{
    "info": {
        "nct_id": "NCT03064867",
        "official_title": "Phase I/II Trial of Venetoclax in Combination With R-ICE (V+RICE) Chemotherapy for Relapsed/Refractory Diffuse Large B-Cell Lymphoma",
        "inclusion_criteria": "* Histological confirmation of relapsed/refractory diffuse large B-cell lymphoma after prior rituximab and anthracycline-containing systemic treatment regimen such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), R-EPOCH (rituximab, etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, doxorubicin hydrochloride), R-HyperCVAD (rituximab, cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, dexamethasone) etc. A biopsy immediately before enrollment is not required.\n* Subjects must have received no more than 2 prior systemic therapies for lymphoma. Prior therapy with systemic rituximab monotherapy or conventional chemotherapy (i.e. bendamustine, CVP (Cyclophosphamide, Vincristine Sulfate, Prednisone) or other) ± rituximab for indolent non-Hodgkin's lymphoma (NHL) ± maintenance/extended-use rituximab will count as 1 line of systemic therapy.\n* Eastern Cooperative Oncology Group (ECOG) Performance status ≤ 2\n* Subjects must have normal organ and marrow function as defined below:\n\n  * Hemoglobin ≥ 8.0 g/dl\n  * Absolute neutrophil count ≥ 1,000/mcL\n  * Platelet count ≥ 75,000/mcL\n  * Total bilirubin ≤ 1.5 X the upper limit of normal (ULN) unless a known history of impaired bilirubin conjugation such as Gilbert's, for whom the maximum will be 2.5 ULN.\n  * Aspartate transaminase (AST) (SGOT) ≤ 2.5 X institutional ULN\n  * Alanine transaminase (ALT) (SGPT) ≤ 2.5 X institutional ULN\n  * International normalized ratio (INR) ≤ 1.5 ×ULN\n  * Patients must have a calculated serum creatinine clearance > 50 mL/min using Cockcroft-Gault calculation or based on 24-hour urine collection performed within 7 days prior to treatment.\n* Specific guidelines will be followed regarding inclusion of relapsed/refractory DLBCL based on Hepatitis B serological testing as follow:\n\n  * HBsAg negative, HBcAb negative, HBsAb negative patients are eligible.\n  * HBsAg negative, HBcAb negative, HBsAb positive patients are eligible.\n  * Patients who test positive for HBsAg are ineligible\n  * Patients with HBsAg negative, but HBcAb positive (regardless of HBsAb status) should have a HBV DNA testing performed and protocol eligibility determined as follow:\n\n    * If HBV DNA is positive, the subject is ineligible.\n    * If HBV DNA is negative, the subject may be included but must undergo HBV DNA PCR testing monthly x 3 months beginning from the start of treatment\n* Subjects must have the ability to understand and the willingness to sign a written informed consent document.\n* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of < 1% per year during the treatment period and for at least 30 days after the last dose of venetoclax or 18 months after the last dose of rituximab, whichever is longer.\n\nA woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (< 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).\n\n* For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:\n\nWith female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for at least 6 months after the last dose of rituximab. Men must refrain from donating sperm during this same period.\n\nWith pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 6 months after the last dose of rituximab to avoid exposing the embryo.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Prior treatment toxicities have not resolved to ≤ Grade 2 according to NCI CTCAE Version 4.0 (except clinically insignificant toxicities such as alopecia).\n* Subjects receiving any other investigational agents.\n* Patients with active tumor lysis syndrome (TLS) either from laboratory or clinical changes.\n* Patients with active central nervous system (CNS) disease defined as symptomatic meningeal lymphoma or known CNS parenchymal lymphoma.\n* History of severe allergic reactions attributed to compounds of similar chemical or biologic composition to rituximab or other agents used in this study.\n* Subjects with uncontrolled intercurrent illness .\n* HIV-positive subjects on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Venetoclax. In addition, these subjects are at increased risk of lethal infections when treated with marrow suppressive therapy. Appropriate studies will be undertaken in subjects receiving combination antiretroviral therapy when indicated. HIV testing prior to enrollment is not required for screening but strongly encouraged for patients with no documented prior HIV assessment.\n* Presence of positive test results for hepatitis B virus (HBV), hepatitis B surface antigen (HBsAg), or hepatitis C (HCV) antibody.\n\n  * Patients who are positive for HCV antibody must be negative for HCV by polymerase chain reaction (PCR) to be eligible for study participation\n  * Patients with occult or prior HBV infection (defined as positive total hepatitis B core antibody [HBcAb] and negative HBsAg) may be included if HBV DNA is undetectable. These patients must be willing to undergo monthly DNA testing.\n* Women who are pregnant or lactating\n* Malabsorption syndrome or other condition that precludes enteral route of administration\n* Chemotherapy or radiation within 3 weeks of the first scheduled study treatment.\n* Less than 2-year disease free from another primary malignancy (other than squamous or basal cell carcinoma of the skin, \"in-situ\" carcinoma of the cervix or breast, superficial bladder carcinoma, or previously treated localized prostate cancer with normal prostate specific antigen (PSA) levels). Patients who have had completed all anti-cancer treatment for another primary malignancy more than 2 years prior to screening are eligible if they are not considered to have a \"currently active\" malignancy based on having less than a 30% risk of relapse.\n* Major surgery, other than diagnostic surgery, within 2 weeks.\n* Medical condition requiring chronic use of high dose systemic corticosteroids (i.e., doses of prednisone higher than 10 mg/day or equivalent). Brief (<15 days) treatment with glucocorticoids (prednisone 100 mg by mouth daily, or equivalent) is acceptable.\n* Known allergy to both xanthine oxidase inhibitors and rasburicase.\n* Use of warfarin is prohibited. Anticoagulation with low-molecular weight heparin (i.e. enoxaparin) or direct thrombin inhibitors is permitted.