{
    "info": {
        "nct_id": "NCT05887882",
        "official_title": "A Phase I Study of Intra-Tumoral Injections of Ex Vivo Expanded Natural Killer Cells in Children and Young Adults With Recurrent or Progressive Supratentorial Malignant Brain Tumors",
        "inclusion_criteria": "1. Participants must have a histologically-confirmed recurrent or progressive, non-metastatic supratentorial World Health Organization (WHO) Grade III/IV malignant brain tumor. Including, but not limited to: anaplastic ependymoma, embryonal tumor, primitive neuroectodermal tumor, atypical teratoid rhabdoid tumor (ATRT), anaplastic astrocytoma, anaplastic oligoastrocytoma, anaplastic oligodendroglioma, anaplastic pleomorphic xanthoastrocytoma, glioblastoma multiforme, gliosarcoma, or malignant glioma (NOS), WHO Grade II ependymoma.\n2. Participants should be candidates for resection of the recurrent tumor and be deemed candidate for placement of an Ommaya reservoir placed intra-cavitary/intra-tumoral; measurable residual tumor after surgery is not required for study entry. Pre-operative imaging need to estimate that the resection cavity will be at least 2 cm x 2 cm in two dimensions for patients to be eligible.\n3. Given the lack of a standard of care treatment for children with recurrent or progressive grade III/IV malignant brain tumors, participants must have completed first-line treatment with radiation and/or chemotherapy prior to participating in this trial.\n4. All participants must be >= 1 year of age and < 39 years of age at the time of entry into the study. The first 3 participants must be >= 8 years of age and < 39 years of age at the time of entry into the study.\n5. Performance Score: Karnofsky >= 50 for participants > 16 years of age and Lansky >= 50 for participants <=16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.\n6. Must have recovered from the acute toxic effects of prior therapy (i.e., NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5, grade 1 or less)\n\n   * An interval of at least 12 weeks must have elapsed since the completion of radiation therapy.\n   * At least 6 weeks since the completion of any cytotoxic chemotherapy regimen.\n   * At least 12 weeks since the completion of any immunotherapies or cell therapies.\n   * For targeted agents only, participants should have recovered from any toxicity of the agent and have a minimum of 2 weeks since the last dose.\n   * For participants who have received prior bevacizumab, at least 6 weeks is required.\n7. Organ Function Requirements:\n\n   1. Adequate Bone Marrow Function Defined as:\n\n      * Peripheral absolute neutrophil count (ANC) >750/mm^3.\n      * Platelet count >75,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).\n   2. Adequate Renal Function Defined as:\n\n      * A serum creatinine <= 1.5 x upper limit normal (ULN) based on age/gender.\n   3. Adequate Liver Function Defined as:\n\n      * Total bilirubin <= 1.5 x upper limit of normal (ULN) for age; in presence of Gilbert's syndrome, total bilirubin <= 3 x ULN or direct bilirubin <= 1.5 x ULN.\n      * Alanine aminotransferase (ALT) <= 3 x ULN.\n      * Aspartate aminotransferase (AST) <= 3 x ULN.\n   4. Adequate Neurologic Function Defined as:\n\n      * Participants with seizure disorder may be enrolled if seizures are well-controlled. Participants on non-enzyme inducing anticonvulsants may be excluded pending interaction(s) with study drug.\n      * Signs and symptoms of neurologic deficit must be stable for >= 1 week prior to enrollment.\n8. The effects of Transforming growth factor beta resistant (TGFβi) natural killer (NK) cells on the developing human fetus are unknown. For this reason and because TGFβi NK cells as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 6 months after completion of TGFβi NK cells administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.\n9. A legal parent/guardian or patient must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.\n10. Participants who are receiving dexamethasone must be on a stable or decreasing dose for 1-week prior to registration.\nHealthy volunteers allowed\nMust have minimum age of 1 Year\nMust have maximum age of 38 Years",
        "exclusion_criteria": "1. Participants with evidence of disseminated disease, including multi-focal disease, diffuse leptomeningeal disease, Cerebral spinal fluid (CSF) dissemination or extra-neural disease.\n2. Tumor involvement that would require ventricular, brainstem or posterior fossa injection or access through a ventricle or risk of ventricular penetration in order to deliver the TGFβi NK cells.\n3. Participants undergoing needle or open biopsy.\n4. Participants who are receiving any other investigational agents.\n5. Women of childbearing potential must not be pregnant or breast-feeding.\n6. Evidence of active uncontrolled infection or unstable or severe intercurrent medical conditions.\n7. Any medical condition that precludes surgery.\n8. Prothrombin time/international normalized ratio (PT/INR) or partial thromboplastin time (PTT) > 1.5 x ULN.\n9. Participants with a known disorder that affects their immune system, such as human immunodeficiency virus (HIV), or an auto- immune disorder requiring systemic cytotoxic or immunosuppressive therapy are not eligible.\n10. Evidence of bleeding diathesis or use of anticoagulant medication or any medication which may increase the risk of bleeding. If the medication can be discontinued >1 week prior to NK cell infusion then the subject may be eligible following consultation with the Study Chairs.\n11. Participants with significant systemic or major illnesses including but not limited to: congestive heart failure, ischemic heart disease, kidney disease or renal failure, organ transplantation, or significant psychiatric disorder.\n12. History or current diagnosis of any medical or psychological condition that in the Investigator's opinion, might interfere with the participants ability to participate or inability to obtain informed consent because of psychiatric or complicating medical problems.\n\nImportant note: The eligibility criteria listed above are interpreted literally and cannot be waived.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Participants must have a histologically-confirmed recurrent or progressive, non-metastatic supratentorial World Health Organization (WHO) Grade III/IV malignant brain tumor. Including, but not limited to: anaplastic ependymoma, embryonal tumor, primitive neuroectodermal tumor, atypical teratoid rhabdoid tumor (ATRT), anaplastic astrocytoma, anaplastic oligoastrocytoma, anaplastic oligodendroglioma, anaplastic pleomorphic xanthoastrocytoma, glioblastoma multiforme, gliosarcoma, or malignant glioma (NOS), WHO Grade II ependymoma.",
