{
    "info": {
        "nct_id": "NCT06284460",
        "official_title": "Phase I/II Study of a Combination of Decitabine and Cedazuridine (ASTX727) and ASTX029, an ERK Inhibitor, for Patients With RAS Pathway Mutant Myelodysplastic Syndromes and Myelodysplastic/Myeloproliferative Neoplasms",
        "inclusion_criteria": "* Age ≥ 18 years as MDS and MDS/MPN are a very rare disease in the pediatric setting.\n* Diagnosis of MDS or MDS/MPN (including CMML, aCML, MDS/MPN-U) according to WHO and:\n\n  * Initial phase 1 cohorts (cohorts A): MDS participants with no response after 4 cycles of azacitidine, decitabine, guadecitabine, CC-486 or ASTX727 or relapse or progression after any number of cycles OR MDS/MPN relapsed/refractory following treatment with hydroxyurea OR at least 4 cycles of azacytidine, decitabine, guadecitabine or ASTX727 or relapse or progression after any number of cycles or who are intolerant of treatment with hydroxiurea.\n  * Phase 2 dose expansion cohort:\n  * Relapsed MDS cohort (Cohort B): no response after 4 cycles of azacitidine, decitabine, guadecitabine or ASTX727 or relapse or progression after any number of cycles.\n  * Relapsed MDS/MPN cohort (Cohort C): relapsed/refractory following treatment with hydroxyurea or at least 4 cycles of azacytidine, decitabine, guadecitabine or ASTX727 or relapse or progression after any number of cycles or who are intolerant of treatment with wih hydroxiurea.\n* Known mutation in genes leading to RAS pathway activation (NRAS, KRAS, BRAF, CBL, NF1, PTPN11).\n* Creatinine clearance ≥30ml/min based on the Cockcroft-Gault Glomerular Filtration Rate estimation.\n* Adequate hepatic function with total bilirubin ≤1.5x ULN, AST or ALT ≤3 xULN.\n* ECOG Performance Status 0-2.\n* Participant (or patient's legally authorized representative) must have signed an informed consent document indicating that the participant understands the purpose of and procedures required for the study and is willing to participate in the study. Non-English speaking participants may be consented.\n* Prior hydroxyurea for control of leukocytosis or use of hematopoietic growth factors (eg, G-CSF, GM-CSF, procrit, aranesp, thrombopoietins) is allowed at any time prior to cycle 1 day 1 of therapy.\n* For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.\n* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.\n* Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. The effects of ASTX029 on the developing human fetus are unknown. For this reason and because 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 and for the duration of study participation. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). This includes all female participants, between the onset of menses (as early as 8 years of age) and 55 years unless the participant presents with an applicable exclusionary factor which may be one of the following:\n\n  * Postmenopausal (no menses in greater than or equal to 12 consecutive months).\n  * History of hysterectomy or bilateral salpingo-oophorectomy.\n  * Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).\n  * History of bilateral tubal ligation or another surgical sterilization procedure.\n* Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. 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.\n* Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of ASTX727 and ASTX029 administration.\n* Ability to understand and the willingness to sign a written informed consent document.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Participants who are currently receiving treatment for a malignancy (not including basal cell carcinoma, nonmelanoma skin cancer, cervical carcinoma in situ, early stage breast cancer or localized prostate cancer treated with hormone therapy). Participants with history of other cancers should be free of disease for at least 2 years prior to the Screening Visit or not requiring active treatment at the time of enrollment.\n* Participants who are receiving any other investigational agents.\n* Participants who have an active, life-threatening, or clinically-significant uncontrolled systemic infection requiring hospitalization.\n* Participants who have a known malabsorption syndrome or other condition that may impair absorption of study medication (e.g., gastrectomy).\n* Pregnant women are excluded from this study because ASTX029 and ASTX727 are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is treated on study. These potential risks may also apply to other agents used in this study.\n* Participants with reproductive potential who are unwilling to following contraception requirements (including condom use for males with sexual partners, and for females: prescription oral contraceptives [birth control pills], contraceptive injections, intrauterine devices [IUD], double-barrier method [spermicidal jelly or foam with condoms or diaphragm], contraceptive patch, or surgical sterilization) throughout the study.\n* Female participants with reproductive potential who do not have a negative urine or blood beta-human chorionic gonadotropin (beta HCG) pregnancy test at screening.\n* Participants receiving any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy within 7 days of therapy initiation.\n* Participants known to be positive for hepatitis B surface antigen expression or with active hepatitis C infection (positive by polymerase chain reaction or on antiviral therapy for hepatitis C within the last 6 months).\n* Participants with history of HIV with CD4+ T-cell (CD4+) counts <350 cell/mcL or with AIDS-defining opportunistic infections in the last 12 months are also excluded. Participants with well controlled HIV (defined as CD4+ counts >350 cells/mcL with undetectable viral load prior to enrollment with no AIDS-defining opportunistic infections in the past 12 months) on therapy with antiretroviral therapies known to be metabolites of cytochrome P450 (CYP3A4) enzymes will also be excluded.\n* Participants with QTc interval >480 msec based on average of triplicate ECG readings at the Screening Visit using the Fridericia formula (QTcF), with the exception of participants with right bundle branch block or left bundle branch block.\n* New York Heart Association (NYHA) Class III or IV congestive heart failure or LVEF <50 by echocardiogram or multigated acquisition (MUGA) scan.\n* History of myocardial infarction within the last 6 months or unstable/uncontrolled angina pectoris or history of severe and/or uncontrolled ventricular arrhythmias.\n* Participants with psychiatric illness/social situations that would limit compliance with study requirements.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Age ≥ 18 years as MDS and MDS/MPN are a very rare disease in the pediatric setting.",
