{
    "info": {
        "nct_id": "NCT02420873",
        "official_title": "An Open-label Phase II Study of Lorvotuzumab Mertansine (IMGN901) in CD56 Expressing Hematological Malignancies",
        "inclusion_criteria": "1. Patients with CD56 expressing hematological malignancy, as follows: Cohort 1: CD56 expressing hematological malignancies including but not limited to AML, high-risk myelodysplastic syndrome (MDS), natural-killer leukemia, acute lymphoblastic leukemia, accelerated and blast-phase chronic myelocytic leukemia (CML) who have failed prior therapy or for which no standard therapy exists.Cohort 2: Patients with MF (either primary MF, post-polycythemia MF, or post-essential thrombocythemia MF) and CD56 expression who have been on ruxolitinib or JAK-inhibitor therapy for at least 12 weeks and deemed refractory or sub-optimal responders in the opinion of the treating physician.Cohort 3: Patients with pathological diagnosis of BPDCN with CD56 expression (frontline and relapsed/refractory).\n2. Any level of CD56 expression will be considered sufficient for enrollment on this study.\n3. Prior therapy with hydroxyurea, chemotherapy, biological or targeted therapy (e.g. FLT3 inhibitors, other kinase inhibitors), or hematopoietic growth factors is allowed.\n4. Age >/=18 years\n5. Eastern Cooperative Oncology Group (ECOG) Performance Status </= 2\n6. Adequate organ function: total bilirubin </= 2 times upper limit of normal (x ULN) (</=3 x ULN if considered to be due to leukemic involvement or Gilbert's syndrome); aspartate aminotransferase (AST) or alanine aminotransferase (ALT) </= 2.5 x ULN (</= 5.0 x ULN if considered to be due to leukemic involvement); serum creatinine </= 2 x ULN, amylase and lipase </=2 x ULN .\n7. In the absence of rapidly progressing disease and after discussion with the Principal Investigator (PI), the interval from prior treatment to time of IMGN901 administration will be at least 2 weeks or at least 5 half-lives for cytotoxic/noncytotoxic agents. The half-life be based on published pharmacokinetic literature (abstracts, manuscripts, investigator brochure's, or drug-administration manuals) and will be documented in the protocol eligibility document.\n8. continuation from criteria #7: For prior monoclonal antibody therapy the interval from prior monoclonal antibody treatment to time of IMGN901 administration will be at least 2 weeks. The use of chemotherapeutic or anti-leukemic agents other than hydroxyurea (as defined in the protocol) is not permitted during the study with the exception of intrathecal (IT) therapy for patients with controlled CNS leukemia at the discretion of the PI. Hydroxyurea is allowed prior to the initiation of IMGN901 and during the first 3 cycles, either prior to or concomitantly with IMGN901 administration initially to control Leukocytosis.\n9. Women of childbearing potential must practice contraception. Females of childbearing potential: Recommendation is for 2 effective contraceptive methods during the study. Adequate forms of contraception are double barrier methods (condoms with spermicidal jelly or foam and diaphragm with spermicidal jelly or foam), oral, depo provera, or injectable contraceptives, intrauterine devices, and tubal ligation. Male patients with female partners who are of childbearing potential: Recommendation is for male and partner to use at least 2 effective contraceptive methods, as described above, during the study.\n10. Females must be surgically or biologically sterile or postmenopausal (amenorrheic for at least 12 months) or if of childbearing potential, must have a negative serum or urine pregnancy test within 72 hours before the start of the treatment\n11. Patients must provide written informed consent.\n12. Women of childbearing potential must agree to use an adequate method of contraception during the study and until 3 months after the last treatment. Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 3 months after the last treatment. Adequate methods of contraception include: Total abstinence when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment Male sterilization (at least 6 months prior to screening).\n13. continued from criteria #12: For female patients on the study, the vasectomized male partner should be the sole partner for that patient Combination of any of the two following (a+b or a+c or b+c) Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception Placement of an intrauterine device (IUD) or intrauterine system (IUS) Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository In case of use of oral contraception, women should have been stable on the same pill before taking study treatment. Note: Oral contraceptives are allowed but should be used in conjunction with a barrier method of contraception due to unknown effect of drug-drug interaction\n14. continued from criteria #13 Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "1. Patients with known allergy or hypersensitivity to IMGN901.\n2. Patients who have previously been treated with IMGN901.\n3. Patients with symptomatic central nervous system (CNS) leukemia or patients with poorly controlled central nervous system leukemia.\n4. Peripheral neuropathy >grade 2.\n5. Active or clinically symptomatic chronic pancreatitis or disease affecting pancreas.\n6. Neurologic disease including multiple sclerosis, Eaton-Lambert syndrome, demyelination.\n7. Significant cardiac disease including myocardial infarction or unstable angina within 6 months, uncontrolled hypertension despite medical therapy (defined as blood pressure >160/110 in spite of adequate medical therapy), active and uncontrolled congestive heart failure New York Heart Association (NYHA) class III/IV, stroke within preceding 6 months.\n8. Patients with known Human Immunodeficiency Virus seropositivity will be excluded.