vaccine therapy in treating patients with stage iii or stage iv melanoma

Conditions: Intraocular Melanoma; Melanoma (Skin)

Summary: rationale: vaccines made from melanoma cells may make the body build an immune response to kill tumor cells. vaccine therapy plus filgrastim combined with a specific protein may be a more effective treatment for melanoma. purpose: this phase i trial is studying the side effects and best dose of vaccine therapy in treating patients with stage iii or stage iv melanoma that has been completely removed during surgery.

objectives: i. determine the maximum tolerated dose of filgrastim (g-csf)-fetal liver tyrosine kinase-3 (flt3k) fusion protein when combined with melanoma peptide vaccine comprising tyrosinase:368-376 peptide, gp100:209-217 antigen, and mart-1:26-35 antigen emulsified in montanide isa-51 in patients with completely resected stage iii or iv melanoma. ii. determine the toxicity and safety of this regimen in these patients. iii. determine the immune responses to tyrosinase, mart-1, and gp100 antigens in patients before, during, and after receiving these vaccinations. outline: this is a dose escalation, multicenter study of filgrastim (g-csf)-fetal liver tyrosine kinase-3 (flt3k) (g-csf-flt3k) fusion protein. patients receive melanoma peptide vaccine comprising tyrosinase:368-376 peptide, gp100:209-217 antigen, and mart-1:26-35 antigen emulsified in montanide isa-51 subcutaneously (sq) monthly for 6 months, and then at 9 and 12 months for a total of 8 vaccinations. patients receive g-csf-flt3k fusion protein sq daily for 3 days before, immediately after, and then daily for 6 days after each vaccination. cohorts of 6-10 patients receive escalating doses of g-csf-flt3k fusion protein until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 6-10 patients experience dose limiting toxicity. patients are followed every 3 months through year 2 after resection, every 6 months for 3 years, and then annually thereafter until disease progression. projected accrual: a total of 30-50 patients will be accrued for this study within 12-18 months.

Eligibility criteria:
disease characteristics: histologically proven completely resected stage iii or iv cutaneous, mucosal, or ocular melanoma disease free, but at high risk of relapse must meet 1 of the following criteria: failed interferon alfa (ifn-a) therapy ineligible for ifn-a therapy refused ifn-a therapy hla-a2.1 positive availability of tumor tissue for analysis of gp100 antigen staining with antibody hmb-45, and for expression of tyrosinase and mart-1 antigens by immunohistochemistry tumor cells must be positive for at least 1 antigen patient characteristics: age: 18 and over performance status: ecog 0 or 1 life expectancy: not specified hematopoietic: wbc at least 3,000/mm3 granulocyte count at least 1,500/mm3 hemoglobin at least 9.0 g/dl platelet count at least 100,000/mm3 no coagulation or bleeding disorders hepatic: bilirubin no greater than 2.0 mg/dl sgot and sgpt no greater than 2.5 times upper limit of normal renal: creatinine no greater than 2.0 mg/dl cardiovascular: no concurrent major medical illness of the cardiovascular system pulmonary: no concurrent major medical illness of the respiratory system immunologic: hepatitis b surface antigen negative and hepatitis c antibody negative hiv negative no history of uveitis or other autoimmune inflammatory eye disease no other active autoimmune disease no known allergic reaction to montanide isa-51 other: no concurrent major systemic infection including pneumonia or sepsis no concurrent major medical illness of the gastrointestinal system not pregnant or nursing negative pregnancy test no other malignancy within the past 5 years except curatively treated squamous cell skin cancer or carcinoma in situ of the cervix allowed 30 days after treatment prior concurrent therapy: biologic therapy: see disease characteristics no prior tyrosinase:368-376 peptide, gp100:209-217 antigen, or mart-1:26-35 antigen chemotherapy: not specified endocrine therapy: no concurrent steroids radiotherapy: at least 1 month since prior radiotherapy no concurrent radiotherapy surgery: see disease characteristics other: at least 1 month since other prior therapy, including adjuvant therapy, for melanoma no other concurrent anticancer therapy

Keywords: iris melanoma ciliary body and choroid melanoma, small size ciliary body and choroid melanoma, medium/large size extraocular extension melanoma recurrent intraocular melanoma stage iii melanoma stage iv melanoma recurrent melanoma