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: Phase II trial to study the effectiveness of vaccine therapy, interferon gamma, and interleukin-2 in treating patients who have stage III or stage IV melanoma.

Condition	Treatment or Intervention	Phase
stage III melanoma Stage IV Melanoma Recurrent Melanoma	Drug: CD40-ligand  Drug: Candida albicans skin test reagent  Drug: MART-1 antigen  Drug: autologous dendritic cells  Drug: gp100 antigen  Drug: interferon gamma  Drug: interleukin-2  Drug: interleukin-4  Drug: sargramostim  Drug: tumor infiltrating lymphocytes  Drug: tyrosinase peptide  Procedure: biological response modifier therapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: interferon therapy  Procedure: interleukin therapy  Procedure: leukocyte therapy  Procedure: non-specific immune-modulator therapy  Procedure: non-tumor cell derivative vaccine  Procedure: tumor infiltrating lymphocyte therapy  Procedure: tumor necrosis factor therapy  Procedure: vaccine therapy	Phase II

Further Study Details: 

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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

California
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90089,  United States

Study chairs or principal investigators

Jeffrey S. Weber, MD, PhD,  Study Chair,  University of Southern California   

Study ID Numbers:  CDR0000068125; LAC-USC-10M991; NCI-G00-1837; NCI-T99-0102
Record last reviewed:  October 2003
Last Updated:  October 13, 2004
Record first received:  August 3, 2000
ClinicalTrials.gov Identifier:  NCT00006113
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08