Patient case: 62-year-old female with mucosal melanoma; genetic feature: KIT (L576P), KIT amplification

Clinical trial: Vaccine Therapy Followed by Biological Therapy in Treating Patients With Stage III or Stage IV Melanoma

Summary: 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: 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.

Eligibility: 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

Relevance to patient case: not relevant