            "criterions": [
                {
                    "exact_snippets": "Age ≥ 18 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Diagnosis of MDS or MDS/MPN (including CMML, aCML, MDS/MPN-U) according to WHO and:",
            "criterions": [
                {
                    "exact_snippets": "Diagnosis of MDS or MDS/MPN (including CMML, aCML, MDS/MPN-U)",
                    "criterion": "diagnosis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "MDS",
                                "MDS/MPN",
                                "CMML",
                                "aCML",
                                "MDS/MPN-U"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "according to WHO",
                    "criterion": "diagnosis criteria",
                    "requirements": [
                        {
                            "requirement_type": "standard",
                            "expected_value": "WHO"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Initial phase 1 cohorts (cohorts A): MDS participants with no response after 4 cycles of azacitidine, decitabine, guadecitabine, CC-486 or ASTX727 or relapse or progression after any number of cycles OR MDS/MPN relapsed/refractory following treatment with hydroxyurea OR at least 4 cycles of azacytidine, decitabine, guadecitabine or ASTX727 or relapse or progression after any number of cycles or who are intolerant of treatment with hydroxiurea.",
            "criterions": [
                {
                    "exact_snippets": "MDS participants with no response after 4 cycles of azacitidine, decitabine, guadecitabine, CC-486 or ASTX727",
                    "criterion": "MDS participants",
                    "requirements": [
                        {
                            "requirement_type": "treatment response",
                            "expected_value": "no response after 4 cycles of azacitidine, decitabine, guadecitabine, CC-486 or ASTX727"
                        }
                    ]
                },
                {
                    "exact_snippets": "MDS participants with ... relapse or progression after any number of cycles",
                    "criterion": "MDS participants",
                    "requirements": [
                        {
                            "requirement_type": "disease status",
                            "expected_value": "relapse or progression after any number of cycles"
                        }
                    ]
                },
                {
                    "exact_snippets": "MDS/MPN relapsed/refractory following treatment with hydroxyurea",
                    "criterion": "MDS/MPN participants",
                    "requirements": [
                        {
                            "requirement_type": "disease status",
                            "expected_value": "relapsed/refractory following treatment with hydroxyurea"
                        }
                    ]
                },
                {
                    "exact_snippets": "MDS/MPN ... who are intolerant of treatment with hydroxiurea",
                    "criterion": "MDS/MPN participants",
                    "requirements": [
                        {
                            "requirement_type": "treatment tolerance",
                            "expected_value": "intolerant of treatment with hydroxiurea"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Phase 2 dose expansion cohort:",
            "criterions": [
                {
                    "exact_snippets": "Phase 2 dose expansion cohort",
                    "criterion": "trial phase",
                    "requirements": [
                        {
                            "requirement_type": "phase",
                            "expected_value": "Phase 2"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Relapsed MDS cohort (Cohort B): no response after 4 cycles of azacitidine, decitabine, guadecitabine or ASTX727 or relapse or progression after any number of cycles.",
            "criterions": [
                {
                    "exact_snippets": "no response after 4 cycles of azacitidine, decitabine, guadecitabine or ASTX727",
                    "criterion": "response to treatment",
                    "requirements": [
                        {
                            "requirement_type": "response",
                            "expected_value": "no response"
                        },
                        {
                            "requirement_type": "treatment duration",
                            "expected_value": {
                                "operator": "=",
                                "value": 4,
                                "unit": "cycles"
                            }
                        },
                        {
                            "requirement_type": "treatment type",
                            "expected_value": [
                                "azacitidine",
                                "decitabine",
                                "guadecitabine",
                                "ASTX727"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "relapse or progression after any number of cycles",
                    "criterion": "disease status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": [
                                "relapse",
                                "progression"
                            ]
                        },
