RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Combining an immune adjuvant with a vaccine may cause a stronger immune response and kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of immune adjuvant when given together with vaccine therapy and to see how well they work in treating patients with stage IIB, stage IIC, stage III, or stage IV melanoma.

Condition	Treatment or Intervention	Phase
Recurrent Melanoma stage II melanoma stage III melanoma Stage IV Melanoma	Drug: gp100 antigen  Drug: sargramostim plasmid DNA melanoma vaccine  Drug: tyrosinase peptide  Procedure: biological response modifier therapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: gene therapy  Procedure: non-tumor cell derivative vaccine  Procedure: vaccine therapy	Phase I Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the maximum tolerated dose and recommended dose of sargramostim (GM-CSF) plasmid DNA adjuvant with a multi-epitope peptide vaccine comprising tyrosinase peptide and gp100 antigen in patients with stage IIB, IIC, III, or IV melanoma who are HLA-A2-positive.
• Determine the safety of this regimen in these patients.
• Determine the pharmacokinetics of this regimen in these patients.
• Determine the dose-limiting toxic effects of this regimen in these patients.
• Determine the immunogenicity of this regimen in these patients.

Secondary

• Determine any anti-tumor response in patients treated with this regimen.

OUTLINE: This is a phase I, pilot, dose-escalation study of sargramostim (GM-CSF) plasmid DNA adjuvant followed by a phase II, pilot study.

• Patients receive GM-CSF plasmid DNA adjuvant subcutaneously (SC) on day 1 and a vaccine comprising tyrosinase peptide and gp100 antigen SC on day 5. Treatment repeats every 28 days for a total of 3 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of GM-CSF plasmid DNA adjuvant until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
• Phase II: Patients receive vaccination as in phase I at the MTD. Patients are followed at least once annually for at least 15 years.

PROJECTED ACCRUAL: A total of 3-27 patients (3-18 for phase I and 9 for phase II) will be accrued for this study within 2-14 months.

Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant melanoma
• Stage IIB, IIC, III, or IV disease
• Patients with resectable disease must have undergone surgical resection before study entry
• Patients free of disease after surgical resection are eligible up to 6 months after resection
• HLA-A0201 positive
• No detectable brain metastases by brain MRI or CT scan

PATIENT CHARACTERISTICS: Age

• Any age if weight > 25 kg (55 lb)

Performance status

• Karnofsky 80-100%

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 3,000/mm^3
• Platelet count ≥ 100,000/mm^3
• No active bleeding

Hepatic

• Lactic dehydrogenase ≤ 2 times upper limit of normal (ULN)
• Albumin ≥ 3.5 mg/dL
• AST ≤ 2 times ULN

Renal

• Creatinine ≤ 2 mg/dL
• No prior creatinine > 2 mg/dL

Other

• Must weigh ≥ 25 kg
• No medical condition that would preclude study participation (e.g., active autoimmune disease or immunodeficiency)
• No pre-existing retinal or choroidal eye disease
• No inflammation of the eyes
• No serious underlying medical conditions
• No active infection requiring antimicrobial drugs
• Not pregnant or nursing
• At least 3 months post-partum
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for 3 months after study participation

PRIOR CONCURRENT THERAPY: Biologic therapy

• More than 4 weeks since prior immunotherapy
• No prior vaccines containing tyrosinase peptide or gp100 antigen or peptides derived from tyrosinase peptide or gp100 antigen
• No other concurrent immunotherapy

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
• No concurrent chemotherapy

Endocrine therapy

• More than 6 weeks since prior systemic corticosteroids
• Inhaled or nasal steroids allowed

Radiotherapy

• More than 4 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery

• See Disease Characteristics
• Recovered from prior surgery

Other

• Recovered from all prior therapy
• No concurrent medication that would preclude study participation

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting

Study chairs or principal investigators

Miguel-Angel Perales, MD,  Principal Investigator,  Memorial Sloan-Kettering Cancer Center   
Paul B. Chapman, MD,  Principal Investigator,  Memorial Sloan-Kettering Cancer Center   
Alan N. Houghton, MD,  Principal Investigator,  Memorial Sloan-Kettering Cancer Center   
Jedd D. Wolchok, MD,  Principal Investigator,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000367330; MSKCC-00142A; NCI-5906; NCT00085137
Record last reviewed:  August 2004
Last Updated:  March 10, 2005
Record first received:  June 10, 2004
ClinicalTrials.gov Identifier:  NCT00085137
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08