{
    "info": {
        "nct_id": "NCT05620862",
        "official_title": "Phase I Dose Escalation and Pharmacokinetics Clinical Trial of Mitoxantrone Hydrochloride Liposome in Children With Relapsed and Refractory Lymphoma and Solid Tumors",
        "inclusion_criteria": "* 1. Subjects fully understand and voluntarily participate in this study and sign the informed consent form (ICF);\n* 2. 2-21 years old;\n* 3. Expected survival ≥ 3 months;\n* 4. Subjects with histologically confirmed diagnosis of relapsed and refractory lymphoma and solid tumors, which is one of the following subtypes:\n\n  1. Lymphoblastic lymphoma\n  2. Anaplastic large T cell lymphoma\n  3. Burkitt's lymphoma\n  4. Diffuse large B-cell lymphoma\n  5. Peripheral T, NK/T cell lymphoma\n  6. Soft tissue sarcoma\n  7. Neuroblastoma\n  8. Other subtypes of lymphoma or solid tumors that the investigators believe can be included\n* 5. Relapsed lymphoma is defined as the lymphoma that relapse after obtaining complete response (CR) after initial chemotherapy; Refractory lymphoma subjects meet one of the following conditions: 1) The tumor shrinks <50% or disease progression after 4 cycles of standard chemotherapy,; 2) CR after standard chemotherapy, but relapse within half a year; 3) 2 or more relapses after CR; 4) relapse after hematopoietic stem cell transplantation;\n* 6. Lymphoma subjects must have at least one evaluable or measurable lesion per lugano2014 criteria: for lymph node lesions, the length should be > 1.5cm; For non-lymph node lesions, the length should be > 1.0cm;\n* 7. Solid tumors must have tumor lesions measurable by CT or MRI;\n* 8. ECOG Performance Status: 0-2;\n* 9. Bone marrow function: Absolute neutrophil count ≥1.5×109/L, Platelet count ≥75×109/L, Hemoglobin ≥ 80g/L (Absolute neutrophil can be relaxed to ≥ 1.0×109/L, Platelet count can be relaxed to ≥50×109/L, Hemoglobin can be relaxed to ≥75 g/L in subjects with poor bone-marrow reserve);\n* 10. Liver and kidney function: serum creatinine ≤ 1.5×ULN (upper limit of normal); AST and ALT ≤ 2.5×ULN (≤ 5×ULN for subjects with liver metastases); total bilirubin ≤ 1.5×ULN (≤ 3×ULN for subjects with liver metastases).\nHealthy volunteers allowed\nMust have minimum age of 2 Years\nMust have maximum age of 21 Years",
        "exclusion_criteria": "* 1. The subject had previously received any of the following anti-tumor treatments:\n\n  1. Subjects who have been treated with mitoxantrone or mitoxantrone liposomes;\n  2. Previously received doxorubicin or other anthracycline treatment, and the total cumulative dose of doxorubicin was more than 360 mg/m2 (1 mg doxorubicin equivalent to 2 mg epirubicin);\n  3. Subjects who received anti-tumor treatment (including chemotherapy, targeted therapy, glucocorticoid, traditional Chinese medicine with anti-tumor activity, etc.) or participated in other clinical trials and received trial drugs;\n  4. Subjects who received autologous hematopoietic stem cell transplantation within 100 days after the first medication or allogeneic hematopoietic stem cell transplantation.\n* 2. Hypersensitivity to any study drug or its components;\n* 3. Uncontrolled systemic diseases (such as active infection, uncontrolled hypertension, diabetes, etc.);\n* 4. Heart function and disease meet one of the following conditions:\n\n  1. Long QTc syndrome or QTc interval > 480 ms;\n  2. Complete left bundle branch block, grade II or III atrioventricular block;\n  3. Serious and uncontrolled arrhythmias requiring drug treatment;\n  4. New York Heart Association grade ≥ III;\n  5. Cardiac ejection fraction (LVEF)< 50%;\n  6. A history of myocardial infarction, unstable angina pectoris, severe unstable ventricular arrhythmia or any other arrhythmia requiring treatment, a history of clinically serious pericardial disease, or ECG evidence of acute ischemia or active conduction system abnormalities within 6 months before recruitment.\n* 5. Hepatitis B and hepatitis C active infection (plus HBV DNA if one positive for hepatitis B surface antigen or core antibody and HBV DNA more than 1×103 copy/mL excluded; plus HCV RNA if hepatitis C antibody positive and HCV RNA more than 1×103 copy/mL exclude);\n* 6. Human immunodeficiency virus (HIV) infection (HIV antibody positive);\n* 7. Subjects with other malignant tumors past or present (except for non-melanoma skin basal cell carcinoma, breast/cervical carcinoma in control, and other malignant tumors that have been effectively controlled without treatment within the past five years);\n* 8. Subjects suffering from primary or secondary central nervous system (CNS) lymphoma or a history of CNS lymphoma at the time of recruitment;\n* 9. Pregnant and lactating women and childbearing age patients unwilling to take contraceptive measures;\n* 10. Unsuitable subjects for this study determined by the investigator.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* 1. Subjects fully understand and voluntarily participate in this study and sign the informed consent form (ICF);",
            "criterions": [
                {
                    "exact_snippets": "Subjects fully understand",
                    "criterion": "understanding of the study",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "voluntarily participate in this study",
                    "criterion": "voluntary participation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "sign the informed consent form (ICF)",
                    "criterion": "informed consent form",
                    "requirements": [