\n9. Known to be positive for hepatitis B by surface antigen expression. Known to have active hepatitis C infection (positive by polymerase chain reaction or on antiviral therapy for hepatitis C within the last 6 months). Known to be active CMV infection or herpes zoster infection.\n10. Pregnant or breast feeding (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive B-human chorionic gonadotropin (HCG) laboratory test.\n11. Patients with any concurrent severe and/or uncontrolled medical condition or active uncontrolled systemic infection as determined by the investigator.\n12. Patients who have had any major surgical procedure within 14 days of Day 1.\n13. Patients unwilling or unable to comply with the protocol.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Patients with CD56 expressing hematological malignancy, as follows: Cohort 1: CD56 expressing hematological malignancies including but not limited to AML, high-risk myelodysplastic syndrome (MDS), natural-killer leukemia, acute lymphoblastic leukemia, accelerated and blast-phase chronic myelocytic leukemia (CML) who have failed prior therapy or for which no standard therapy exists.Cohort 2: Patients with MF (either primary MF, post-polycythemia MF, or post-essential thrombocythemia MF) and CD56 expression who have been on ruxolitinib or JAK-inhibitor therapy for at least 12 weeks and deemed refractory or sub-optimal responders in the opinion of the treating physician.Cohort 3: Patients with pathological diagnosis of BPDCN with CD56 expression (frontline and relapsed/refractory).",
            "criterions": [
                {
                    "exact_snippets": "CD56 expressing hematological malignancy",
                    "criterion": "CD56 expression",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "hematological malignancies including but not limited to AML, high-risk myelodysplastic syndrome (MDS), natural-killer leukemia, acute lymphoblastic leukemia, accelerated and blast-phase chronic myelocytic leukemia (CML)",
                    "criterion": "hematological malignancy type",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "AML",
                                "high-risk myelodysplastic syndrome (MDS)",
                                "natural-killer leukemia",
                                "acute lymphoblastic leukemia",
                                "accelerated and blast-phase chronic myelocytic leukemia (CML)"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "failed prior therapy or for which no standard therapy exists",
                    "criterion": "prior therapy status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "failed or no standard therapy"
                        }
                    ]
                },
                {
                    "exact_snippets": "MF (either primary MF, post-polycythemia MF, or post-essential thrombocythemia MF)",
                    "criterion": "myelofibrosis type",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "primary MF",
                                "post-polycythemia MF",
                                "post-essential thrombocythemia MF"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "CD56 expression",
                    "criterion": "CD56 expression",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "been on ruxolitinib or JAK-inhibitor therapy for at least 12 weeks",
                    "criterion": "ruxolitinib or JAK-inhibitor therapy duration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "deemed refractory or sub-optimal responders in the opinion of the treating physician",
                    "criterion": "response to therapy",
                    "requirements": [
                        {
                            "requirement_type": "response",
                            "expected_value": "refractory or sub-optimal"
                        }
                    ]
                },
                {
                    "exact_snippets": "pathological diagnosis of BPDCN with CD56 expression",
                    "criterion": "BPDCN diagnosis",
                    "requirements": [
                        {
                            "requirement_type": "diagnosis",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "CD56 expression",
                    "criterion": "CD56 expression",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Any level of CD56 expression will be considered sufficient for enrollment on this study.",
            "criterions": [
                {
                    "exact_snippets": "Any level of CD56 expression",
                    "criterion": "CD56 expression",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": "any"
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Prior therapy with hydroxyurea, chemotherapy, biological or targeted therapy (e.g. FLT3 inhibitors, other kinase inhibitors), or hematopoietic growth factors is allowed.",
            "criterions": [
                {
                    "exact_snippets": "Prior therapy with hydroxyurea ... is allowed.",
                    "criterion": "prior therapy with hydroxyurea",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior therapy with ... chemotherapy ... is allowed.",
                    "criterion": "prior therapy with chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior therapy with ... biological ... therapy ... is allowed.",
                    "criterion": "prior therapy with biological therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior therapy with ... targeted therapy (e.g. FLT3 inhibitors, other kinase inhibitors) ... is allowed.",
                    "criterion": "prior therapy with targeted therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior therapy with ... hematopoietic growth factors is allowed.",
                    "criterion": "prior therapy with hematopoietic growth factors",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Age >/=18 years",