                        {
                            "requirement_type": "treatment duration",
                            "expected_value": "any number of cycles"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Relapsed MDS/MPN cohort (Cohort C): relapsed/refractory following treatment with hydroxyurea or at least 4 cycles of azacytidine, decitabine, guadecitabine or ASTX727 or relapse or progression after any number of cycles or who are intolerant of treatment with wih hydroxiurea.",
            "criterions": [
                {
                    "exact_snippets": "relapsed/refractory following treatment with hydroxyurea",
                    "criterion": "relapsed/refractory status",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "hydroxyurea"
                        }
                    ]
                },
                {
                    "exact_snippets": "relapsed/refractory following treatment with ... at least 4 cycles of azacytidine, decitabine, guadecitabine or ASTX727",
                    "criterion": "relapsed/refractory status",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": [
                                "azacytidine",
                                "decitabine",
                                "guadecitabine",
                                "ASTX727"
                            ]
                        },
                        {
                            "requirement_type": "treatment cycles",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "cycles"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "relapse or progression after any number of cycles",
                    "criterion": "relapse or progression status",
                    "requirements": [
                        {
                            "requirement_type": "treatment cycles",
                            "expected_value": "any number"
                        }
                    ]
                },
                {
                    "exact_snippets": "intolerant of treatment with wih hydroxiurea",
                    "criterion": "treatment intolerance",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "hydroxyurea"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known mutation in genes leading to RAS pathway activation (NRAS, KRAS, BRAF, CBL, NF1, PTPN11).",
            "criterions": [
                {
                    "exact_snippets": "Known mutation in genes leading to RAS pathway activation (NRAS, KRAS, BRAF, CBL, NF1, PTPN11)",
                    "criterion": "mutation in genes",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "genes",
                            "expected_value": [
                                "NRAS",
                                "KRAS",
                                "BRAF",
                                "CBL",
                                "NF1",
                                "PTPN11"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Creatinine clearance ≥30ml/min based on the Cockcroft-Gault Glomerular Filtration Rate estimation.",
            "criterions": [
                {
                    "exact_snippets": "Creatinine clearance ≥30ml/min",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 30,
                                "unit": "ml/min"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate hepatic function with total bilirubin ≤1.5x ULN, AST or ALT ≤3 xULN.",
            "criterions": [
                {
                    "exact_snippets": "Adequate hepatic function with total bilirubin ≤1.5x ULN",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate hepatic function with ... AST or ALT ≤3 xULN",
                    "criterion": "AST or ALT",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* ECOG Performance Status 0-2.",
            "criterions": [
                {
                    "exact_snippets": "ECOG Performance Status 0-2",
                    "criterion": "ECOG Performance Status",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participant (or patient's legally authorized representative) must have signed an informed consent document indicating that the participant understands the purpose of and procedures required for the study and is willing to participate in the study. Non-English speaking participants may be consented.",
            "criterions": [
                {
                    "exact_snippets": "Participant (or patient's legally authorized representative) must have signed an informed consent document",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "signed",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "indicating that the participant understands the purpose of and procedures required for the study",
                    "criterion": "understanding of study purpose and procedures",
                    "requirements": [
                        {
                            "requirement_type": "understanding",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "is willing to participate in the study",
                    "criterion": "willingness to participate",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Non-English speaking participants may be consented",
                    "criterion": "language of participant",
                    "requirements": [
                        {
                            "requirement_type": "language",
                            "expected_value": "Non-English"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prior hydroxyurea for control of leukocytosis or use of hematopoietic growth factors (eg, G-CSF, GM-CSF, procrit, aranesp, thrombopoietins) is allowed at any time prior to cycle 1 day 1 of therapy.",
            "criterions": [
                {
                    "exact_snippets": "Prior hydroxyurea for control of leukocytosis",
                    "criterion": "prior hydroxyurea use",
                    "requirements": [
                        {
                            "requirement_type": "purpose",
                            "expected_value": "control of leukocytosis"
                        }
                    ]
                },
