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

Evaluation of the Effects of Local GM-CSF-in-Adjuvant Administration on Dendritic Cells in Skin of Melanoma Patients and in Sentinel Lymph Nodes

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.

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.