            "criterions": [
                {
                    "exact_snippets": "Age >/=18 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 18,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Eastern Cooperative Oncology Group (ECOG) Performance Status </= 2",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) Performance Status </= 2",
                    "criterion": "ECOG Performance Status",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Adequate organ function: total bilirubin </= 2 times upper limit of normal (x ULN) (</=3 x ULN if considered to be due to leukemic involvement or Gilbert's syndrome); aspartate aminotransferase (AST) or alanine aminotransferase (ALT) </= 2.5 x ULN (</= 5.0 x ULN if considered to be due to leukemic involvement); serum creatinine </= 2 x ULN, amylase and lipase </=2 x ULN .",
            "criterions": [
                {
                    "exact_snippets": "total bilirubin </= 2 times upper limit of normal (x ULN) (</=3 x ULN if considered to be due to leukemic involvement or Gilbert's syndrome)",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "x ULN"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 3,
                                        "unit": "x ULN"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "aspartate aminotransferase (AST) or alanine aminotransferase (ALT) </= 2.5 x ULN (</= 5.0 x ULN if considered to be due to leukemic involvement)",
                    "criterion": "aspartate aminotransferase (AST) or alanine aminotransferase (ALT)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 2.5,
                                        "unit": "x ULN"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 5.0,
                                        "unit": "x ULN"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "serum creatinine </= 2 x ULN",
                    "criterion": "serum creatinine",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "x ULN"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "amylase and lipase </=2 x ULN",
                    "criterion": "amylase and lipase",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "x ULN"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. In the absence of rapidly progressing disease and after discussion with the Principal Investigator (PI), the interval from prior treatment to time of IMGN901 administration will be at least 2 weeks or at least 5 half-lives for cytotoxic/noncytotoxic agents. The half-life be based on published pharmacokinetic literature (abstracts, manuscripts, investigator brochure's, or drug-administration manuals) and will be documented in the protocol eligibility document.",
            "criterions": [
                {
                    "exact_snippets": "absence of rapidly progressing disease",
                    "criterion": "rapidly progressing disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "interval from prior treatment to time of IMGN901 administration will be at least 2 weeks",
                    "criterion": "interval from prior treatment to IMGN901 administration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "interval from prior treatment to time of IMGN901 administration will be ... at least 5 half-lives for cytotoxic/noncytotoxic agents",
                    "criterion": "interval from prior treatment to IMGN901 administration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 5,
                                "unit": "half-lives"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. continuation from criteria #7: For prior monoclonal antibody therapy the interval from prior monoclonal antibody treatment to time of IMGN901 administration will be at least 2 weeks. The use of chemotherapeutic or anti-leukemic agents other than hydroxyurea (as defined in the protocol) is not permitted during the study with the exception of intrathecal (IT) therapy for patients with controlled CNS leukemia at the discretion of the PI. Hydroxyurea is allowed prior to the initiation of IMGN901 and during the first 3 cycles, either prior to or concomitantly with IMGN901 administration initially to control Leukocytosis.",
            "criterions": [
                {
                    "exact_snippets": "prior monoclonal antibody therapy ... interval ... at least 2 weeks",
                    "criterion": "interval from prior monoclonal antibody treatment to IMGN901 administration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "use of chemotherapeutic or anti-leukemic agents other than hydroxyurea ... is not permitted",
                    "criterion": "use of chemotherapeutic or anti-leukemic agents",
                    "requirements": [
                        {
                            "requirement_type": "permitted",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "intrathecal (IT) therapy for patients with controlled CNS leukemia ... at the discretion of the PI",
                    "criterion": "intrathecal (IT) therapy for patients with controlled CNS leukemia",
                    "requirements": [
                        {
                            "requirement_type": "permitted",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Hydroxyurea is allowed prior to the initiation of IMGN901 and during the first 3 cycles",
                    "criterion": "use of Hydroxyurea",
                    "requirements": [
                        {
                            "requirement_type": "permitted",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Hydroxyurea ... initially to control Leukocytosis",
                    "criterion": "use of Hydroxyurea to control Leukocytosis",
                    "requirements": [
                        {
                            "requirement_type": "purpose",
                            "expected_value": "control Leukocytosis"