            "criterions": [
                {
                    "exact_snippets": "histologically-confirmed recurrent or progressive, non-metastatic supratentorial World Health Organization (WHO) Grade III/IV malignant brain tumor",
                    "criterion": "malignant brain tumor",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": "histologically-confirmed"
                        },
                        {
                            "requirement_type": "recurrence",
                            "expected_value": "recurrent or progressive"
                        },
                        {
                            "requirement_type": "metastasis",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "location",
                            "expected_value": "supratentorial"
                        },
                        {
                            "requirement_type": "grade",
                            "expected_value": [
                                "WHO Grade III",
                                "WHO Grade IV"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "anaplastic ependymoma, embryonal tumor, primitive neuroectodermal tumor, atypical teratoid rhabdoid tumor (ATRT), anaplastic astrocytoma, anaplastic oligoastrocytoma, anaplastic oligodendroglioma, anaplastic pleomorphic xanthoastrocytoma, glioblastoma multiforme, gliosarcoma, or malignant glioma (NOS), WHO Grade II ependymoma",
                    "criterion": "specific tumor types",
                    "requirements": [
                        {
                            "requirement_type": "types",
                            "expected_value": [
                                "anaplastic ependymoma",
                                "embryonal tumor",
                                "primitive neuroectodermal tumor",
                                "atypical teratoid rhabdoid tumor (ATRT)",
                                "anaplastic astrocytoma",
                                "anaplastic oligoastrocytoma",
                                "anaplastic oligodendroglioma",
                                "anaplastic pleomorphic xanthoastrocytoma",
                                "glioblastoma multiforme",
                                "gliosarcoma",
                                "malignant glioma (NOS)",
                                "WHO Grade II ependymoma"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Participants should be candidates for resection of the recurrent tumor and be deemed candidate for placement of an Ommaya reservoir placed intra-cavitary/intra-tumoral; measurable residual tumor after surgery is not required for study entry. Pre-operative imaging need to estimate that the resection cavity will be at least 2 cm x 2 cm in two dimensions for patients to be eligible.",
            "criterions": [
                {
                    "exact_snippets": "candidates for resection of the recurrent tumor",
                    "criterion": "recurrent tumor resection candidacy",
                    "requirements": [
                        {
                            "requirement_type": "candidacy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "candidate for placement of an Ommaya reservoir placed intra-cavitary/intra-tumoral",
                    "criterion": "Ommaya reservoir placement candidacy",
                    "requirements": [
                        {
                            "requirement_type": "candidacy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "measurable residual tumor after surgery is not required for study entry",
                    "criterion": "measurable residual tumor",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Pre-operative imaging need to estimate that the resection cavity will be at least 2 cm x 2 cm in two dimensions",
                    "criterion": "resection cavity size",
                    "requirements": [
                        {
                            "requirement_type": "size",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 2,
                                        "unit": "cm"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Given the lack of a standard of care treatment for children with recurrent or progressive grade III/IV malignant brain tumors, participants must have completed first-line treatment with radiation and/or chemotherapy prior to participating in this trial.",
            "criterions": [
                {
                    "exact_snippets": "children with recurrent or progressive grade III/IV malignant brain tumors",
                    "criterion": "malignant brain tumors",
                    "requirements": [
                        {
                            "requirement_type": "grade",
                            "expected_value": [
                                "III",
                                "IV"
                            ]
                        },
                        {
                            "requirement_type": "recurrence",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "progression",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "participants must have completed first-line treatment with radiation and/or chemotherapy",
                    "criterion": "first-line treatment",
                    "requirements": [
                        {
                            "requirement_type": "completion",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "treatment type",
                            "expected_value": [
                                "radiation",
                                "chemotherapy"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. All participants must be >= 1 year of age and < 39 years of age at the time of entry into the study. The first 3 participants must be >= 8 years of age and < 39 years of age at the time of entry into the study.",
            "criterions": [
                {
                    "exact_snippets": "All participants must be >= 1 year of age and < 39 years of age",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 1,
                                        "unit": "year"
                                    },
                                    {
                                        "operator": "<",
                                        "value": 39,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "The first 3 participants must be >= 8 years of age and < 39 years of age",
