evaluation of the effects of local granulocyte-macrophage colony-stimulating factor (gm-csf) in adjuvant administration on dendritic cells in skin of melanoma patients and in sentinel lymph nodes: mel38

Conditions: Melanoma

Summary: goal: to characterize the cellular events that occur in vivo after vaccination with an emulsion of gmcsf-in-adjuvant. design: open-label, single dose study in two stages.

regimen: each injection will be administered to patients with clinical stage i or ii melanoma, who have had complete excision of a primary melanoma, but prior to wide excision with or without sentinel node biopsy as definitive surgical therapy. in stage 1: patients will be injected with a 1 ml emulsion containing gm-csf in saline plus montanide isa-51 adjuvant, in skin adjacent to a melanoma biopsy scar. in stage 2: patients will be randomized to receive an injection of one of the following in skin adjacent to the melanoma biopsy scar: 1. 1 ml saline 2. gm-csf in 1 ml saline 3. an emulsion of montanide isa-51 adjuvant and saline 4. an emulsion of gm-csf in saline plus ml montanide isa-51 adjuvant. all vaccines will be administered intradermally. after the injection, each patient will undergo wide excision of the melanoma site, with or without sentinel node biopsy, as clinically indicated.

Eligibility criteria:
inclusion criteria: * patients who have been diagnosed, by histologic and clinical examination, with resected ajcc stage i or ii melanoma. * patients who have any evidence of metastasis will not be eligible. * all patients must have: 1. karnofsky performance of 80% or higher 2. ecog performance status of 0 or 1 3. ability and willingness to give informed consent * laboratory parameters as follows: 1. anc: 90% of lower limit of normal (lln) to 120% of upper limit of normal (uln) 2. platelets: 100-500 x 103/ul 3. hgb: 90% lln to 120% uln 4. hepatic: 1. ast, alt, bilirubin, and alk phos within normal limits, 2. ldh up to 1.2 x uln 5. renal: 1. creatinine up to 1.5 x uln * age 18-85 years at the time of study entry. exclusion criteria: * patients who are currently receiving cytotoxic chemotherapy, interferon, or radiation or who have received this therapy within the preceding 12 weeks. * patients with known or suspected allergies to any component of the vaccine. * patients receiving the following medications at study entry or within the preceding 4 weeks are excluded: * agents with putative immunomodulating activity (with the exception of non-steroidal anti-inflammatory agents), * allergy desensitization injections, * corticosteroids, administered parenterally or orally. topical corticosteroids are acceptable. * any growth factors, interleukin-2 or other interleukins. * pregnancy or the possibility of becoming pregnant during vaccine administration. female patients of child-bearing potential must have a negative pregnancy test (urinary or serum beta-hcg) prior to administration of the injection. * patients in whom there is a medical contraindication or potential problem in complying with the requirements of the protocol, in the opinion of the investigator. * patients classified according to the new york heart association classification as having class iii or iv heart disease. * patients with serious symptomatic active pulmonary disease, with pleural effusions, or with a history of pulmonary edema. * patients who have systemic autoimmune disease with visceral involvement. * patients with clinically apparent skin infection or other clinically evident inflammation involving the skin adjacent to the melanoma biopsy scar.

Keywords: melanoma adjuvant dendritic cells vaccine