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Women of childbearing potential must practice contraception. Females of childbearing potential: Recommendation is for 2 effective contraceptive methods during the study. Adequate forms of contraception are double barrier methods (condoms with spermicidal jelly or foam and diaphragm with spermicidal jelly or foam), oral, depo provera, or injectable contraceptives, intrauterine devices, and tubal ligation. Male patients with female partners who are of childbearing potential: Recommendation is for male and partner to use at least 2 effective contraceptive methods, as described above, during the study.",
            "criterions": [
                {
                    "exact_snippets": "Women of childbearing potential must practice contraception.",
                    "criterion": "contraception for women of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "practice",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Females of childbearing potential: Recommendation is for 2 effective contraceptive methods during the study.",
                    "criterion": "contraceptive methods for females of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "methods"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate forms of contraception are double barrier methods (condoms with spermicidal jelly or foam and diaphragm with spermicidal jelly or foam), oral, depo provera, or injectable contraceptives, intrauterine devices, and tubal ligation.",
                    "criterion": "adequate forms of contraception",
                    "requirements": [
                        {
                            "requirement_type": "types",
                            "expected_value": [
                                "double barrier methods",
                                "oral contraceptives",
                                "depo provera",
                                "injectable contraceptives",
                                "intrauterine devices",
                                "tubal ligation"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Male patients with female partners who are of childbearing potential: Recommendation is for male and partner to use at least 2 effective contraceptive methods, as described above, during the study.",
                    "criterion": "contraceptive methods for male patients with female partners of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "methods"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Females must be surgically or biologically sterile or postmenopausal (amenorrheic for at least 12 months) or if of childbearing potential, must have a negative serum or urine pregnancy test within 72 hours before the start of the treatment",
            "criterions": [
                {
                    "exact_snippets": "Females must be surgically or biologically sterile",
                    "criterion": "sterility",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "postmenopausal (amenorrheic for at least 12 months)",
                    "criterion": "postmenopausal status",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "if of childbearing potential, must have a negative serum or urine pregnancy test within 72 hours before the start of the treatment",
                    "criterion": "pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        },
                        {
                            "requirement_type": "timing",
                            "expected_value": "within 72 hours before the start of the treatment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Patients must provide written informed consent.",
            "criterions": [
                {
                    "exact_snippets": "Patients must provide written informed consent.",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "provision",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. Women of childbearing potential must agree to use an adequate method of contraception during the study and until 3 months after the last treatment. Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 3 months after the last treatment. Adequate methods of contraception include: Total abstinence when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment Male sterilization (at least 6 months prior to screening).",
            "criterions": [
                {
                    "exact_snippets": "Women of childbearing potential must agree to use an adequate method of contraception during the study and until 3 months after the last treatment.",
                    "criterion": "contraception use for women of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 3 months after the last treatment.",
                    "criterion": "contraception use for males",
                    "requirements": [
                        {
                            "requirement_type": "sterility",
                            "expected_value": [
                                "surgically sterile",
                                "biologically sterile"
                            ]
                        },
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate methods of contraception include: Total abstinence when this is in line with the preferred and usual lifestyle of the patient.",
                    "criterion": "adequate methods of contraception",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": "total abstinence"
                        }
                    ]
                },
                {
                    "exact_snippets": "Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.",
                    "criterion": "unacceptable methods of contraception",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": [
                                "periodic abstinence",