                    "criterion": "age for first 3 participants",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 8,
                                        "unit": "years"
                                    },
                                    {
                                        "operator": "<",
                                        "value": 39,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Performance Score: Karnofsky >= 50 for participants > 16 years of age and Lansky >= 50 for participants <=16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.",
            "criterions": [
                {
                    "exact_snippets": "Performance Score: Karnofsky >= 50 for participants > 16 years of age",
                    "criterion": "Karnofsky Performance Score",
                    "requirements": [
                        {
                            "requirement_type": "score",
                            "expected_value": {
                                "operator": ">=",
                                "value": 50,
                                "unit": "N/A"
                            }
                        },
                        {
                            "requirement_type": "age",
                            "expected_value": {
                                "operator": ">",
                                "value": 16,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Performance Score: ... Lansky >= 50 for participants <=16 years of age",
                    "criterion": "Lansky Performance Score",
                    "requirements": [
                        {
                            "requirement_type": "score",
                            "expected_value": {
                                "operator": ">=",
                                "value": 50,
                                "unit": "N/A"
                            }
                        },
                        {
                            "requirement_type": "age",
                            "expected_value": {
                                "operator": "<=",
                                "value": 16,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory",
                    "criterion": "ambulatory status",
                    "requirements": [
                        {
                            "requirement_type": "condition",
                            "expected_value": "considered ambulatory if up in a wheelchair despite paralysis"
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Must have recovered from the acute toxic effects of prior therapy (i.e., NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5, grade 1 or less)",
            "criterions": [
                {
                    "exact_snippets": "recovered from the acute toxic effects of prior therapy",
                    "criterion": "recovery from acute toxic effects of prior therapy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "grade"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* An interval of at least 12 weeks must have elapsed since the completion of radiation therapy.",
            "criterions": [
                {
                    "exact_snippets": "An interval of at least 12 weeks must have elapsed since the completion of radiation therapy.",
                    "criterion": "interval since completion of radiation therapy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* At least 6 weeks since the completion of any cytotoxic chemotherapy regimen.",
            "criterions": [
                {
                    "exact_snippets": "At least 6 weeks since the completion of any cytotoxic chemotherapy regimen.",
                    "criterion": "time since completion of cytotoxic chemotherapy regimen",
                    "requirements": [
                        {
                            "requirement_type": "time since completion",
                            "expected_value": {
                                "operator": ">=",
                                "value": 6,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* At least 12 weeks since the completion of any immunotherapies or cell therapies.",
            "criterions": [
                {
                    "exact_snippets": "At least 12 weeks since the completion of any immunotherapies",
                    "criterion": "immunotherapy completion",
                    "requirements": [
                        {
                            "requirement_type": "time since completion",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "At least 12 weeks since the completion of ... cell therapies",
                    "criterion": "cell therapy completion",
                    "requirements": [
                        {
                            "requirement_type": "time since completion",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* For targeted agents only, participants should have recovered from any toxicity of the agent and have a minimum of 2 weeks since the last dose.",
            "criterions": [
                {
                    "exact_snippets": "participants should have recovered from any toxicity of the agent",
                    "criterion": "recovery from toxicity",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "recovered"
                        }
                    ]
                },
                {
                    "exact_snippets": "have a minimum of 2 weeks since the last dose",
                    "criterion": "time since last dose",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* For participants who have received prior bevacizumab, at least 6 weeks is required.",
            "criterions": [
                {
                    "exact_snippets": "participants who have received prior bevacizumab",
                    "criterion": "prior bevacizumab treatment",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "at least 6 weeks is required",
                    "criterion": "time since prior bevacizumab treatment",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 6,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Organ Function Requirements:",
            "criterions": [
                {
                    "exact_snippets": "Organ Function Requirements",
                    "criterion": "organ function",
                    "requirements": [
                        {
                            "requirement_type": "N/A",
