{
    "info": {
        "nct_id": "NCT00672165",
        "official_title": "Phase I Trial of Targeted Atomic Nano-Generators (Actinium-225-Labeled Humanized Anti-CD33 Monoclonal Antibody HuM195) in Patients With Advanced Myeloid Malignancies",
        "inclusion_criteria": "* Patients must have one of the following pathologically confirmed diagnoses:\n* AML in relapse,\n* AML refractory to at least 2 courses of standard induction chemotherapy or one course of high-dose cytarabine-containing induction chemotherapy,\n* CML in accelerated phase or myeloid blast crisis that has progressed after treatment with imatinib and a second generation tyrosine kinase inhibitor (e.g., dasatinib or nilotinib)\n* RAEB with International Prognostic Scoring System (IPSS) score ≥ 2.5, or - CMMOL with IPSS score ≥ 2.5 refractory to or relapsed after a hypomethylating agent (e.g., azacitidine or decitabine) refractory to or relapsed after a hypomethylating agent (e.g., azacitidine or decitabine).\n* Greater than 25% of bone marrow blasts must be CD33 positive.\n* Patients must have a life expectancy of at least 6 weeks and a Karnofsky performance status of ≥ 60%.\n* Adequate renal function as demonstrated by a serum creatinine ≤ 1.5 mg/dl, a creatinine clearance > 60 ml/min, and < 1 gram urinary protein/24 hours.\n* Adequate hepatic function as demonstrated by a bilirubin ≤ 1.5 mg/dl (unless attributable to leukemia or Gilbert's disease) and alkaline phosphatase and AST ≤ 2.5 times the upper limit of normal.\nHealthy volunteers allowed",
        "exclusion_criteria": "* Untreated AML, regardless of prognostic features.\n* Treatment with chemotherapy or biologic therapy within 3 weeks of 225Ac- HuM195 administration. Hydroxyurea is permitted but must be discontinued prior to treatment on study. Patients must have recovered from the effects of previous treatment.\n* Treatment with radiation therapy within 6 weeks of 225Ac-HuM195 administration. Patients must have recovered from the effects of previous treatment.\n* Active serious infections not controlled by antibiotics.\n* Pregnant women or women who are breast-feeding.\n* Concurrent active malignancy requiring therapy.\n* Clinically significant cardiac disease (NY Heart Association Class III or IV)or pulmonary disease.\n* Patients with HLA-compatible donor bone marrow who are immediate candidates for bone marrow transplantation.\n* Patients who are candidates for alternative treatments of known effectiveness.\n* Patients eligible for protocols of higher priority.\n* Patients previously treated with any monoclonal antibody for any reason.\n* Active CNS leukemia\n* Other serious or life-threatening conditions deemed unacceptable by the principal investigator.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Patients must have one of the following pathologically confirmed diagnoses:",
            "criterions": [
                {
                    "exact_snippets": "pathologically confirmed diagnoses",
                    "criterion": "diagnosis",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": "pathologically confirmed"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* AML in relapse,",
            "criterions": [
                {
                    "exact_snippets": "AML in relapse",
                    "criterion": "AML",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "relapse"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* AML refractory to at least 2 courses of standard induction chemotherapy or one course of high-dose cytarabine-containing induction chemotherapy,",
            "criterions": [
                {
                    "exact_snippets": "AML refractory to at least 2 courses of standard induction chemotherapy",
                    "criterion": "AML refractory",
                    "requirements": [
                        {
                            "requirement_type": "treatment courses",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "courses"
                            }
                        },
                        {
                            "requirement_type": "treatment type",
                            "expected_value": "standard induction chemotherapy"
                        }
                    ]
                },
                {
                    "exact_snippets": "AML refractory to ... one course of high-dose cytarabine-containing induction chemotherapy",
                    "criterion": "AML refractory",
                    "requirements": [
                        {
                            "requirement_type": "treatment courses",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "course"
                            }
                        },
                        {
                            "requirement_type": "treatment type",
                            "expected_value": "high-dose cytarabine-containing induction chemotherapy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* CML in accelerated phase or myeloid blast crisis that has progressed after treatment with imatinib and a second generation tyrosine kinase inhibitor (e.g., dasatinib or nilotinib)",
            "criterions": [
                {
                    "exact_snippets": "CML in accelerated phase or myeloid blast crisis",
                    "criterion": "CML phase",
                    "requirements": [
                        {
                            "requirement_type": "phase",
                            "expected_value": [
                                "accelerated phase",
                                "myeloid blast crisis"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "has progressed after treatment with imatinib",
                    "criterion": "progression after imatinib treatment",
                    "requirements": [
                        {
                            "requirement_type": "progression",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "has progressed after treatment with ... a second generation tyrosine kinase inhibitor (e.g., dasatinib or nilotinib)",
