{
    "info": {
        "nct_id": "NCT01983748",
        "official_title": "A NON-COMMERCIAL, MULTICENTER, RANDOMIZED, TWO-ARMED, OPEN-LABEL PHASE III STUDY TO EVALUATE THE ADJUVANT VACCINATION WITH TUMOR RNA-LOADED AUTOLOGOUS DENDRITIC CELLS VERSUS OBSERVATION OF PATIENTS WITH RESECTED MONOSOMY 3 UVEAL MELANOMA",
        "inclusion_criteria": "* Patients must suffer from melanoma of the uvea (stage T2, T3 and T4 [AJCC TNM grading 2009]).\n* Uveal melanoma must be resected and display a monosomy for chromosome 3 (will be determined by a validated qualitative analysis of loss of heterozygosity). Tumor material has to be stored appropriately in RNAlater solution for RNA preparation.\n* The patient has to be free of detectable tumor at the time point of study enrollment (adjuvant setting), as assessed by clinical inspection, abdominal sonography, chest X-ray and evaluation of the tumor-marker S-100..\n* Patients must have a WHO performance status of 0, 1 or 2 and must be in stable medical condition.\n* Patients must be between 18 and 75 years old and must be able and willing to give informed consent.\n* Women of child-bearing age must have a negative pregnancy test, and must oblige to use effective contraception until at least 4 weeks after the last vaccination.\n* Patients must be willing to get hospitalized for at least 4 hours following vaccination(s), and to cooperate for the whole period of the trial.\n* Patients must have fully recovered from surgery.\n* Signed informed consent\nHealthy volunteers allowed\nMust have minimum age of 18 Years\nMust have maximum age of 75 Years",
        "exclusion_criteria": "* Any other major serious illness [e.g. active systemic infections, immunodeficiency disease, clinically significant heart disease, respiratory disease, bleeding disorders, cancer etc.] or a contraindication to leukapheresis.\n* Evidence for HIV-1, HIV -2, HTLV-1, HBV, or HCV infection.\n* Active autoimmune disease (such as but not limited to Lupus erythematosus, autoimmune thyroiditis or uveitis, multiple sclerosis, inflammatory bowel disease). Vitiligo and pathological laboratory results (autoantibodies) without clinical symptoms are, however, not an exclusion criterion.\n* Previous splenectomy or radiation therapy to the spleen.\n* Patients with organ allografts.\n* Concomitant treatment with chemotherapy, immunotherapy, any investigational drug and paramedical substances. Patients may receive concomitant medications to control symptoms such as analgetics, antihypertensive medication, etc.\n* History of other active malignant neoplasm within the preceding 5 years (excluding non-melanoma skin cancer or carcinoma in situ of the cervix).\n* Organic brain syndrome or significant psychiatric abnormality which would impede informed consent and / or AND preclude participation in the full protocol and follow up.\n* Positive pregnancy test / Pregnancy or lactation. If pregnancy occurs during the course of the trial to female patients in arm A or B, the patient has to be excluded.\n* Detection of metastases. If uveal melanoma metastases appear during the course of the trial, the patient has to be excluded.\n* Lack of compliance of the patient.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Patients must suffer from melanoma of the uvea (stage T2, T3 and T4 [AJCC TNM grading 2009]).",
            "criterions": [
                {
                    "exact_snippets": "melanoma of the uvea",
                    "criterion": "melanoma of the uvea",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "stage T2, T3 and T4 [AJCC TNM grading 2009]",
                    "criterion": "melanoma stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "T2",
                                "T3",
                                "T4"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Uveal melanoma must be resected and display a monosomy for chromosome 3 (will be determined by a validated qualitative analysis of loss of heterozygosity). Tumor material has to be stored appropriately in RNAlater solution for RNA preparation.",
            "criterions": [
                {
                    "exact_snippets": "Uveal melanoma must be resected",
                    "criterion": "uveal melanoma",
                    "requirements": [
                        {
                            "requirement_type": "resection",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "display a monosomy for chromosome 3",
                    "criterion": "chromosome 3",
                    "requirements": [
                        {
                            "requirement_type": "monosomy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Tumor material has to be stored appropriately in RNAlater solution",
                    "criterion": "tumor material",
                    "requirements": [
                        {
                            "requirement_type": "storage",
                            "expected_value": "RNAlater solution"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* The patient has to be free of detectable tumor at the time point of study enrollment (adjuvant setting), as assessed by clinical inspection, abdominal sonography, chest X-ray and evaluation of the tumor-marker S-100..",
            "criterions": [
                {
                    "exact_snippets": "free of detectable tumor",
                    "criterion": "detectable tumor",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "clinical inspection",
                    "criterion": "clinical inspection",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": "clinical inspection"
                        }
                    ]
                },
                {
                    "exact_snippets": "abdominal sonography",
                    "criterion": "abdominal sonography",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": "abdominal sonography"
                        }
                    ]
                },
                {
                    "exact_snippets": "chest X-ray",
                    "criterion": "chest X-ray",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": "chest X-ray"
                        }
                    ]
                },
                {