                {
                    "exact_snippets": "use of hematopoietic growth factors (eg, G-CSF, GM-CSF, procrit, aranesp, thrombopoietins) is allowed",
                    "criterion": "use of hematopoietic growth factors",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "at any time prior to cycle 1 day 1 of therapy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.",
            "criterions": [
                {
                    "exact_snippets": "evidence of chronic hepatitis B virus (HBV) infection",
                    "criterion": "chronic hepatitis B virus (HBV) infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "HBV viral load must be undetectable",
                    "criterion": "HBV viral load",
                    "requirements": [
                        {
                            "requirement_type": "detectability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "on suppressive therapy, if indicated",
                    "criterion": "suppressive therapy",
                    "requirements": [
                        {
                            "requirement_type": "indication",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.",
            "criterions": [
                {
                    "exact_snippets": "history of hepatitis C virus (HCV) infection must have been treated and cured",
                    "criterion": "history of hepatitis C virus (HCV) infection",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "treated and cured"
                        }
                    ]
                },
                {
                    "exact_snippets": "HCV infection who are currently on treatment ... undetectable HCV viral load",
                    "criterion": "HCV infection",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "currently on treatment"
                        },
                        {
                            "requirement_type": "viral load",
                            "expected_value": "undetectable"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. The effects of ASTX029 on the developing human fetus are unknown. For this reason and because 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 and for the duration of study participation. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). This includes all female participants, between the onset of menses (as early as 8 years of age) and 55 years unless the participant presents with an applicable exclusionary factor which may be one of the following:",
            "criterions": [
                {
                    "exact_snippets": "Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen",
                    "criterion": "prior or concurrent malignancy",
                    "requirements": [
                        {
                            "requirement_type": "interference with safety or efficacy assessment",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "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 and for the duration of study participation",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "all female participants, between the onset of menses (as early as 8 years of age) and 55 years",
                    "criterion": "female age",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 8,
                                        "unit": "years"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 55,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Postmenopausal (no menses in greater than or equal to 12 consecutive months).",
            "criterions": [
                {
                    "exact_snippets": "Postmenopausal (no menses in greater than or equal to 12 consecutive months)",
                    "criterion": "menstrual status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "postmenopausal"
                        }
                    ]
                },
                {
                    "exact_snippets": "no menses in greater than or equal to 12 consecutive months",
                    "criterion": "menses",
                    "requirements": [
                        {
                            "requirement_type": "absence duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of hysterectomy or bilateral salpingo-oophorectomy.",
            "criterions": [
                {
                    "exact_snippets": "History of hysterectomy",
                    "criterion": "hysterectomy",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "History of ... bilateral salpingo-oophorectomy",
                    "criterion": "bilateral salpingo-oophorectomy",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).",
            "criterions": [
                {
                    "exact_snippets": "Ovarian failure",
                    "criterion": "ovarian failure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Follicle Stimulating Hormone ... in menopausal range",
                    "criterion": "Follicle Stimulating Hormone",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": "menopausal range"
                        }
                    ]
                },
                {
                    "exact_snippets": "Estradiol in menopausal range",
                    "criterion": "Estradiol",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": "menopausal range"
                        }
                    ]
                },
                {
                    "exact_snippets": "who have received Whole Pelvic Radiation Therapy",
                    "criterion": "Whole Pelvic Radiation Therapy",
                    "requirements": [
                        {
                            "requirement_type": "receipt",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of bilateral tubal ligation or another surgical sterilization procedure.",
            "criterions": [
                {
                    "exact_snippets": "History of bilateral tubal ligation",
                    "criterion": "bilateral tubal ligation",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "another surgical sterilization procedure",
