{
    "info": {
        "nct_id": "NCT04214860",
        "official_title": "Phase I Study of APR-246 in Combination With Venetoclax and Azacitidine in TP53-Mutant Myeloid Malignancies",
        "inclusion_criteria": "1. Signed informed consent and ability to comply with protocol requirements.\n2. Documented diagnosis of AML according to World Health Organization WHO) classification\n3. Adequate organ function as defined by the following laboratory values:\n\n   1. Creatinine clearance > 30 mL/min\n   2. Total serum bilirubin < 1.5 × ULN\n   3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 × ULN\n4. Age ≥18 years\n5. At least one TP53 mutation\n6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2\n7. Projected life expectancy of ≥ 12 weeks.\n8. Negative serum or urine pregnancy test\n9. Females of childbearing potential and males with female partners of childbearing potential must be willing to use an effective form of contraception\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "1. Prior treatment for TP53-mutant AML (*dependent upon treatment arm assigned).\n2. Known history of HIV or active hepatitis B or active hepatitis C infection.\n3. Any of the following cardiac abnormalities:\n\n   1. Myocardial infarction within six months prior to registration;\n   2. New York Heart Association Class III or IV heart failure or known left ventricular ejection fraction (LVEF) < 40%;\n   3. A history of familial long QT syndrome;\n   4. Symptomatic atrial or ventricular arrhythmias\n   5. QTcF ≥ 470 msec, unless due to underlying bundle branch block and/or pacemaker and with approval of the medical monitor.\n4. Concomitant malignancies for which patients are receiving active therapy\n5. Known active CNS involvement from AML.\n6. Malabsorption syndrome\n7. Pregnancy or lactation.\n8. Active uncontrolled systemic infection (viral, bacterial or fungal).",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Signed informed consent and ability to comply with protocol requirements.",
            "criterions": [
                {
                    "exact_snippets": "Signed informed consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "signed",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "ability to comply with protocol requirements",
                    "criterion": "protocol compliance",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Documented diagnosis of AML according to World Health Organization WHO) classification",
            "criterions": [
                {
                    "exact_snippets": "Documented diagnosis of AML according to World Health Organization WHO) classification",
                    "criterion": "AML diagnosis",
                    "requirements": [
                        {
                            "requirement_type": "documentation",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "classification",
                            "expected_value": "World Health Organization (WHO) classification"
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Adequate organ function as defined by the following laboratory values:",
            "criterions": [
                {
                    "exact_snippets": "Adequate organ function",
                    "criterion": "organ function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Creatinine clearance > 30 mL/min",
            "criterions": [
                {
                    "exact_snippets": "Creatinine clearance > 30 mL/min",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">",
                                "value": 30,
                                "unit": "mL/min"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Total serum bilirubin < 1.5 × ULN",
            "criterions": [
                {
                    "exact_snippets": "Total serum bilirubin < 1.5 × ULN",
                    "criterion": "total serum bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 1.5,
                                "unit": "× ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Age ≥18 years",
            "criterions": [
                {
                    "exact_snippets": "Age ≥18 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. At least one TP53 mutation",
            "criterions": [
                {
                    "exact_snippets": "At least one TP53 mutation",
                    "criterion": "TP53 mutation",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "mutation"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": [
                                "0",
                                "1",
                                "2"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Projected life expectancy of ≥ 12 weeks.",
            "criterions": [
                {
                    "exact_snippets": "Projected life expectancy of ≥ 12 weeks.",
                    "criterion": "projected life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Negative serum or urine pregnancy test",
            "criterions": [
                {
                    "exact_snippets": "Negative serum or urine pregnancy test",
                    "criterion": "pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        },
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "serum",
                                "urine"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Females of childbearing potential and males with female partners of childbearing potential must be willing to use an effective form of contraception",
            "criterions": [
                {
                    "exact_snippets": "Females of childbearing potential",
                    "criterion": "females of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "willingness to use contraception",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "males with female partners of childbearing potential",
                    "criterion": "males with female partners of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "willingness to use contraception",
                            "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"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "1. Prior treatment for TP53-mutant AML (*dependent upon treatment arm assigned).",
            "criterions": [
                {
                    "exact_snippets": "Prior treatment for TP53-mutant AML",
                    "criterion": "prior treatment for TP53-mutant AML",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Known history of HIV or active hepatitis B or active hepatitis C infection.",
            "criterions": [
                {