                    "exact_snippets": "evaluation of the tumor-marker S-100",
                    "criterion": "tumor-marker S-100",
                    "requirements": [
                        {
                            "requirement_type": "evaluation",
                            "expected_value": "tumor-marker S-100"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must have a WHO performance status of 0, 1 or 2 and must be in stable medical condition.",
            "criterions": [
                {
                    "exact_snippets": "WHO performance status of 0, 1 or 2",
                    "criterion": "WHO performance status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": [
                                "0",
                                "1",
                                "2"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "stable medical condition",
                    "criterion": "medical condition",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": "stable"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must be between 18 and 75 years old and must be able and willing to give informed consent.",
            "criterions": [
                {
                    "exact_snippets": "Patients must be between 18 and 75 years old",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 18,
                                        "unit": "years"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 75,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "must be able and willing to give informed consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Women of child-bearing age must have a negative pregnancy test, and must oblige to use effective contraception until at least 4 weeks after the last vaccination.",
            "criterions": [
                {
                    "exact_snippets": "Women of child-bearing age",
                    "criterion": "gender and reproductive status",
                    "requirements": [
                        {
                            "requirement_type": "gender",
                            "expected_value": "female"
                        },
                        {
                            "requirement_type": "reproductive status",
                            "expected_value": "child-bearing age"
                        }
                    ]
                },
                {
                    "exact_snippets": "must have a negative pregnancy test",
                    "criterion": "pregnancy test result",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "must oblige to use effective contraception",
                    "criterion": "contraception usage",
                    "requirements": [
                        {
                            "requirement_type": "usage",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "until at least 4 weeks after the last vaccination",
                    "criterion": "contraception duration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must be willing to get hospitalized for at least 4 hours following vaccination(s), and to cooperate for the whole period of the trial.",
            "criterions": [
                {
                    "exact_snippets": "Patients must be willing to get hospitalized for at least 4 hours following vaccination(s)",
                    "criterion": "hospitalization",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "hours"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients must be willing ... to cooperate for the whole period of the trial",
                    "criterion": "cooperation",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "whole period of the trial"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must have fully recovered from surgery.",
            "criterions": [
                {
                    "exact_snippets": "fully recovered from surgery",
                    "criterion": "recovery from surgery",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "fully recovered"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Signed informed consent",
            "criterions": [
                {
                    "exact_snippets": "Signed informed consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "signed",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have minimum age of 18 Years",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 18 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have maximum age of 75 Years",
            "criterions": [
                {
                    "exact_snippets": "maximum age of 75 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "maximum",
                            "expected_value": {
                                "operator": "<=",
                                "value": 75,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "* Any other major serious illness [e.g. active systemic infections, immunodeficiency disease, clinically significant heart disease, respiratory disease, bleeding disorders, cancer etc.] or a contraindication to leukapheresis.",
            "criterions": [
                {
                    "exact_snippets": "active systemic infections",
                    "criterion": "systemic infections",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "immunodeficiency disease",
                    "criterion": "immunodeficiency disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "clinically significant heart disease",
                    "criterion": "heart disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "clinically significant"
                        }
                    ]
                },
                {
                    "exact_snippets": "respiratory disease",
                    "criterion": "respiratory disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "bleeding disorders",
                    "criterion": "bleeding disorders",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "cancer",
                    "criterion": "cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "contraindication to leukapheresis",
                    "criterion": "contraindication to leukapheresis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Evidence for HIV-1, HIV -2, HTLV-1, HBV, or HCV infection.",
            "criterions": [