                    "criterion": "surgical sterilization procedure",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. 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": "Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide.",
                    "criterion": "birth control method",
                    "requirements": [
                        {
                            "requirement_type": "approved methods",
                            "expected_value": [
                                "Hormonal contraception",
                                "Intrauterine device (IUD)",
                                "Tubal Ligation",
                                "hysterectomy",
                                "Subject/Partner post vasectomy",
                                "Implantable or injectable contraceptives",
                                "condoms plus spermicide"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice",
                    "criterion": "sexual activity",
                    "requirements": [
                        {
                            "requirement_type": "engagement",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control",
                    "criterion": "birth control method",
                    "requirements": [
                        {
                            "requirement_type": "unacceptable methods",
                            "expected_value": [
                                "periodic abstinence",
                                "rhythm method",
                                "withdrawal method"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "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.",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "notification",
                            "expected_value": "inform treating physician immediately"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of ASTX727 and ASTX029 administration.",
            "criterions": [
                {
                    "exact_snippets": "Men treated or enrolled on this protocol must also agree to use adequate contraception",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "prior to the study, for the duration of study participation, and 4 months after completion of ASTX727 and ASTX029 administration",
                    "criterion": "contraception use duration",
                    "requirements": [
                        {
                            "requirement_type": "time period",
                            "expected_value": "prior to the study, for the duration of study participation, and 4 months after completion of ASTX727 and ASTX029 administration"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Ability to understand and the willingness to sign a written informed consent document.",
            "criterions": [
                {
                    "exact_snippets": "Ability to understand",
                    "criterion": "cognitive ability",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "willingness to sign a written informed consent document",
                    "criterion": "willingness to consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have minimum age of 18 Years",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 18 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "* Participants who are currently receiving treatment for a malignancy (not including basal cell carcinoma, nonmelanoma skin cancer, cervical carcinoma in situ, early stage breast cancer or localized prostate cancer treated with hormone therapy). Participants with history of other cancers should be free of disease for at least 2 years prior to the Screening Visit or not requiring active treatment at the time of enrollment.",
            "criterions": [
                {
                    "exact_snippets": "Participants who are currently receiving treatment for a malignancy",
                    "criterion": "current treatment for malignancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Participants who are currently receiving treatment for a malignancy ... not including basal cell carcinoma, nonmelanoma skin cancer, cervical carcinoma in situ, early stage breast cancer or localized prostate cancer treated with hormone therapy",
                    "criterion": "current treatment for specific cancers",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "cancer types",
                            "expected_value": [
                                "basal cell carcinoma",
                                "nonmelanoma skin cancer",
                                "cervical carcinoma in situ",
                                "early stage breast cancer",
                                "localized prostate cancer treated with hormone therapy"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Participants with history of other cancers should be free of disease for at least 2 years prior to the Screening Visit",
                    "criterion": "disease-free period for history of other cancers",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Participants with history of other cancers ... or not requiring active treatment at the time of enrollment",
                    "criterion": "active treatment requirement for history of other cancers",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 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": "* Participants who have an active, life-threatening, or clinically-significant uncontrolled systemic infection requiring hospitalization.",
            "criterions": [
                {
                    "exact_snippets": "active, life-threatening, or clinically-significant uncontrolled systemic infection",
                    "criterion": "systemic infection",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": [
                                "active",
                                "life-threatening",
                                "clinically-significant",
                                "uncontrolled"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "requiring hospitalization",