                                "withdrawal"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment.",
                    "criterion": "female sterilization",
                    "requirements": [
                        {
                            "requirement_type": "procedure",
                            "expected_value": [
                                "surgical bilateral oophorectomy",
                                "hysterectomy",
                                "tubal ligation"
                            ]
                        },
                        {
                            "requirement_type": "timing",
                            "expected_value": {
                                "operator": ">=",
                                "value": 6,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment",
                    "criterion": "reproductive status confirmation after oophorectomy",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": "follow up hormone level assessment"
                        }
                    ]
                },
                {
                    "exact_snippets": "Male sterilization (at least 6 months prior to screening).",
                    "criterion": "male sterilization",
                    "requirements": [
                        {
                            "requirement_type": "procedure",
                            "expected_value": "sterilization"
                        },
                        {
                            "requirement_type": "timing",
                            "expected_value": {
                                "operator": ">=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. continued from criteria #12: For female patients on the study, the vasectomized male partner should be the sole partner for that patient Combination of any of the two following (a+b or a+c or b+c) Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception Placement of an intrauterine device (IUD) or intrauterine system (IUS) Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository In case of use of oral contraception, women should have been stable on the same pill before taking study treatment. Note: Oral contraceptives are allowed but should be used in conjunction with a barrier method of contraception due to unknown effect of drug-drug interaction",
            "criterions": [
                {
                    "exact_snippets": "female patients",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "expected_value",
                            "expected_value": "female"
                        }
                    ]
                },
                {
                    "exact_snippets": "vasectomized male partner should be the sole partner",
                    "criterion": "partner status",
                    "requirements": [
                        {
                            "requirement_type": "vasectomy",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "exclusivity",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Combination of any of the two following (a+b or a+c or b+c)",
                    "criterion": "contraception method combination",
                    "requirements": [
                        {
                            "requirement_type": "combination",
                            "expected_value": [
                                "a+b",
                                "a+c",
                                "b+c"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Use of oral, injected or implanted hormonal methods of contraception",
                    "criterion": "hormonal contraception method",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": [
                                "oral",
                                "injected",
                                "implanted"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "other forms of hormonal contraception that have comparable efficacy (failure rate <1%)",
                    "criterion": "hormonal contraception efficacy",
                    "requirements": [
                        {
                            "requirement_type": "failure rate",
                            "expected_value": {
                                "operator": "<",
                                "value": 1,
                                "unit": "%"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Placement of an intrauterine device (IUD) or intrauterine system (IUS)",
                    "criterion": "intrauterine device/system",
                    "requirements": [
                        {
                            "requirement_type": "placement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository",
                    "criterion": "barrier contraception method",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": [
                                "Condom",
                                "Occlusive cap"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "In case of use of oral contraception, women should have been stable on the same pill before taking study treatment",
                    "criterion": "oral contraception stability",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Oral contraceptives are allowed but should be used in conjunction with a barrier method of contraception",
                    "criterion": "oral contraceptives with barrier method",
                    "requirements": [
                        {
                            "requirement_type": "conjunction",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "14. continued from criteria #13 Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.",
            "criterions": [
                {
                    "exact_snippets": "12 months of natural (spontaneous) amenorrhea",
