IL15 Dendritic Cell Vaccine for Patients With Resected Stage III (A, B or C) or Stage IV Melanoma

Study Overview
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Brief Summary
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The purpose of the study is to gather data on feasibility as well as immune and clinical efficacy of of a dendritic cell vaccine using IL15 in patients with resected stage III or stage IV melanoma

Detailed Description
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IL15 is a T cell growth factor that pre-clinical data overwhelmingly suggests could have a very important role in cancer immunotherapy. A desirable property for a dendritic cell vaccine directed against cancer is the ability to efficiently prime naïve, tumor associated antigen specific T cells into potent CTLs. Results of studies in healthy volunteers have shown that IL15 DCs are particularly efficient at priming functional melanoma specific CD8+ T cells. The use of IL15 in the manufacture of the DC vaccine could result in an improved immunotherapy product.

Official Title
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IL15-DC Vaccine in Patients With High Risk Melanoma - Exploratory Phase I/II Trial

Conditions
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Malignant Melanoma Stage III, Malignant Melanoma Stage IV

Intervention / Treatment
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* Biological: IL15-DC Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HLA A201 + phenotype Biopsy-proven melanoma, Stages III (A, B and C) or stage IV.- no evidence of disease at study entry Age: 21-75 years ECOG performance status 0-1 Adequate marrow function Adequate hepatic function Adequate renal function Written informed consent Exclusion Criteria: Subjects with measureable non-resectable melanoma Subjects who have had chemotherapy less than 4 weeks before starting trial Subjects who received IFN-a or GM-CSF less than 4 weeks before starting trial Subjects who received IL2 less than 4 weeks before starting trial Subjects with a baseline LDH greater than 1.1 times the ULN Subjects who are HIV positive Female subjects who are pregnant Subjects who have received corticosteroids or other immunosuppressive agents less than 4 weeks before starting trial Subjects who have asthma and/or are on treatment for asthma Subjects with angina pectoris Subjects with congestive heart failure Subjects with history of autoimmune disease including lupus, rheumatoid arthritis or thyroiditis Subjects with active infections including viral hepatitis Subjects with a history of neoplastic disease othe than melanoma within the last 5 years History of neoplastic disease within the last 5 years except for carcinoma in situ of the cervix, superficial bladder cancer or basal/squamous cell carcinoma of the skin. Subjects who present with open wounds

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IL15-DC Vaccine<br>Approximately 9 x 10^6 DCs will be injected (subcutaneously)total per vaccination visit. Patients will receive four vaccinations at weeks 0, 4, 8 and 12.At each scheduled vaccination the patient will receive a total of 3 injections, i.e., 3 mL injections at each of 3 anatomical locations.Injection sites are in upper and lower extremities. Subsequent DC injections will be rotated to different locations on the upper and lower extremities. | Biological: IL15-DC Vaccine<br>* Autologous dendritic cells manufactured with GM-CSF, IL15 and loaded with melanoma/HIV peptides and KLH; then activated with LPS and CD40 Ligand. Approximately 9 x 10^6 DCs will be injected (subcutaneously)total per vaccination visit. Patients will receive four vaccinations at weeks 0, 4, 8 and 12. At each scheduled vaccination the patient will receive a total of 3 injections, i.e., 3 mL injections at each of 3 anatomical locations.Injection sites are in upper and lower extremities. Subsequent DC injections will be rotated to different locations on the upper and lower extremities.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune response |  | 14 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of elicited melanoma specific CD8+ T cells |  | 14 weeks | 
| Breadth of melanoma specific immunity |  | 24 weeks | 
| Longevity of melanoma specific CD8+ T cell immunity |  | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Melanoma, Vaccine, Dendritic Cell, Immune response, Safety, Efficacy