                    "exact_snippets": "Known history of HIV",
                    "criterion": "HIV infection",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "active hepatitis B",
                    "criterion": "hepatitis B infection",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "active hepatitis C infection",
                    "criterion": "hepatitis C infection",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Any of the following cardiac abnormalities:",
            "criterions": [
                {
                    "exact_snippets": "cardiac abnormalities",
                    "criterion": "cardiac abnormalities",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Myocardial infarction within six months prior to registration;",
            "criterions": [
                {
                    "exact_snippets": "Myocardial infarction within six months prior to registration",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. New York Heart Association Class III or IV heart failure or known left ventricular ejection fraction (LVEF) < 40%;",
            "criterions": [
                {
                    "exact_snippets": "New York Heart Association Class III or IV heart failure",
                    "criterion": "New York Heart Association heart failure class",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "Class III",
                                "Class IV"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "known left ventricular ejection fraction (LVEF) < 40%",
                    "criterion": "left ventricular ejection fraction (LVEF)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<",
                                "value": 40,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. A history of familial long QT syndrome;",
            "criterions": [
                {
                    "exact_snippets": "A history of familial long QT syndrome",
                    "criterion": "familial long QT syndrome",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Symptomatic atrial or ventricular arrhythmias",
            "criterions": [
                {
                    "exact_snippets": "Symptomatic atrial or ventricular arrhythmias",
                    "criterion": "atrial arrhythmias",
                    "requirements": [
                        {
                            "requirement_type": "symptomatic",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Symptomatic atrial or ventricular arrhythmias",
                    "criterion": "ventricular arrhythmias",
                    "requirements": [
                        {
                            "requirement_type": "symptomatic",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. QTcF ≥ 470 msec, unless due to underlying bundle branch block and/or pacemaker and with approval of the medical monitor.",
            "criterions": [
                {
                    "exact_snippets": "QTcF ≥ 470 msec",
                    "criterion": "QTcF interval",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 470,
                                "unit": "msec"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "unless due to underlying bundle branch block",
                    "criterion": "underlying bundle branch block",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "unless due to ... pacemaker",
                    "criterion": "pacemaker",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "with approval of the medical monitor",
                    "criterion": "approval of the medical monitor",
                    "requirements": [
                        {
                            "requirement_type": "approval",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Concomitant malignancies for which patients are receiving active therapy",
            "criterions": [
                {
                    "exact_snippets": "Concomitant malignancies",
                    "criterion": "concomitant malignancies",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "patients are receiving active therapy",
                    "criterion": "active therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Known active CNS involvement from AML.",
            "criterions": [
                {
                    "exact_snippets": "Known active CNS involvement from AML",
                    "criterion": "CNS involvement from AML",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "active"
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Malabsorption syndrome",
            "criterions": [
                {
                    "exact_snippets": "Malabsorption syndrome",
                    "criterion": "malabsorption syndrome",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Pregnancy or lactation.",
            "criterions": [
                {
                    "exact_snippets": "Pregnancy",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "lactation",
                    "criterion": "lactation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Active uncontrolled systemic infection (viral, bacterial or fungal).",
            "criterions": [
                {
                    "exact_snippets": "Active uncontrolled systemic infection (viral, bacterial or fungal)",
                    "criterion": "systemic infection",
                    "requirements": [
                        {
                            "requirement_type": "control status",
                            "expected_value": "uncontrolled"
                        },
                        {
                            "requirement_type": "activity status",
                            "expected_value": "active"
                        },
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "viral",
                                "bacterial",
                                "fungal"
                            ]
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "line": "3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 × ULN",
            "criterions": [
                {
                    "exact_snippets": "Alanine aminotransferase (ALT) < 3 × ULN",
                    "criterion": "Alanine aminotransferase (ALT)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 3,
                                "unit": "× ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "aspartate aminotransferase (AST) < 3 × ULN",
                    "criterion": "aspartate aminotransferase (AST)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 3,
                                "unit": "× ULN"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}