Adenovirus CCL-21 Transduced MART-1/gp100/Tyrosinase/NY-ESO-1 Peptide-Pulsed Dendritic Cells Matured

Study Overview
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Brief Summary
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RATIONALE: Vaccines made from gene-modified tumor cells may help the body build an immune response to kill tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy in treating patients with metastatic melanoma.

Detailed Description
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In this phase I study, patients will receive intradermal injections of adenovirus-CCL-21 transduced class I peptide-pulsed DC with total volumes for each intradermal injection of no more than 1 ml to be split into four injections of 0.25 ml each in four limbs in node draining areas (proximal arms and thighs), for a total DC dose of 2 X 10^6, 10^7 or 2 X 10^7 cells to be administered intradermally. DC injections in one course of therapy will be given four times at intervals of weekly for two doses (days 1 and 8 +/- 72 hrs.), then every two weeks for two doses (at days 22 +/- 72 hrs. and 36 +/- 72 hours). Cells will be harvested for DC administration and a flow cytometry analysis as well as microbiologic analysis including bacterial/fungal cultures and gram stain will be performed prior to infusion. All injections will be based on number of DC, not number of total cells.

Official Title
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A Dose Ranging Trial of Adenovirus CCL-21 Transduced MART-1/gp100 Peptide-Pulsed Dendritic Cells Matured Using Cytokines for Patients With Chemotherapy-Resistant Metastatic Melanoma

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: Autologous dendritic cell-adenovirus CCL21 vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Metastatic melanoma with measurable disease after attempted curative surgical therapy and who have received at least one prior chemotherapy regimen; adjuvant interferon or isolated limb perfusion is allowed. Tumor tissue must be available for immunohistochemical analysis, and specimens will stained for MART-1 by immunohistochemical staining and will also be stained for HMB-45 by immunohistochemistry, and positivity for at least one will be an entry requirement. Patients must be HLA-A *0201 positive, by a DNA SSOP analysis. Serum creatinine of 2.0 mg/dl or less, total bilirubin of 2.0 mg/dl or less, and ALT/AST of less than 3X institutional upper limit of normal. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Patients must be able to understand and sign an IRB approved informed consent form. Patients must have white blood count of 3000 or greater, platelets of 100,000 or greater, and hemoglobin of 9.0 gm/dl or more. Patients with unresectable stages III/IV uveal melanoma and metastatic mucosal melanoma will be eligible for this trial. Exclusion Criteria: Undergoing or have undergone in the past month any other therapy for their melanoma, including radiation therapy, chemotherapy and adjuvant therapy Have major systemic infections, coagulation disorders, or other major medical illnesses of the cardiovascular or respiratory systems, or have had a documented MI in the last 6 months Require steroid therapy Patients who are pregnant or lactating Known to be positive for hepatitis BsAg, Hepatitis C or HIV antibody Have a prior history of uveitis or autoimmune inflammatory eye disease Have had another malignancy other than cervical carcinoma-in-situ or basal cell /squamous cancer of the skin, unless they have undergone curative therapy more than 3 years ago and are still free of detectable disease, since the effects of peptide-pulsed DC on other active cancers are unknown

Ages Eligible for Study
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Minimum Age: 18 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: Vaccine Dose Escalation<br>Dose Escalation: Intradermal DC Injection. Level 1: Cell Dose: 2 x 10^6 Level 2: Cell Dose: 1 x 10^7 Level 3: Cell Dose: 2 x 10^7 | Biological: Autologous dendritic cell-adenovirus CCL21 vaccine<br>* Intradermal injections of adenovirus-CCL-21 transduced class I peptide-pulsed DC<br>* Other names: dendritic cell (DC);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Immune response | Assessment of immune responses to the cytokine-cocktail-matured class I peptide-pulsed adenoviral CCL-21 transduced DC cell vaccine. Immune reactivity will be monitored for the appearance of lymphoid-like structures at the vaccine site (as a result of CCL-21 production), in the blood for MART-1 /gp100 specific T cell frequency by tetramer based flow cytometry and ELISPOT analysis of fresh cells, and CTL cytolytic reactivity after in vitro sensitization prior to, four weeks after, and 8 weeks after immunization. | 2 years, 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events | Toxicity as assessed by NCI CTCAE v3.0 | 2 years, 5 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III melanoma, stage IV melanoma, recurrent melanoma, mucosal melanoma