000 IU/kg every 8 hours) PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-1 Life expectancy: Not specified Hematopoietic: WBC at least 3,000/mm^3 Platelet count at least 75,000/mm^3 Hemoglobin at least 9.0 g/dL No coagulation disorders Hepatic: Bilirubin no greater than 2.0 mg/dL Renal: Creatinine no greater than 2.0 mg/dL Cardiovascular: No myocardial infarction within the past 6 months Patients with documented or suspected coronary artery disease must undergo stress thallium test No major cardiovascular illness Pulmonary: No major pulmonary illness Immunologic: HIV negative Hepatitis B surface antigen negative Hepatitis C antibody negative No history of uveitis or autoimmune inflammatory eye disease Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No major systemic infection No other malignancy within the past 5 years except curatively treated carcinoma in situ of the cervix or basal cell skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics No prior MART-1:26-35, gp100:209-217, or tyrosinase:368-376 antigens Chemotherapy: At least 1 month since prior chemotherapy for melanoma Endocrine therapy: No concurrent steroid therapy Radiotherapy: At least 1 month since prior radiotherapy for melanoma Surgery: See Disease Characteristics Other: At least 1 month since prior adjuvant therapy for melanoma At least 1 month since other prior therapy for melanoma

Ages Eligible for Study
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Minimum Age: 18 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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: MART-1 antigen|nan|
|Biological: aldesleukin|nan|
|Biological: gp100 antigen|nan|
|Biological: recombinant CD40-ligand|nan|
|Biological: recombinant interferon gamma|nan|
|Biological: recombinant interleukin-4|nan|
|Biological: sargramostim|nan|
|Biological: therapeutic autologous dendritic cells|nan|
|Biological: therapeutic tumor infiltrating lymphocytes|nan|
|Biological: tyrosinase peptide|nan|
|Radiation: Candida albicans skin test reagent|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 III melanoma, stage IV melanoma, recurrent melanoma