                        {
                            "requirement_type": "signed",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 2. 2-21 years old;",
            "criterions": [
                {
                    "exact_snippets": "2-21 years old",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 2,
                                        "unit": "years"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 21,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 3. Expected survival ≥ 3 months;",
            "criterions": [
                {
                    "exact_snippets": "Expected survival ≥ 3 months",
                    "criterion": "expected survival",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 4. Subjects with histologically confirmed diagnosis of relapsed and refractory lymphoma and solid tumors, which is one of the following subtypes:",
            "criterions": [
                {
                    "exact_snippets": "histologically confirmed diagnosis of relapsed and refractory lymphoma",
                    "criterion": "relapsed and refractory lymphoma",
                    "requirements": [
                        {
                            "requirement_type": "diagnosis",
                            "expected_value": "histologically confirmed"
                        }
                    ]
                },
                {
                    "exact_snippets": "histologically confirmed diagnosis of ... solid tumors",
                    "criterion": "solid tumors",
                    "requirements": [
                        {
                            "requirement_type": "diagnosis",
                            "expected_value": "histologically confirmed"
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Lymphoblastic lymphoma",
            "criterions": [
                {
                    "exact_snippets": "Lymphoblastic lymphoma",
                    "criterion": "lymphoblastic lymphoma",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Anaplastic large T cell lymphoma",
            "criterions": [
                {
                    "exact_snippets": "Anaplastic large T cell lymphoma",
                    "criterion": "anaplastic large T cell lymphoma",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Burkitt's lymphoma",
            "criterions": [
                {
                    "exact_snippets": "Burkitt's lymphoma",
                    "criterion": "Burkitt's lymphoma",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Diffuse large B-cell lymphoma",
            "criterions": [
                {
                    "exact_snippets": "Diffuse large B-cell lymphoma",
                    "criterion": "diffuse large B-cell lymphoma",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Peripheral T, NK/T cell lymphoma",
            "criterions": [
                {
                    "exact_snippets": "Peripheral T, NK/T cell lymphoma",
                    "criterion": "lymphoma type",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "Peripheral T cell lymphoma",
                                "NK/T cell lymphoma"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Soft tissue sarcoma",
            "criterions": [
                {
                    "exact_snippets": "Soft tissue sarcoma",
                    "criterion": "soft tissue sarcoma",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Neuroblastoma",
            "criterions": [
                {
                    "exact_snippets": "Neuroblastoma",
                    "criterion": "neuroblastoma",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Other subtypes of lymphoma or solid tumors that the investigators believe can be included",
            "criterions": [
                {
                    "exact_snippets": "Other subtypes of lymphoma or solid tumors",
                    "criterion": "subtypes of lymphoma or solid tumors",
                    "requirements": [
                        {
                            "requirement_type": "inclusion",
                            "expected_value": "investigators believe can be included"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 5. Relapsed lymphoma is defined as the lymphoma that relapse after obtaining complete response (CR) after initial chemotherapy; Refractory lymphoma subjects meet one of the following conditions: 1) The tumor shrinks <50% or disease progression after 4 cycles of standard chemotherapy,; 2) CR after standard chemotherapy, but relapse within half a year; 3) 2 or more relapses after CR; 4) relapse after hematopoietic stem cell transplantation;",
            "criterions": [
                {
                    "exact_snippets": "Relapsed lymphoma is defined as the lymphoma that relapse after obtaining complete response (CR) after initial chemotherapy",
                    "criterion": "relapsed lymphoma",
                    "requirements": [
                        {
                            "requirement_type": "definition",
                            "expected_value": "relapse after obtaining complete response (CR) after initial chemotherapy"
                        }
                    ]
                },
                {
                    "exact_snippets": "Refractory lymphoma subjects meet one of the following conditions: 1) The tumor shrinks <50% or disease progression after 4 cycles of standard chemotherapy",
                    "criterion": "refractory lymphoma",
                    "requirements": [
