Vaccine Therapy in Treating Patients With Stage IV Melanoma

OBJECTIVES: I. Determine the safety and tolerability of intranodal Synchrotope TA2M plasmid DNA vaccine in patients with stage IV melanoma. II. Determine the immune response of patients treated with this vaccine. III. Determine the clinical response of patients treated with this vaccine.

OUTLINE: This is dose-escalation, multicenter study. Patients receive Synchrotope TA2M plasmid DNA vaccine intranodally continuously over 96 hours beginning on days 0, 14, 28, and 42. Treatment continues for up to 2 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 8 patients receive escalating doses of Synchrotope TA2M plasmid DNA vaccine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 2 of 8 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: Approximately 16-24 patients will be accrued for this study within 12 months.

Inclusion criteria

- Patient must meet the following during the screening and baseline visits:

• The patients or their legally acceptable representative must give signed informed consent for participation in the study before any study procedure is performed.
• Patients must be 18 years of age or older at pre-study
• Patients must be ambulatory, ECOG performance status of 0 or 1 (Appendix II)
• Patients have histologically confirmed diagnosis of Stage IV melanoma according to AJCC/UICC modified system with an expected survival time of more than 3 months
• Patients must be positive for HLA-A2 (Patients tested positive within 5 years of pre-study screening do not need to be tested again for HLA-A2)
• Patients must agree to use an acceptable method of birth control

• intrauterine device
• oral hormonal contraception
• combination of spermicide and barrier method or
• abstinence
• Female patients of childbearing potential must have a confirmed negative urine pregnancy test on Day 0

Exclusion criteria

- Patients meeting any of the following criteria will NOT be eligible for the study:

• Patients who have hematological abnormalities as evidenced by:

• Neutrophils < 1,500/mm3
• Leukocytes < 3,000/mm3
• Platelets < 75,000/mm3
• Hemoglobin < 9.0 g/dL
• Patients who have hepatic disease as evidenced by:

• SGOT/SGPT (AST/ALT) > 2.5 x the upper limit of normal (ULN)
• alkaline phosphatase > 2.5 x ULN
• Bilirubin > 1.5 x ULN\\
• positive for hepatitis B surface antigen
• positive for hepatitis C antibody
• Patients who have known or suspected renal impairment as evidenced by:

• serum creatinine > 1.5 x ULN, and/or
• serum urea > 2.6 x ULN
• Patients with a history of ocular melanoma
• Patients with brain metastases, unless completed resected
• Patients with a positive HIV antibody test
• Patients with medical, sociological, or psychological impediments that may compromise compliance with the protocol
• Patients who are nursing, pregnant or planning to become pregnant within 6 months of treatment completion
• Patients who are receiving chemo-, radio- or immunotherapy concurrently or within the preceding four weeks
• Patients who are taking drugs that affect immune function such as systemic corticosteroids or immunomodulatory drugs concurrently or within the preceding four weeks
• Patients who are receiving any investigational drug concurrently or within the preceding four weeks