RATIONALE: Vaccines made by inserting a laboratory-treated gene into a person's white blood cells may make the body build an immune response to kill tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of vaccine therapy in treating patients who have stage IV or recurrent malignant melanoma.

Condition	Treatment or Intervention	Phase
Stage IV Melanoma Recurrent Melanoma	Drug: dendritic cell-MART-1 peptide vaccine  Procedure: biological response modifier therapy  Procedure: gene therapy  Procedure: recombinant viral vaccine  Procedure: vaccine therapy	Phase I Phase II

Further Study Details: 

OBJECTIVES:

• Determine the safety of vaccination with MART-1 adenovirus-transduced dendritic cells in patients with stage IV or recurrent malignant melanoma.
• Determine the immunological and clinical responses of patients receiving this vaccine.

OUTLINE: This is a dose-escalation study.

Patients undergo leukapheresis. Mononuclear cells are isolated and dendritic cells (DC) are generated. DC are incubated with the adenoviral vector containing MART-1. Patients receive MART-1 adenovirus-transduced dendritic cell (AdVMART1/DC) vaccine intradermally on days 0, 14, and 28. Patients with a significant clinical or immunological response are eligible for 6 additional monthly vaccinations.

Cohorts of 3-6 patients receive escalating doses of the AdVMART1/DC vaccine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed on weeks 1, 4, and 12 and then for survival.

PROJECTED ACCRUAL: A total of 6-36 patients will be accrued for this study.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed stage IV or recurrent malignant melanoma
• HLA-A2.1 and/or HLA-DR4 positive and MART-1 expression determined by reverse transcription polymerase chain reaction or immunohistochemistry
• No uncontrolled CNS metastases
• CNS metastases allowed if treated with CNS irradiation to control local tumor growth

PATIENT CHARACTERISTICS: Age:

• Over 18

Performance status:

• Karnofsky 70-100%

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count greater than 1,000/mm^3
• WBC greater than 3,000/mm^3
• Hemoglobin greater than 9.0 g/dL
• Platelet count greater than 100,000/mm^3

Hepatic:

• Not specified

Renal:

• Not specified

Cardiovascular:

• No prior evidence of New York Heart Association class III-IV cardiac insufficiency
• No coronary artery disease
• No acute ischemic heart disease that would preclude anesthesia or surgery

Pulmonary:

• No acute lung disease that would preclude anesthesia or surgery

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Positive skin test to common antigens (e.g., tetanus and/or Candida)
• HIV negative
• No prior evidence of opportunistic infection
• No prior clinical evidence of autoimmune disease
• No other underlying condition that would preclude study participation
• No allergies to study reagents
• No other acute medical problem that would preclude anesthesia or surgery

PRIOR CONCURRENT THERAPY: Biologic therapy:

• At least 30 days since prior immunotherapy for melanoma

Chemotherapy:

• At least 30 days since prior chemotherapy for melanoma
• No concurrent chemotherapy

Endocrine therapy:

• No concurrent corticosteroids

Radiotherapy:

• See Disease Characteristics
• At least 30 days since prior radiotherapy for melanoma

Surgery:

• More than 30 days since prior surgery for melanoma
• No prior organ allograft

Other:

• At least 14 days since prior therapy for any acute viral, bacterial, or fungal infection
• No concurrent specific therapy for any acute viral, bacterial, or fungal infection
• No concurrent cyclosporine

California
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States; Recruiting

Study chairs or principal investigators

James S. Economou, MD,  Study Chair,  Jonsson Comprehensive Cancer Center   

Study ID Numbers:  CDR0000069373; UCLA-9707074; NCI-G02-2077; NCT00039325
Record last reviewed:  June 2003
Last Updated:  December 3, 2004
Record first received:  June 6, 2002
ClinicalTrials.gov Identifier:  NCT00039325
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08