                        {
                            "requirement_type": "tumor shrinkage",
                            "expected_value": {
                                "operator": "<",
                                "value": 50,
                                "unit": "%"
                            }
                        },
                        {
                            "requirement_type": "disease progression",
                            "expected_value": "after 4 cycles of standard chemotherapy"
                        }
                    ]
                },
                {
                    "exact_snippets": "Refractory lymphoma subjects meet one of the following conditions: ... 2) CR after standard chemotherapy, but relapse within half a year",
                    "criterion": "refractory lymphoma",
                    "requirements": [
                        {
                            "requirement_type": "relapse",
                            "expected_value": "within half a year after CR following standard chemotherapy"
                        }
                    ]
                },
                {
                    "exact_snippets": "Refractory lymphoma subjects meet one of the following conditions: ... 3) 2 or more relapses after CR",
                    "criterion": "refractory lymphoma",
                    "requirements": [
                        {
                            "requirement_type": "number of relapses",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "relapses"
                            }
                        },
                        {
                            "requirement_type": "condition",
                            "expected_value": "after CR"
                        }
                    ]
                },
                {
                    "exact_snippets": "Refractory lymphoma subjects meet one of the following conditions: ... 4) relapse after hematopoietic stem cell transplantation",
                    "criterion": "refractory lymphoma",
                    "requirements": [
                        {
                            "requirement_type": "relapse",
                            "expected_value": "after hematopoietic stem cell transplantation"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 6. Lymphoma subjects must have at least one evaluable or measurable lesion per lugano2014 criteria: for lymph node lesions, the length should be > 1.5cm; For non-lymph node lesions, the length should be > 1.0cm;",
            "criterions": [
                {
                    "exact_snippets": "Lymphoma subjects must have at least one evaluable or measurable lesion per lugano2014 criteria",
                    "criterion": "evaluable or measurable lesion",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "for lymph node lesions, the length should be > 1.5cm",
                    "criterion": "lymph node lesion length",
                    "requirements": [
                        {
                            "requirement_type": "length",
                            "expected_value": {
                                "operator": ">",
                                "value": 1.5,
                                "unit": "cm"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "For non-lymph node lesions, the length should be > 1.0cm",
                    "criterion": "non-lymph node lesion length",
                    "requirements": [
                        {
                            "requirement_type": "length",
                            "expected_value": {
                                "operator": ">",
                                "value": 1.0,
                                "unit": "cm"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 7. Solid tumors must have tumor lesions measurable by CT or MRI;",
            "criterions": [
                {
                    "exact_snippets": "Solid tumors must have tumor lesions measurable by CT or MRI",
                    "criterion": "tumor lesions",
                    "requirements": [
                        {
                            "requirement_type": "measurability",
                            "expected_value": [
                                "CT",
                                "MRI"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 8. ECOG Performance Status: 0-2;",
            "criterions": [
                {
                    "exact_snippets": "ECOG Performance Status: 0-2",
                    "criterion": "ECOG Performance Status",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 9. Bone marrow function: Absolute neutrophil count ≥1.5×109/L, Platelet count ≥75×109/L, Hemoglobin ≥ 80g/L (Absolute neutrophil can be relaxed to ≥ 1.0×109/L, Platelet count can be relaxed to ≥50×109/L, Hemoglobin can be relaxed to ≥75 g/L in subjects with poor bone-marrow reserve);",
            "criterions": [
                {
                    "exact_snippets": "Absolute neutrophil count ≥1.5×109/L ... can be relaxed to ≥ 1.0×109/L",
                    "criterion": "absolute neutrophil count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 1.5,
                                        "unit": "×10^9/L"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 1.0,
                                        "unit": "×10^9/L"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Platelet count ≥75×109/L ... can be relaxed to ≥50×109/L",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 75,
