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

University of Southern California

Status and phase: Terminated; Phase 2

Conditions: Melanoma (Skin)

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

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00006113

CDR0000068125 (10M-99-1)

LAC-USC-10M991

NCI-G00-1837

NCI-T99-0102

Details and patient eligibility

About

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.

Full 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.

Enrollment: 25 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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