                {
                    "exact_snippets": "Evidence for HIV-1",
                    "criterion": "HIV-1 infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "HIV -2",
                    "criterion": "HIV-2 infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "HTLV-1",
                    "criterion": "HTLV-1 infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "HBV",
                    "criterion": "HBV infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "HCV infection",
                    "criterion": "HCV infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Active autoimmune disease (such as but not limited to Lupus erythematosus, autoimmune thyroiditis or uveitis, multiple sclerosis, inflammatory bowel disease). Vitiligo and pathological laboratory results (autoantibodies) without clinical symptoms are, however, not an exclusion criterion.",
            "criterions": [
                {
                    "exact_snippets": "Active autoimmune disease (such as but not limited to Lupus erythematosus, autoimmune thyroiditis or uveitis, multiple sclerosis, inflammatory bowel disease)",
                    "criterion": "active autoimmune disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Vitiligo and pathological laboratory results (autoantibodies) without clinical symptoms are, however, not an exclusion criterion",
                    "criterion": "vitiligo",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "pathological laboratory results (autoantibodies) without clinical symptoms are, however, not an exclusion criterion",
                    "criterion": "pathological laboratory results (autoantibodies) without clinical symptoms",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Previous splenectomy or radiation therapy to the spleen.",
            "criterions": [
                {
                    "exact_snippets": "Previous splenectomy",
                    "criterion": "splenectomy",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "radiation therapy to the spleen",
                    "criterion": "radiation therapy to the spleen",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with organ allografts.",
            "criterions": [
                {
                    "exact_snippets": "Patients with organ allografts",
                    "criterion": "organ allograft",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Concomitant treatment with chemotherapy, immunotherapy, any investigational drug and paramedical substances. Patients may receive concomitant medications to control symptoms such as analgetics, antihypertensive medication, etc.",
            "criterions": [
                {
                    "exact_snippets": "Concomitant treatment with chemotherapy",
                    "criterion": "concomitant chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Concomitant treatment with ... immunotherapy",
                    "criterion": "concomitant immunotherapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Concomitant treatment with ... any investigational drug",
                    "criterion": "concomitant investigational drug",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Concomitant treatment with ... paramedical substances",
                    "criterion": "concomitant paramedical substances",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of other active malignant neoplasm within the preceding 5 years (excluding non-melanoma skin cancer or carcinoma in situ of the cervix).",
            "criterions": [
                {
                    "exact_snippets": "History of other active malignant neoplasm within the preceding 5 years",
                    "criterion": "active malignant neoplasm",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 5,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "excluding non-melanoma skin cancer or carcinoma in situ of the cervix",
                    "criterion": "type of cancer",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": [
                                "non-melanoma skin cancer",
                                "carcinoma in situ of the cervix"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Organic brain syndrome or significant psychiatric abnormality which would impede informed consent and / or AND preclude participation in the full protocol and follow up.",
            "criterions": [
                {
                    "exact_snippets": "Organic brain syndrome",
                    "criterion": "organic brain syndrome",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "significant psychiatric abnormality",
                    "criterion": "psychiatric abnormality",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "significant"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Positive pregnancy test / Pregnancy or lactation. If pregnancy occurs during the course of the trial to female patients in arm A or B, the patient has to be excluded.",
            "criterions": [
                {
                    "exact_snippets": "Positive pregnancy test",
                    "criterion": "pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "positive"
                        }
                    ]
                },
                {
                    "exact_snippets": "Pregnancy or lactation",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Pregnancy or lactation",
                    "criterion": "lactation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Detection of metastases. If uveal melanoma metastases appear during the course of the trial, the patient has to be excluded.",
            "criterions": [
                {
                    "exact_snippets": "Detection of metastases",
                    "criterion": "metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "uveal melanoma metastases appear during the course of the trial",
                    "criterion": "uveal melanoma metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Lack of compliance of the patient.",
            "criterions": [
                {
                    "exact_snippets": "Lack of compliance of the patient",
                    "criterion": "patient compliance",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}