                                        "unit": "×10^9/L"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 50,
                                        "unit": "×10^9/L"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Hemoglobin ≥ 80g/L ... can be relaxed to ≥75 g/L",
                    "criterion": "hemoglobin",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 80,
                                        "unit": "g/L"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 75,
                                        "unit": "g/L"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 10. Liver and kidney function: serum creatinine ≤ 1.5×ULN (upper limit of normal); AST and ALT ≤ 2.5×ULN (≤ 5×ULN for subjects with liver metastases); total bilirubin ≤ 1.5×ULN (≤ 3×ULN for subjects with liver metastases).",
            "criterions": [
                {
                    "exact_snippets": "serum creatinine ≤ 1.5×ULN",
                    "criterion": "serum creatinine",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "AST and ALT ≤ 2.5×ULN (≤ 5×ULN for subjects with liver metastases)",
                    "criterion": "AST and ALT",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 2.5,
                                        "unit": "ULN"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 5,
                                        "unit": "ULN"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "total bilirubin ≤ 1.5×ULN (≤ 3×ULN for subjects with liver metastases)",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 1.5,
                                        "unit": "ULN"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 3,
                                        "unit": "ULN"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "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 2 Years",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 2 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have maximum age of 21 Years",
            "criterions": [
                {
                    "exact_snippets": "maximum age of 21 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "maximum",
                            "expected_value": {
                                "operator": "<=",
                                "value": 21,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "* 1. The subject had previously received any of the following anti-tumor treatments:",
            "criterions": [
                {
                    "exact_snippets": "previously received any of the following anti-tumor treatments",
                    "criterion": "previous anti-tumor treatments",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Subjects who have been treated with mitoxantrone or mitoxantrone liposomes;",
            "criterions": [
                {
                    "exact_snippets": "treated with mitoxantrone",
                    "criterion": "mitoxantrone treatment",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "treated with ... mitoxantrone liposomes",
                    "criterion": "mitoxantrone liposomes treatment",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Previously received doxorubicin or other anthracycline treatment, and the total cumulative dose of doxorubicin was more than 360 mg/m2 (1 mg doxorubicin equivalent to 2 mg epirubicin);",
            "criterions": [
                {
                    "exact_snippets": "Previously received doxorubicin or other anthracycline treatment",
                    "criterion": "anthracycline treatment",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "total cumulative dose of doxorubicin was more than 360 mg/m2",
                    "criterion": "cumulative dose of doxorubicin",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">",
                                "value": 360,
                                "unit": "mg/m2"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Subjects who received anti-tumor treatment (including chemotherapy, targeted therapy, glucocorticoid, traditional Chinese medicine with anti-tumor activity, etc.) or participated in other clinical trials and received trial drugs;",
            "criterions": [
                {
                    "exact_snippets": "Subjects who received anti-tumor treatment (including chemotherapy, targeted therapy, glucocorticoid, traditional Chinese medicine with anti-tumor activity, etc.)",
                    "criterion": "anti-tumor treatment",
                    "requirements": [
                        {
                            "requirement_type": "receipt",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "participated in other clinical trials and received trial drugs",
                    "criterion": "participation in other clinical trials",
                    "requirements": [
                        {
                            "requirement_type": "participation",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Subjects who received autologous hematopoietic stem cell transplantation within 100 days after the first medication or allogeneic hematopoietic stem cell transplantation.",
            "criterions": [
                {
                    "exact_snippets": "autologous hematopoietic stem cell transplantation within 100 days after the first medication",
                    "criterion": "autologous hematopoietic stem cell transplantation",
                    "requirements": [
                        {
                            "requirement_type": "time since first medication",