                    "criterion": "amenorrhea duration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "age appropriate, history of vasomotor symptoms",
                    "criterion": "clinical profile",
                    "requirements": [
                        {
                            "requirement_type": "appropriateness",
                            "expected_value": [
                                "age appropriate",
                                "history of vasomotor symptoms"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "surgical bilateral oophorectomy (with or without hysterectomy)",
                    "criterion": "surgical history",
                    "requirements": [
                        {
                            "requirement_type": "procedure",
                            "expected_value": "bilateral oophorectomy (with or without hysterectomy)"
                        }
                    ]
                },
                {
                    "exact_snippets": "tubal ligation at least six weeks ago",
                    "criterion": "surgical history",
                    "requirements": [
                        {
                            "requirement_type": "procedure",
                            "expected_value": "tubal ligation"
                        },
                        {
                            "requirement_type": "time since procedure",
                            "expected_value": {
                                "operator": ">=",
                                "value": 6,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment",
                    "criterion": "reproductive status confirmation",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": "follow up hormone level assessment"
                        }
                    ]
                }
            ]
        },
        {
            "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. Patients with known allergy or hypersensitivity to IMGN901.",
            "criterions": [
                {
                    "exact_snippets": "known allergy or hypersensitivity to IMGN901",
                    "criterion": "allergy or hypersensitivity to IMGN901",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Patients who have previously been treated with IMGN901.",
            "criterions": [
                {
                    "exact_snippets": "Patients who have previously been treated with IMGN901",
                    "criterion": "previous treatment with IMGN901",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Patients with symptomatic central nervous system (CNS) leukemia or patients with poorly controlled central nervous system leukemia.",
            "criterions": [
                {
                    "exact_snippets": "symptomatic central nervous system (CNS) leukemia",
                    "criterion": "central nervous system leukemia",
                    "requirements": [
                        {
                            "requirement_type": "symptoms",
                            "expected_value": "symptomatic"
                        }
                    ]
                },
                {
                    "exact_snippets": "poorly controlled central nervous system leukemia",
                    "criterion": "central nervous system leukemia",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "poorly controlled"
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Peripheral neuropathy >grade 2.",
            "criterions": [
                {
                    "exact_snippets": "Peripheral neuropathy >grade 2",
                    "criterion": "peripheral neuropathy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">",
                                "value": 2,
                                "unit": "grade"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Active or clinically symptomatic chronic pancreatitis or disease affecting pancreas.",
            "criterions": [
                {
                    "exact_snippets": "Active or clinically symptomatic chronic pancreatitis",
                    "criterion": "chronic pancreatitis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "disease affecting pancreas",
                    "criterion": "disease affecting pancreas",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Neurologic disease including multiple sclerosis, Eaton-Lambert syndrome, demyelination.",
            "criterions": [
                {
                    "exact_snippets": "Neurologic disease including multiple sclerosis",
                    "criterion": "multiple sclerosis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Neurologic disease including ... Eaton-Lambert syndrome",
                    "criterion": "Eaton-Lambert syndrome",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Neurologic disease including ... demyelination",
                    "criterion": "demyelination",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Significant cardiac disease including myocardial infarction or unstable angina within 6 months, uncontrolled hypertension despite medical therapy (defined as blood pressure >160/110 in spite of adequate medical therapy), active and uncontrolled congestive heart failure New York Heart Association (NYHA) class III/IV, stroke within preceding 6 months.",
            "criterions": [
                {
                    "exact_snippets": "Significant cardiac disease including myocardial infarction or unstable angina within 6 months",
                    "criterion": "myocardial infarction or unstable angina",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 6,
                                        "unit": "months"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled hypertension despite medical therapy (defined as blood pressure >160/110 in spite of adequate medical therapy)",
                    "criterion": "uncontrolled hypertension",
