Dendritic Cell Based Therapy of Malignant Melanoma

Study Overview
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Brief Summary
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The aim of the study is to show if vaccination with autologous dendritic cells pulsed with peptides or tumor lysate in combination with adjuvant cytokines and Cyclophosphamide can induce a measurable immune response in patients with metastatic malignant melanoma, and to evaluate the clinical effect (objective response rate) of the vaccination regime.

Detailed Description
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Eligible patients receive vaccination with tumor antigen pulsed autologous monocyte-derived mature dendritic cells with a fixed interval. The dendritic cells are generated from leukapheresis products and frozen after antigen loading. HLA A2 positive patients are treated with PADRE and oncopeptide pulsed DC; p53, survivin and telomerase peptides. HLA A2 negative patients are treated with KLH and tumorlysate pulsed DC; autologous or allogeneic. Each patient is given 6 immunizations with at least 5x106 peptide/lysate pulsed autologous DC. Vaccination 1-4 is given weekly and 4-6 at 2-week intervals. Those patients who exhibit stable disease, partial response or complete response after 6 injections will be given 4 more vaccinations at 2-week interval. The vaccine is applied by intradermal injection near the inguinal region. IL-2 2 MIU s.c. day 2-6, Cyclophosphamide (Sendoxan®, Baxter A/S) 50 mg twice a day bi-weekly and 200 mg Celecoxib (Celebra®, Pfizer) daily are used. Scans and re-staging tests are performed at scheduled intervals throughout the study.

Official Title
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Vaccination With Autologous Dendritic Cells Pulsed With Tumor Antigens for Treatment of Patients With Malignant Melanoma. Phase I/II Study

Conditions
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Advanced Melanoma

Intervention / Treatment
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* Biological: tumor antigen loaded autologous dendritic cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven progressive metastatic or locally advanced melanoma No standard treatment indicated Age: > 18 WHO-Performance Status 0-1 At least tone measurable tumor lesions according to the RECIST criteria. Life expectancy more than 3 months Acceptable CBC and blood chemistry results Written informed consent Exclusion Criteria: Patients with a history of any other neoplastic disease less than 5 years ago (excepting treated carcinomas in situ of the cervix and basal/squamous cell carcinomas of the skin). Patients with metastatic disease in the central nervous system (CNS). Patients with other significant illness including severe allergy, asthma, angina pectoris or congestive heart failure. Patients with acute or chronic infection including HIV, hepatitis and tuberculosis. Patients who are pregnant. Patients who have received antineoplastic therapy including chemotherapy or immunotherapy less than 4 weeks before beginning the trial. Patients who receive corticosteroids or other immunosuppressive agents. Baseline serum LDH greater than 2.5 times the upper limit of normal. Patients with active autoimmune diseases such as lupus erythematosus, rheumatoid arthritis or thyroiditis.

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: tumor antigen loaded autologous dendritic cells|DC vaccination regime consists of primary 10 intradermal injections of 1-2 weeks interval (q1w x 4 → q2w x 6). HLA-A2 positive patients are treated with p53, survivin and telomerase peptide-pulsed dendritic cells, and HLA-A2 negative patients are treated with allogeneic tumor lysate pulsed dendritic cells. 50 mg cyclophosphamide (Sendoxan®, Baxter A/S) is administered p.o. twice a day bi-weekly and 200 mg celecoxib (Celebra®, Pfizer) is given p.o. every day. From the 2nd vaccine, 2 MIU Interleukin-2 is administered s.c. on day 2-6.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary aim of the study is to evaluate tolerability and safety of the treatment |  | weekly the first four weeks thereafter biweekly | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary aims: evaluation of treatment induced immune response and clinical response. |  | after 8 and 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dendritic cell, cancer vaccine, cyclophosphamide, melanoma