                            "expected_value": {
                                "operator": "<=",
                                "value": 100,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "allogeneic hematopoietic stem cell transplantation",
                    "criterion": "allogeneic hematopoietic stem cell transplantation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 2. Hypersensitivity to any study drug or its components;",
            "criterions": [
                {
                    "exact_snippets": "Hypersensitivity to any study drug or its components",
                    "criterion": "hypersensitivity",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 3. Uncontrolled systemic diseases (such as active infection, uncontrolled hypertension, diabetes, etc.);",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled systemic diseases (such as active infection, uncontrolled hypertension, diabetes, etc.)",
                    "criterion": "systemic diseases",
                    "requirements": [
                        {
                            "requirement_type": "control status",
                            "expected_value": "uncontrolled"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 4. Heart function and disease meet one of the following conditions:",
            "criterions": [
                {
                    "exact_snippets": "Heart function and disease",
                    "criterion": "heart function and disease",
                    "requirements": [
                        {
                            "requirement_type": "condition",
                            "expected_value": "meet one of the following conditions"
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Long QTc syndrome or QTc interval > 480 ms;",
            "criterions": [
                {
                    "exact_snippets": "Long QTc syndrome",
                    "criterion": "Long QTc syndrome",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "QTc interval > 480 ms",
                    "criterion": "QTc interval",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 480,
                                "unit": "ms"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Complete left bundle branch block, grade II or III atrioventricular block;",
            "criterions": [
                {
                    "exact_snippets": "Complete left bundle branch block",
                    "criterion": "left bundle branch block",
                    "requirements": [
                        {
                            "requirement_type": "completeness",
                            "expected_value": "complete"
                        }
                    ]
                },
                {
                    "exact_snippets": "grade II or III atrioventricular block",
                    "criterion": "atrioventricular block",
                    "requirements": [
                        {
                            "requirement_type": "grade",
                            "expected_value": [
                                "II",
                                "III"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Serious and uncontrolled arrhythmias requiring drug treatment;",
            "criterions": [
                {
                    "exact_snippets": "Serious and uncontrolled arrhythmias requiring drug treatment",
                    "criterion": "arrhythmias",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "serious"
                        },
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "treatment",
                            "expected_value": "drug treatment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. New York Heart Association grade ≥ III;",
            "criterions": [
                {
                    "exact_snippets": "New York Heart Association grade ≥ III",
                    "criterion": "New York Heart Association grade",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Cardiac ejection fraction (LVEF)< 50%;",
            "criterions": [
                {
                    "exact_snippets": "Cardiac ejection fraction (LVEF)< 50%",
                    "criterion": "cardiac ejection fraction (LVEF)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<",
                                "value": 50,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. A history of myocardial infarction, unstable angina pectoris, severe unstable ventricular arrhythmia or any other arrhythmia requiring treatment, a history of clinically serious pericardial disease, or ECG evidence of acute ischemia or active conduction system abnormalities within 6 months before recruitment.",
            "criterions": [
                {
                    "exact_snippets": "A history of myocardial infarction",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "unstable angina pectoris",
                    "criterion": "unstable angina pectoris",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "severe unstable ventricular arrhythmia",
                    "criterion": "severe unstable ventricular arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "any other arrhythmia requiring treatment",
                    "criterion": "arrhythmia requiring treatment",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "a history of clinically serious pericardial disease",
                    "criterion": "clinically serious pericardial disease",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "ECG evidence of acute ischemia",