                            "expected_value": "requirements"
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Adequate Bone Marrow Function Defined as:",
            "criterions": [
                {
                    "exact_snippets": "Adequate Bone Marrow Function",
                    "criterion": "bone marrow function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Peripheral absolute neutrophil count (ANC) >750/mm^3.",
            "criterions": [
                {
                    "exact_snippets": "Peripheral absolute neutrophil count (ANC) >750/mm^3",
                    "criterion": "peripheral absolute neutrophil count (ANC)",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">",
                                "value": 750,
                                "unit": "mm^3"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Platelet count >75,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).",
            "criterions": [
                {
                    "exact_snippets": "Platelet count >75,000/mm^3",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">",
                                "value": 75000,
                                "unit": "mm^3"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment",
                    "criterion": "transfusion independence",
                    "requirements": [
                        {
                            "requirement_type": "duration since last transfusion",
                            "expected_value": {
                                "operator": ">=",
                                "value": 7,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Adequate Renal Function Defined as:",
            "criterions": [
                {
                    "exact_snippets": "Adequate Renal Function",
                    "criterion": "renal function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* A serum creatinine <= 1.5 x upper limit normal (ULN) based on age/gender.",
            "criterions": [
                {
                    "exact_snippets": "serum creatinine <= 1.5 x upper limit normal (ULN)",
                    "criterion": "serum creatinine",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Adequate Liver Function Defined as:",
            "criterions": [
                {
                    "exact_snippets": "Adequate Liver Function",
                    "criterion": "liver function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Total bilirubin <= 1.5 x upper limit of normal (ULN) for age; in presence of Gilbert's syndrome, total bilirubin <= 3 x ULN or direct bilirubin <= 1.5 x ULN.",
            "criterions": [
                {
                    "exact_snippets": "Total bilirubin <= 1.5 x upper limit of normal (ULN) for age",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 1.5,
                                        "unit": "x ULN"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "in presence of Gilbert's syndrome, total bilirubin <= 3 x ULN",
                    "criterion": "total bilirubin in presence of Gilbert's syndrome",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 3,
                                        "unit": "x ULN"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "in presence of Gilbert's syndrome, ... direct bilirubin <= 1.5 x ULN",
                    "criterion": "direct bilirubin in presence of Gilbert's syndrome",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 1.5,
                                        "unit": "x ULN"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Alanine aminotransferase (ALT) <= 3 x ULN.",
            "criterions": [
                {
                    "exact_snippets": "Alanine aminotransferase (ALT) <= 3 x ULN.",
                    "criterion": "Alanine aminotransferase (ALT)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Aspartate aminotransferase (AST) <= 3 x ULN.",
            "criterions": [
                {
                    "exact_snippets": "Aspartate aminotransferase (AST) <= 3 x ULN",
                    "criterion": "aspartate aminotransferase (AST)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Adequate Neurologic Function Defined as:",
            "criterions": [
                {
                    "exact_snippets": "Adequate Neurologic Function",
                    "criterion": "neurologic function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participants with seizure disorder may be enrolled if seizures are well-controlled. Participants on non-enzyme inducing anticonvulsants may be excluded pending interaction(s) with study drug.",
            "criterions": [
                {
                    "exact_snippets": "Participants with seizure disorder",
                    "criterion": "seizure disorder",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "seizures are well-controlled",
                    "criterion": "seizure control",
                    "requirements": [
                        {
                            "requirement_type": "control status",
                            "expected_value": "well-controlled"
                        }
                    ]
                },
                {
                    "exact_snippets": "Participants on non-enzyme inducing anticonvulsants",
                    "criterion": "non-enzyme inducing anticonvulsants",
                    "requirements": [
                        {
                            "requirement_type": "use",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "interaction(s) with study drug",
                    "criterion": "interaction with study drug",
                    "requirements": [
                        {
                            "requirement_type": "potential",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Signs and symptoms of neurologic deficit must be stable for >= 1 week prior to enrollment.",
            "criterions": [
                {
                    "exact_snippets": "Signs and symptoms of neurologic deficit must be stable for >= 1 week",
                    "criterion": "neurologic deficit",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "week"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. The effects of Transforming growth factor beta resistant (TGFβi) natural killer (NK) cells on the developing human fetus are unknown. For this reason and because TGFβi NK cells as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 6 months after completion of TGFβi NK cells administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.",
            "criterions": [