                    "requirements": [
                        {
                            "requirement_type": "blood pressure",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">",
                                        "value": 160,
                                        "unit": "mmHg"
                                    },
                                    {
                                        "operator": ">",
                                        "value": 110,
                                        "unit": "mmHg"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "active and uncontrolled congestive heart failure New York Heart Association (NYHA) class III/IV",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "NYHA class",
                            "expected_value": [
                                "III",
                                "IV"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "stroke within preceding 6 months",
                    "criterion": "stroke",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 6,
                                        "unit": "months"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Patients with known Human Immunodeficiency Virus seropositivity will be excluded.",
            "criterions": [
                {
                    "exact_snippets": "known Human Immunodeficiency Virus seropositivity",
                    "criterion": "Human Immunodeficiency Virus seropositivity",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Known to be positive for hepatitis B by surface antigen expression. Known to have active hepatitis C infection (positive by polymerase chain reaction or on antiviral therapy for hepatitis C within the last 6 months). Known to be active CMV infection or herpes zoster infection.",
            "criterions": [
                {
                    "exact_snippets": "Known to be positive for hepatitis B by surface antigen expression.",
                    "criterion": "hepatitis B",
                    "requirements": [
                        {
                            "requirement_type": "surface antigen expression",
                            "expected_value": "positive"
                        }
                    ]
                },
                {
                    "exact_snippets": "Known to have active hepatitis C infection (positive by polymerase chain reaction or on antiviral therapy for hepatitis C within the last 6 months).",
                    "criterion": "hepatitis C infection",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        }
                    ]
                },
                {
                    "exact_snippets": "Known to be active CMV infection",
                    "criterion": "CMV infection",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        }
                    ]
                },
                {
                    "exact_snippets": "herpes zoster infection",
                    "criterion": "herpes zoster infection",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Pregnant or breast feeding (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive B-human chorionic gonadotropin (HCG) laboratory test.",
            "criterions": [
                {
                    "exact_snippets": "Pregnant ... confirmed by a positive B-human chorionic gonadotropin (HCG) laboratory test.",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": "positive B-human chorionic gonadotropin (HCG) laboratory test"
                        }
                    ]
                },
                {
                    "exact_snippets": "breast feeding (lactating) women",
                    "criterion": "breastfeeding",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Patients with any concurrent severe and/or uncontrolled medical condition or active uncontrolled systemic infection as determined by the investigator.",
            "criterions": [
                {
                    "exact_snippets": "any concurrent severe and/or uncontrolled medical condition",
                    "criterion": "medical condition",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        },
                        {
                            "requirement_type": "control",
                            "expected_value": "uncontrolled"
                        }
                    ]
                },
                {
                    "exact_snippets": "active uncontrolled systemic infection",
                    "criterion": "systemic infection",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        },
                        {
                            "requirement_type": "control",
                            "expected_value": "uncontrolled"
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. Patients who have had any major surgical procedure within 14 days of Day 1.",
            "criterions": [
                {
                    "exact_snippets": "Patients who have had any major surgical procedure within 14 days of Day 1.",
                    "criterion": "major surgical procedure",
                    "requirements": [
                        {
                            "requirement_type": "time since procedure",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 14,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. Patients unwilling or unable to comply with the protocol.",
            "criterions": [
                {
                    "exact_snippets": "Patients unwilling ... to comply with the protocol.",
                    "criterion": "willingness to comply with the protocol",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients ... unable to comply with the protocol.",
                    "criterion": "ability to comply with the protocol",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}