Randomized trial to determine if neo-adjuvant subcutaneous GM-CSF restores the host regional lymph node immunity

The sentinel lymph nodes in patients with melanoma are immunosuppressed and the investigators have shown this occurs early in the disease process. This regional nodal immunosuppression precedes nodal metastasis and may be required for nodal spread. Administration of GM-CSF has been used to alter the immune response to metastatic melanoma. The investigators propose to assess whether administration of a short course of GM-CSF preoperatively to patients about to undergo wide local excisions and sentinel lymph node dissection can alter the immune environment of the sentinel lymph node and restore an immune surveillance profile in the sentinel lymph node.

Inclusion Criteria

To be eligible for the study, patients must satisfy the following criteria:

• Histologically confirmed primary cutaneous malignant melanoma
• 1-4mm Breslow depth
• Scheduled for sentinel lymph node biopsy as part of their standard surgical management
• Man or woman, age >/= 18 years
• Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 2 weeks after the study in such a manner that the risk of pregnancy is minimized. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy or bilateral oophorectomy) or is not postmenopausal. Sexually active WOCBP must use an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized. All WOCBP must have a negative pregnancy test prior to first receiving GM-CSF.
• Men must agree to use and utilize an adequate method of contraception throughout treatment and for at least 2 weeks after study drug is stopped
• All patients must be willing and able to give written informed consent.

Exclusion Criteria Subjects meeting any of the following criteria are ineligible for study entry

• Clinical stage III or IV disease
• Autoimmune disease: Patients with a history of inflammatory bowel disease are excluded from this study as are patients with a history of immunologic disease (e.g. rheumatoid arthritis, scleroderma, systemic lupus erythematosus, autoimmune vasculitis, motor neuropathy considered of autoimmune origin)
• Any underlying medical conditions which, in the opinion of the investigator, will make the administration of GM-CSF hazardous or obscure the interpretation of adverse events; such as, psychological, familial, sociological or geographical conditions potentially hampering compliance with the study protocol and followup schedule
• Any vaccination therapy within 4 weeks prior to GM-CSF administration
• Concomitant therapy with any of the following within the past 3 months: GM-CSF, interferon, other non-study immunotherapy regimes; cytotoxic chemotherapy
• Immunosuppressive mediations (steroids, tumor necrosis factor (TNF)-inhibitors, azathioprine, etc.) within the past 6 weeks
• Active or chronic infection with HIV, hepatitis B or hepatitis C
• WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and 2 weeks after cessation of the study drug.
• Prisoners or subjects who are compulsorily detained

data will not be shared

14 days

Subjects receiving intervention will have adverse events (AEs) recorded during the 14 day course of self-administrated GM-CSF. Subjects will be provided a diary to record any AEs. Subjects will be provided a list of AEs and to call immediately for any grade 3 or high AEs. Grade I-II AEs will be logged into their diary. Diary will be collected the day of surgery. All-Cause Mortality, Serious, and Other (Not Including Serious) AEs were not monitored/assessed for the Standard of Care Arm/Group.