                {
                    "exact_snippets": "women of child-bearing potential",
                    "criterion": "women of child-bearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "men must agree to use adequate contraception",
                    "criterion": "men contraception agreement",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "women of child-bearing potential ... must agree to use adequate contraception",
                    "criterion": "women contraception agreement",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "adequate contraception (hormonal or barrier method of birth control; abstinence)",
                    "criterion": "contraception method",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "hormonal",
                                "barrier method of birth control",
                                "abstinence"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "prior to study entry, for the duration of study participation and 6 months after completion of TGFβi NK cells administration",
                    "criterion": "contraception duration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "prior to study entry, for the duration of study participation and 6 months after completion of TGFβi NK cells administration"
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. A legal parent/guardian or patient must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.",
            "criterions": [
                {
                    "exact_snippets": "A legal parent/guardian or patient must be able to understand",
                    "criterion": "understanding of informed consent",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "willing to sign, a written informed consent and assent document",
                    "criterion": "willingness to sign informed consent",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Participants who are receiving dexamethasone must be on a stable or decreasing dose for 1-week prior to registration.",
            "criterions": [
                {
                    "exact_snippets": "Participants who are receiving dexamethasone",
                    "criterion": "dexamethasone treatment",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "must be on a stable or decreasing dose",
                    "criterion": "dexamethasone dose stability",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": [
                                "stable",
                                "decreasing"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "for 1-week prior to registration",
                    "criterion": "dexamethasone dose stability duration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "week"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "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 1 Year",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 1 Year",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "Year"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have maximum age of 38 Years",
            "criterions": [
                {
                    "exact_snippets": "maximum age of 38 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "N/A",
                            "expected_value": {
                                "operator": "<=",
                                "value": 38,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "1. Participants with evidence of disseminated disease, including multi-focal disease, diffuse leptomeningeal disease, Cerebral spinal fluid (CSF) dissemination or extra-neural disease.",
            "criterions": [
                {
                    "exact_snippets": "evidence of disseminated disease",
                    "criterion": "disseminated disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "multi-focal disease",
                    "criterion": "multi-focal disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "diffuse leptomeningeal disease",
                    "criterion": "diffuse leptomeningeal disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Cerebral spinal fluid (CSF) dissemination",
                    "criterion": "CSF dissemination",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "extra-neural disease",
                    "criterion": "extra-neural disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Tumor involvement that would require ventricular, brainstem or posterior fossa injection or access through a ventricle or risk of ventricular penetration in order to deliver the TGFβi NK cells.",
            "criterions": [
                {
                    "exact_snippets": "Tumor involvement that would require ventricular, brainstem or posterior fossa injection",
                    "criterion": "tumor involvement",
                    "requirements": [
                        {
                            "requirement_type": "location",
                            "expected_value": [
                                "ventricular",
                                "brainstem",
                                "posterior fossa"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "access through a ventricle",
                    "criterion": "access requirement",
                    "requirements": [
                        {
                            "requirement_type": "location",
                            "expected_value": "ventricle"
                        }
                    ]
                },
                {
                    "exact_snippets": "risk of ventricular penetration",
                    "criterion": "risk of ventricular penetration",
                    "requirements": [
                        {
                            "requirement_type": "risk",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Participants undergoing needle or open biopsy.",
            "criterions": [
                {
                    "exact_snippets": "Participants undergoing needle or open biopsy",
                    "criterion": "biopsy",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "needle",
                                "open"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Participants who are receiving any other investigational agents.",
            "criterions": [
                {
                    "exact_snippets": "Participants who are receiving any other investigational agents",
                    "criterion": "receiving investigational agents",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Women of childbearing potential must not be pregnant or breast-feeding.",