                    "criterion": "progression after second generation tyrosine kinase inhibitor treatment",
                    "requirements": [
                        {
                            "requirement_type": "progression",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* RAEB with International Prognostic Scoring System (IPSS) score ≥ 2.5, or - CMMOL with IPSS score ≥ 2.5 refractory to or relapsed after a hypomethylating agent (e.g., azacitidine or decitabine) refractory to or relapsed after a hypomethylating agent (e.g., azacitidine or decitabine).",
            "criterions": [
                {
                    "exact_snippets": "RAEB with International Prognostic Scoring System (IPSS) score ≥ 2.5",
                    "criterion": "RAEB IPSS score",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2.5,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "CMMOL with IPSS score ≥ 2.5",
                    "criterion": "CMMOL IPSS score",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2.5,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "CMMOL ... refractory to or relapsed after a hypomethylating agent (e.g., azacitidine or decitabine)",
                    "criterion": "CMMOL response to hypomethylating agent",
                    "requirements": [
                        {
                            "requirement_type": "treatment response",
                            "expected_value": [
                                "refractory",
                                "relapsed"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Greater than 25% of bone marrow blasts must be CD33 positive.",
            "criterions": [
                {
                    "exact_snippets": "Greater than 25% of bone marrow blasts must be CD33 positive.",
                    "criterion": "bone marrow blasts",
                    "requirements": [
                        {
                            "requirement_type": "CD33 positivity",
                            "expected_value": {
                                "operator": ">",
                                "value": 25,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must have a life expectancy of at least 6 weeks and a Karnofsky performance status of ≥ 60%.",
            "criterions": [
                {
                    "exact_snippets": "life expectancy of at least 6 weeks",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 6,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Karnofsky performance status of ≥ 60%",
                    "criterion": "Karnofsky performance status",
                    "requirements": [
                        {
                            "requirement_type": "score",
                            "expected_value": {
                                "operator": ">=",
                                "value": 60,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate renal function as demonstrated by a serum creatinine ≤ 1.5 mg/dl, a creatinine clearance > 60 ml/min, and < 1 gram urinary protein/24 hours.",
            "criterions": [
                {
                    "exact_snippets": "Adequate renal function ... serum creatinine ≤ 1.5 mg/dl",
                    "criterion": "serum creatinine",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "mg/dl"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate renal function ... creatinine clearance > 60 ml/min",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": {
                                "operator": ">",
                                "value": 60,
                                "unit": "ml/min"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate renal function ... < 1 gram urinary protein/24 hours",
                    "criterion": "urinary protein",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<",
                                "value": 1,
                                "unit": "gram/24 hours"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate hepatic function as demonstrated by a bilirubin ≤ 1.5 mg/dl (unless attributable to leukemia or Gilbert's disease) and alkaline phosphatase and AST ≤ 2.5 times the upper limit of normal.",
            "criterions": [
                {
                    "exact_snippets": "bilirubin ≤ 1.5 mg/dl (unless attributable to leukemia or Gilbert's disease)",
                    "criterion": "bilirubin level",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "mg/dl"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "alkaline phosphatase ... ≤ 2.5 times the upper limit of normal",
                    "criterion": "alkaline phosphatase level",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "times the upper limit of normal"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "AST ≤ 2.5 times the upper limit of normal",
                    "criterion": "AST level",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "times the upper limit of normal"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "* Untreated AML, regardless of prognostic features.",
            "criterions": [
                {
                    "exact_snippets": "Untreated AML",
                    "criterion": "AML treatment status",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "untreated"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Treatment with chemotherapy or biologic therapy within 3 weeks of 225Ac- HuM195 administration. Hydroxyurea is permitted but must be discontinued prior to treatment on study. Patients must have recovered from the effects of previous treatment.",
            "criterions": [
                {
                    "exact_snippets": "Treatment with chemotherapy or biologic therapy within 3 weeks of 225Ac- HuM195 administration",
                    "criterion": "recent chemotherapy or biologic therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Hydroxyurea is permitted but must be discontinued prior to treatment on study",