                    "criterion": "hospitalization",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participants who have a known malabsorption syndrome or other condition that may impair absorption of study medication (e.g., gastrectomy).",
            "criterions": [
                {
                    "exact_snippets": "known malabsorption syndrome",
                    "criterion": "malabsorption syndrome",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "other condition that may impair absorption of study medication",
                    "criterion": "condition impairing absorption",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Pregnant women are excluded from this study because ASTX029 and ASTX727 are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is treated on study. These potential risks may also apply to other agents used in this study.",
            "criterions": [
                {
                    "exact_snippets": "Pregnant women are excluded",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "breastfeeding should be discontinued if the mother is treated on study",
                    "criterion": "breastfeeding",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participants with reproductive potential who are unwilling to following contraception requirements (including condom use for males with sexual partners, and for females: prescription oral contraceptives [birth control pills], contraceptive injections, intrauterine devices [IUD], double-barrier method [spermicidal jelly or foam with condoms or diaphragm], contraceptive patch, or surgical sterilization) throughout the study.",
            "criterions": [
                {
                    "exact_snippets": "Participants with reproductive potential",
                    "criterion": "reproductive potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "unwilling to following contraception requirements",
                    "criterion": "willingness to follow contraception requirements",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "contraception requirements (including condom use for males with sexual partners, and for females: prescription oral contraceptives [birth control pills], contraceptive injections, intrauterine devices [IUD], double-barrier method [spermicidal jelly or foam with condoms or diaphragm], contraceptive patch, or surgical sterilization)",
                    "criterion": "contraception methods",
                    "requirements": [
                        {
                            "requirement_type": "methods",
                            "expected_value": [
                                "condom use for males",
                                "prescription oral contraceptives",
                                "contraceptive injections",
                                "intrauterine devices",
                                "double-barrier method",
                                "contraceptive patch",
                                "surgical sterilization"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Female participants with reproductive potential who do not have a negative urine or blood beta-human chorionic gonadotropin (beta HCG) pregnancy test at screening.",
            "criterions": [
                {
                    "exact_snippets": "Female participants",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "expected gender",
                            "expected_value": "female"
                        }
                    ]
                },
                {
                    "exact_snippets": "reproductive potential",
                    "criterion": "reproductive potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "do not have a negative urine or blood beta-human chorionic gonadotropin (beta HCG) pregnancy test",
                    "criterion": "beta HCG pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "at screening",
                    "criterion": "screening",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "at screening"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participants receiving any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy within 7 days of therapy initiation.",
            "criterions": [
                {
                    "exact_snippets": "Participants receiving any other concurrent investigational agent",
                    "criterion": "concurrent investigational agent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Participants receiving any other concurrent ... chemotherapy",
                    "criterion": "concurrent chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Participants receiving any other concurrent ... radiotherapy",
                    "criterion": "concurrent radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Participants receiving any other concurrent ... immunotherapy",
                    "criterion": "concurrent immunotherapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "within 7 days of therapy initiation",
                    "criterion": "time since last therapy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "<",
                                "value": 7,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participants known to be positive for hepatitis B surface antigen expression or with active hepatitis C infection (positive by polymerase chain reaction or on antiviral therapy for hepatitis C within the last 6 months).",
            "criterions": [
                {
                    "exact_snippets": "positive for hepatitis B surface antigen expression",
                    "criterion": "hepatitis B surface antigen expression",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "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": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participants with history of HIV with CD4+ T-cell (CD4+) counts <350 cell/mcL or with AIDS-defining opportunistic infections in the last 12 months are also excluded. Participants with well controlled HIV (defined as CD4+ counts >350 cells/mcL with undetectable viral load prior to enrollment with no AIDS-defining opportunistic infections in the past 12 months) on therapy with antiretroviral therapies known to be metabolites of cytochrome P450 (CYP3A4) enzymes will also be excluded.",