            "criterions": [
                {
                    "exact_snippets": "Women of childbearing potential must not be pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Women of childbearing potential must not be ... breast-feeding",
                    "criterion": "breast-feeding",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Evidence of active uncontrolled infection or unstable or severe intercurrent medical conditions.",
            "criterions": [
                {
                    "exact_snippets": "Evidence of active uncontrolled infection",
                    "criterion": "active uncontrolled infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "unstable or severe intercurrent medical conditions",
                    "criterion": "unstable or severe intercurrent medical conditions",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Any medical condition that precludes surgery.",
            "criterions": [
                {
                    "exact_snippets": "Any medical condition that precludes surgery.",
                    "criterion": "medical condition",
                    "requirements": [
                        {
                            "requirement_type": "impact on surgery",
                            "expected_value": "precludes"
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Prothrombin time/international normalized ratio (PT/INR) or partial thromboplastin time (PTT) > 1.5 x ULN.",
            "criterions": [
                {
                    "exact_snippets": "Prothrombin time/international normalized ratio (PT/INR) ... > 1.5 x ULN",
                    "criterion": "Prothrombin time/international normalized ratio (PT/INR)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "partial thromboplastin time (PTT) > 1.5 x ULN",
                    "criterion": "partial thromboplastin time (PTT)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Participants with a known disorder that affects their immune system, such as human immunodeficiency virus (HIV), or an auto- immune disorder requiring systemic cytotoxic or immunosuppressive therapy are not eligible.",
            "criterions": [
                {
                    "exact_snippets": "known disorder that affects their immune system",
                    "criterion": "immune system disorder",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "human immunodeficiency virus (HIV)",
                    "criterion": "HIV",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "auto- immune disorder requiring systemic cytotoxic or immunosuppressive therapy",
                    "criterion": "autoimmune disorder requiring systemic cytotoxic or immunosuppressive therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Evidence of bleeding diathesis or use of anticoagulant medication or any medication which may increase the risk of bleeding. If the medication can be discontinued >1 week prior to NK cell infusion then the subject may be eligible following consultation with the Study Chairs.",
            "criterions": [
                {
                    "exact_snippets": "Evidence of bleeding diathesis",
                    "criterion": "bleeding diathesis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "use of anticoagulant medication",
                    "criterion": "anticoagulant medication",
                    "requirements": [
                        {
                            "requirement_type": "use",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "any medication which may increase the risk of bleeding",
                    "criterion": "medication increasing bleeding risk",
                    "requirements": [
                        {
                            "requirement_type": "use",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Participants with significant systemic or major illnesses including but not limited to: congestive heart failure, ischemic heart disease, kidney disease or renal failure, organ transplantation, or significant psychiatric disorder.",
            "criterions": [
                {
                    "exact_snippets": "significant systemic or major illnesses ... congestive heart failure",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "significant systemic or major illnesses ... ischemic heart disease",
                    "criterion": "ischemic heart disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "significant systemic or major illnesses ... kidney disease or renal failure",
                    "criterion": "kidney disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "significant systemic or major illnesses ... kidney disease or renal failure",
                    "criterion": "renal failure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "significant systemic or major illnesses ... organ transplantation",
                    "criterion": "organ transplantation",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "significant systemic or major illnesses ... significant psychiatric disorder",
                    "criterion": "significant psychiatric disorder",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. History or current diagnosis of any medical or psychological condition that in the Investigator's opinion, might interfere with the participants ability to participate or inability to obtain informed consent because of psychiatric or complicating medical problems.",
            "criterions": [
                {
                    "exact_snippets": "History or current diagnosis of any medical or psychological condition",
                    "criterion": "medical or psychological condition",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "inability to obtain informed consent because of psychiatric or complicating medical problems",
                    "criterion": "ability to obtain informed consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Important note: The eligibility criteria listed above are interpreted literally and cannot be waived.",
            "criterions": [
                {
                    "exact_snippets": "eligibility criteria",
                    "criterion": "eligibility criteria",
                    "requirements": [
                        {
                            "requirement_type": "interpretation",
                            "expected_value": "literal"
                        },
                        {
                            "requirement_type": "waiver",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}