                    "criterion": "acute ischemia",
                    "requirements": [
                        {
                            "requirement_type": "ECG evidence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "active conduction system abnormalities",
                    "criterion": "active conduction system abnormalities",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "within 6 months before recruitment",
                    "criterion": "time since condition",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 6. Human immunodeficiency virus (HIV) infection (HIV antibody positive);",
            "criterions": [
                {
                    "exact_snippets": "Human immunodeficiency virus (HIV) infection (HIV antibody positive)",
                    "criterion": "HIV infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 7. Subjects with other malignant tumors past or present (except for non-melanoma skin basal cell carcinoma, breast/cervical carcinoma in control, and other malignant tumors that have been effectively controlled without treatment within the past five years);",
            "criterions": [
                {
                    "exact_snippets": "Subjects with other malignant tumors past or present",
                    "criterion": "other malignant tumors",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "except for non-melanoma skin basal cell carcinoma",
                    "criterion": "non-melanoma skin basal cell carcinoma",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "except for ... breast/cervical carcinoma in control",
                    "criterion": "breast/cervical carcinoma",
                    "requirements": [
                        {
                            "requirement_type": "control status",
                            "expected_value": "in control"
                        }
                    ]
                },
                {
                    "exact_snippets": "except for ... other malignant tumors that have been effectively controlled without treatment within the past five years",
                    "criterion": "other malignant tumors",
                    "requirements": [
                        {
                            "requirement_type": "control status",
                            "expected_value": "effectively controlled without treatment within the past five years"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 8. Subjects suffering from primary or secondary central nervous system (CNS) lymphoma or a history of CNS lymphoma at the time of recruitment;",
            "criterions": [
                {
                    "exact_snippets": "primary or secondary central nervous system (CNS) lymphoma",
                    "criterion": "central nervous system (CNS) lymphoma",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "history of CNS lymphoma",
                    "criterion": "history of central nervous system (CNS) lymphoma",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 9. Pregnant and lactating women and childbearing age patients unwilling to take contraceptive measures;",
            "criterions": [
                {
                    "exact_snippets": "Pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "lactating women",
                    "criterion": "lactation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "childbearing age patients",
                    "criterion": "childbearing age",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "unwilling to take contraceptive measures",
                    "criterion": "contraceptive measures",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 10. Unsuitable subjects for this study determined by the investigator.",
            "criterions": [
                {
                    "exact_snippets": "Unsuitable subjects for this study determined by the investigator",
                    "criterion": "suitability for study",
                    "requirements": [
                        {
                            "requirement_type": "determination",
                            "expected_value": "investigator's discretion"
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [
        {
            "line": "* 5. Hepatitis B and hepatitis C active infection (plus HBV DNA if one positive for hepatitis B surface antigen or core antibody and HBV DNA more than 1×103 copy/mL excluded; plus HCV RNA if hepatitis C antibody positive and HCV RNA more than 1×103 copy/mL exclude);",
            "criterions": [
                {
                    "exact_snippets": "Hepatitis B ... active infection",
                    "criterion": "Hepatitis B infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Hepatitis C active infection",
                    "criterion": "Hepatitis C infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "HBV DNA ... more than 1×103 copy/mL",
                    "criterion": "HBV DNA level",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">",
                                "value": 1000,
                                "unit": "copy/mL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "HCV RNA ... more than 1×103 copy/mL",
                    "criterion": "HCV RNA level",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">",
                                "value": 1000,
                                "unit": "copy/mL"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "failed_miscellaneous": []
}