            "criterions": [
                {
                    "exact_snippets": "history of HIV",
                    "criterion": "HIV history",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "CD4+ T-cell (CD4+) counts <350 cell/mcL",
                    "criterion": "CD4+ T-cell count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<",
                                "value": 350,
                                "unit": "cell/mcL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "AIDS-defining opportunistic infections in the last 12 months",
                    "criterion": "AIDS-defining opportunistic infections",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": "last 12 months"
                        }
                    ]
                },
                {
                    "exact_snippets": "well controlled HIV (defined as CD4+ counts >350 cells/mcL with undetectable viral load",
                    "criterion": "HIV control",
                    "requirements": [
                        {
                            "requirement_type": "CD4+ count",
                            "expected_value": {
                                "operator": ">",
                                "value": 350,
                                "unit": "cells/mcL"
                            }
                        },
                        {
                            "requirement_type": "viral load",
                            "expected_value": "undetectable"
                        }
                    ]
                },
                {
                    "exact_snippets": "no AIDS-defining opportunistic infections in the past 12 months",
                    "criterion": "AIDS-defining opportunistic infections",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": "past 12 months"
                        }
                    ]
                },
                {
                    "exact_snippets": "therapy with antiretroviral therapies known to be metabolites of cytochrome P450 (CYP3A4) enzymes",
                    "criterion": "antiretroviral therapy metabolism",
                    "requirements": [
                        {
                            "requirement_type": "metabolism",
                            "expected_value": "cytochrome P450 (CYP3A4) enzymes"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participants with QTc interval >480 msec based on average of triplicate ECG readings at the Screening Visit using the Fridericia formula (QTcF), with the exception of participants with right bundle branch block or left bundle branch block.",
            "criterions": [
                {
                    "exact_snippets": "QTc interval >480 msec ... average of triplicate ECG readings ... Screening Visit ... Fridericia formula (QTcF)",
                    "criterion": "QTc interval",
                    "requirements": [
                        {
                            "requirement_type": "measurement",
                            "expected_value": {
                                "operator": ">",
                                "value": 480,
                                "unit": "msec"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "right bundle branch block",
                    "criterion": "right bundle branch block",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "left bundle branch block",
                    "criterion": "left bundle branch block",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* New York Heart Association (NYHA) Class III or IV congestive heart failure or LVEF <50 by echocardiogram or multigated acquisition (MUGA) scan.",
            "criterions": [
                {
                    "exact_snippets": "New York Heart Association (NYHA) Class III or IV congestive heart failure",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "NYHA Class III",
                                "NYHA Class IV"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "LVEF <50 by echocardiogram or multigated acquisition (MUGA) scan",
                    "criterion": "left ventricular ejection fraction (LVEF)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<",
                                "value": 50,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of myocardial infarction within the last 6 months or unstable/uncontrolled angina pectoris or history of severe and/or uncontrolled ventricular arrhythmias.",
            "criterions": [
                {
                    "exact_snippets": "History of myocardial infarction within the last 6 months",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "unstable/uncontrolled angina pectoris",
                    "criterion": "angina pectoris",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": "unstable/uncontrolled"
                        }
                    ]
                },
                {
                    "exact_snippets": "history of severe and/or uncontrolled ventricular arrhythmias",
                    "criterion": "ventricular arrhythmias",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        },
                        {
                            "requirement_type": "control",
                            "expected_value": "uncontrolled"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participants with psychiatric illness/social situations that would limit compliance with study requirements.",
            "criterions": [
                {
                    "exact_snippets": "psychiatric illness",
                    "criterion": "psychiatric illness",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "social situations that would limit compliance with study requirements",
                    "criterion": "social situations",
                    "requirements": [
                        {
                            "requirement_type": "impact on compliance",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}