                    "criterion": "hydroxyurea treatment",
                    "requirements": [
                        {
                            "requirement_type": "discontinuation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients must have recovered from the effects of previous treatment",
                    "criterion": "recovery from previous treatment",
                    "requirements": [
                        {
                            "requirement_type": "recovery",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Treatment with radiation therapy within 6 weeks of 225Ac-HuM195 administration. Patients must have recovered from the effects of previous treatment.",
            "criterions": [
                {
                    "exact_snippets": "Treatment with radiation therapy within 6 weeks of 225Ac-HuM195 administration",
                    "criterion": "radiation therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients must have recovered from the effects of previous treatment",
                    "criterion": "recovery from previous treatment",
                    "requirements": [
                        {
                            "requirement_type": "recovery status",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Active serious infections not controlled by antibiotics.",
            "criterions": [
                {
                    "exact_snippets": "Active serious infections not controlled by antibiotics",
                    "criterion": "serious infections",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Pregnant women or women who are breast-feeding.",
            "criterions": [
                {
                    "exact_snippets": "Pregnant women",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "women who are breast-feeding",
                    "criterion": "breast-feeding",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Concurrent active malignancy requiring therapy.",
            "criterions": [
                {
                    "exact_snippets": "Concurrent active malignancy requiring therapy.",
                    "criterion": "concurrent active malignancy",
                    "requirements": [
                        {
                            "requirement_type": "therapy requirement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Clinically significant cardiac disease (NY Heart Association Class III or IV)or pulmonary disease.",
            "criterions": [
                {
                    "exact_snippets": "Clinically significant cardiac disease (NY Heart Association Class III or IV)",
                    "criterion": "cardiac disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "NY Heart Association Class III or IV"
                        }
                    ]
                },
                {
                    "exact_snippets": "Clinically significant ... pulmonary disease",
                    "criterion": "pulmonary disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "clinically significant"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with HLA-compatible donor bone marrow who are immediate candidates for bone marrow transplantation.",
            "criterions": [
                {
                    "exact_snippets": "HLA-compatible donor bone marrow",
                    "criterion": "HLA compatibility",
                    "requirements": [
                        {
                            "requirement_type": "compatibility",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "immediate candidates for bone marrow transplantation",
                    "criterion": "bone marrow transplantation candidacy",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "immediate"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who are candidates for alternative treatments of known effectiveness.",
            "criterions": [
                {
                    "exact_snippets": "candidates for alternative treatments of known effectiveness",
                    "criterion": "alternative treatments",
                    "requirements": [
                        {
                            "requirement_type": "eligibility",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients eligible for protocols of higher priority.",
            "criterions": [
                {
                    "exact_snippets": "Patients eligible for protocols of higher priority.",
                    "criterion": "protocol priority",
                    "requirements": [
                        {
                            "requirement_type": "eligibility",
                            "expected_value": "higher priority"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients previously treated with any monoclonal antibody for any reason.",
            "criterions": [
                {
                    "exact_snippets": "Patients previously treated with any monoclonal antibody",
                    "criterion": "monoclonal antibody treatment",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Active CNS leukemia",
            "criterions": [
                {
                    "exact_snippets": "Active CNS leukemia",
                    "criterion": "CNS leukemia",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Other serious or life-threatening conditions deemed unacceptable by the principal investigator.",
            "criterions": [
                {
                    "exact_snippets": "serious or life-threatening conditions",
                    "criterion": "serious or life-threatening conditions",
                    "requirements": [
                        {
                            "requirement_type": "acceptability",
                            "expected_value": "deemed unacceptable by the principal investigator"
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}