E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Our study population consists of HLA-A2.1 positive patients with a high risk uveal melanoma (stage II) with proven expression of melanoma associated antigens tyrosinase and/or gp100. Patients are identified as high risk due to their genetic profile, i.e. loss of chromosome 3. Patients are included within 12 months after local treatment. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The first objective is to study the efficacy of autologous mRNA-transfected monocyte-derived DC in terms of progression free survival (PFS) in high-risk uveal melanoma patients. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are: • to study the toxicity of mRNA-transfected DC injected i.d./i.v and • to study the in vivo immunological response to this treatment Toxicity will be assessed using the Clinical Toxicity Criteria NCI CTC version 3.0. The in vivo immunological response will be assessed as: - proliferative and humoral response to KLH - cytokine production of KLH stimulated PBMC - tumor antigen-specific T cell responses in peripheral blood - tumor antigen-specific T cell responses in biopsies from DTH - cytokine production of T cells in biopsies from DTH - cytotoxicity of T cells in biopsies from DTH - immunohistochemical characterization of DTH infiltrating lymphocytes
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- histologically documented evidence of uveal melanoma - HLA-A2.1 phenotype is required - melanoma expressing gp100 (compulsory) and tyrosinase (non-compulsory) - high risk genetic profile (loss of chromosome 3) as determined by FISH - interval since local treatment of uveal melanoma is <12 months - no signs of liver metastasis as determined by diagnostic CT-scan abdomen - normal serum LDH - WBC >3.0×109/l, lymphocytes >0.8×109/l, platelets >100×109/l, serum crea-tinine <150 µmol/l, serum bilirubin <25 µmol/l - no clinical signs of CNS metastases - WHO performance status 0-1 (Karnofsky 100-70%) - life expectancy >3 months - age 18-75 years - expected adequacy of follow-up - no pregnant or lactating women - written informed consent
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E.4 | Principal exclusion criteria |
- history of second malignancy, adequately treated basal cell carcinoma or carcinoma in situ of the cervix is acceptable - serious active infections, HbsAg or HIV positive - autoimmune diseases or organ allografts - concomitant use of immunosuppressive drugs - known allergy to shell fish (since it contains KLH)
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is progression-free survival determined as no signs of disease. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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After the last visit of the last subject undergoing the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |