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

Study Overview
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Brief Summary
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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.

Detailed Description
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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 ml saline GM-CSF in 1 ml saline an emulsion of Montanide ISA-51 adjuvant and saline 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.

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

Conditions
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Melanoma

Intervention / Treatment
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* Drug: GM-CSF-in-adjuvant
* Drug: Montanide ISA-51
* Biological: GM-CSF and Montanide ISA-51
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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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: Karnofsky performance of 80% or higher ECOG performance status of 0 or 1 Ability and willingness to give informed consent Laboratory parameters as follows: ANC: 90% of lower limit of normal (LLN) to 120% of upper limit of normal (ULN) Platelets: 100-500 x 103/uL Hgb: 90% LLN to 120% ULN Hepatic: AST, ALT, Bilirubin, and Alk phos within normal limits, LDH up to 1.2 x ULN Renal: 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Saline<br>first of 4 arms: injection: 1 ml saline | Drug: Saline<br>* For each injection, patients will receive the following: In stage 1: Patients will be injected with a 1 ml emulsion of specified dose of GM-CSF in 0.5 ml saline plus 0.5 ml 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 at one of two time points: 1 ml saline specified dose of GM-CSF in 1 ml saline an emulsion of 0.5ml Montanide ISA-51 adjuvant and 0.5 ml saline an emulsion of specified dose of GM-CSF in 0.5 ml saline plus 0.5 ml Montanide ISA-51 adjuvant<br>|
| Active Comparator: GM-CSF<br>Second of 4 arms: injection: specified dose of GM-CSF in 1 ml saline | Drug: GM-CSF-in-adjuvant<br>* For each injection, patients will receive the following: In stage 1: Patients will be injected with a 1 ml emulsion of specified dose of GM-CSF in 0.5 ml saline plus 0.5 ml 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 at one of two time points: 1 ml saline specified dose of GM-CSF in 1 ml saline an emulsion of 0.5ml Montanide ISA-51 adjuvant and 0.5 ml saline an emulsion of specified dose of GM-CSF in 0.5 ml saline plus 0.5 ml Montanide ISA-51 adjuvant<br>|
| Active Comparator: 0.5 ml Montanide ISA-51 adjuvant and 0.5 ml saline<br>Third of 4 arms: injection: 0.5 ml Montanide ISA-51 adjuvant and 0.5 ml saline | Drug: Montanide ISA-51<br>* For each injection, patients will receive the following: In stage 1: Patients will be injected with a 1 ml emulsion of specified dose of GM-CSF in 0.5 ml saline plus 0.5 ml 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 at one of two time points: 1 ml saline specified dose of GM-CSF in 1 ml saline an emulsion of 0.5ml Montanide ISA-51 adjuvant and 0.5 ml saline an emulsion of specified dose of GM-CSF in 0.5 ml saline plus 0.5 ml Montanide ISA-51 adjuvant<br>|
| Active Comparator: GM-CSF in 0.5 ml slaine plus 0.5 ml Montanide ISA-51 adjuvant<br>Fourth of 4 arms: injection: specified dose of GM-CSF in 0.5 ml slaine plus 0.5 ml Montanide ISA-51 adjuvant | Biological: GM-CSF and Montanide ISA-51<br>* For each injection, patients will receive the following: In stage 1: Patients will be injected with a 1 ml emulsion of specified dose of GM-CSF in 0.5 ml saline plus 0.5 ml 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 at one of two time points: 1 ml saline specified dose of GM-CSF in 1 ml saline an emulsion of 0.5ml Montanide ISA-51 adjuvant and 0.5 ml saline an emulsion of specified dose of GM-CSF in 0.5 ml saline plus 0.5 ml Montanide ISA-51 adjuvant<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of dendritic cells (total and mature) accumulating in the dermis after administration of the adjuvant |  |  | 
| Proportion of the sentinel node occupied by dendritic cells (total and mature) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to maximal dendritic cell infiltration into the dermis |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Melanoma, adjuvant, dendritic cells, vaccine