\n* The following concomitant medications are not allowed from 7 days prior to the first dose of study drug and during venetoclax administration: Strong CYP3A4 inhibitors including but not limited to fluconazole, ketoconazole, and clarithromycin or strong CYP3A4 inducers included but not limited to rifampin, carbamazepine.\n* Receipt of live-virus vaccines within 28 days prior to the initiation of study treatment or need for live-virus vaccines at any time during study treatment.\n* Concomitant medications that fall into the categories below could potentially lead to adverse reactions and should be considered with caution.\n\n  * Moderate/Weak CYP3A inducers such as efavirenz and oxcarbazepine\n  * CYP2C8 substrates such as thiazolidinediones (glitazones) and select statins (because of expected inhibition of the metabolism of CYP2C8 substrates) by venetoclax\n  * CYP2C9 substrates such as tolbutamide (because of expected inhibition of the metabolism of CYP2C9 substrates by venetoclax. It is recommended to exclude CYP2C9 substrates with a narrow therapeutic index such as phenytoin.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Histological confirmation of relapsed/refractory diffuse large B-cell lymphoma after prior rituximab and anthracycline-containing systemic treatment regimen such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), R-EPOCH (rituximab, etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, doxorubicin hydrochloride), R-HyperCVAD (rituximab, cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, dexamethasone) etc. A biopsy immediately before enrollment is not required.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Histological confirmation of relapsed/refractory diffuse large B-cell lymphoma"
                    ],
                    "criterion": "diffuse large B-cell lymphoma",
                    "requirement_type": "confirmation",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "after prior rituximab and anthracycline-containing systemic treatment regimen"
                    ],
                    "criterion": "rituximab and anthracycline-containing systemic treatment regimen",
                    "requirement_type": "prior treatment",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "A biopsy immediately before enrollment is not required"
                    ],
                    "criterion": "biopsy immediately before enrollment",
                    "requirement_type": "requirement",
                    "expected_value": false
                }
            ]
        },
        {
            "line": "* Subjects must have received no more than 2 prior systemic therapies for lymphoma. Prior therapy with systemic rituximab monotherapy or conventional chemotherapy (i.e. bendamustine, CVP (Cyclophosphamide, Vincristine Sulfate, Prednisone) or other) ± rituximab for indolent non-Hodgkin's lymphoma (NHL) ± maintenance/extended-use rituximab will count as 1 line of systemic therapy.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Subjects must have received no more than 2 prior systemic therapies for lymphoma"
                    ],
                    "criterion": "prior systemic therapies for lymphoma",
                    "requirement_type": "quantity",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 2
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "Prior therapy with systemic rituximab monotherapy or conventional chemotherapy (i.e. bendamustine, CVP (Cyclophosphamide, Vincristine Sulfate, Prednisone) or other) ± rituximab for indolent non-Hodgkin's lymphoma (NHL) ± maintenance/extended-use rituximab will count as 1 line of systemic therapy"
                    ],
                    "criterion": "prior therapy",
                    "requirement_type": "type",
                    "expected_value": [
                        "systemic rituximab monotherapy",
                        "conventional chemotherapy",
                        "bendamustine",
                        "CVP",
                        "Cyclophosphamide",
                        "Vincristine Sulfate",
                        "Prednisone",
                        "rituximab",
                        "indolent non-Hodgkin's lymphoma",
                        "NHL",
                        "maintenance/extended-use rituximab"
                    ]
                }
            ]
        },
        {
            "line": "* Eastern Cooperative Oncology Group (ECOG) Performance status ≤ 2",
            "criterions": [
                {
                    "exact_snippets": [
                        "Eastern Cooperative Oncology Group (ECOG) Performance status ≤ 2"
                    ],
                    "criterion": "ECOG Performance status",
                    "requirement_type": "severity",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 2
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Subjects must have normal organ and marrow function as defined below:",
            "criterions": [
                {
                    "exact_snippets": [
                        "normal organ and marrow function"
                    ],
                    "criterion": "organ function",
                    "requirement_type": "status",
                    "expected_value": "normal"
                },
                {
                    "exact_snippets": [
                        "normal organ and marrow function"
                    ],
                    "criterion": "marrow function",
                    "requirement_type": "status",
                    "expected_value": "normal"
                }
            ]
        },
        {
            "line": "* Hemoglobin ≥ 8.0 g/dl",
            "criterions": [
                {
                    "exact_snippets": [
                        "Hemoglobin ≥ 8.0 g/dl"
                    ],
                    "criterion": "hemoglobin",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 8.0
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Absolute neutrophil count ≥ 1,000/mcL",
            "criterions": [
                {
                    "exact_snippets": [
                        "Absolute neutrophil count ≥ 1,000/mcL"
                    ],
                    "criterion": "absolute neutrophil count",
                    "requirement_type": "quantity",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 1000
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Platelet count ≥ 75,000/mcL",
            "criterions": [
                {
                    "exact_snippets": [
                        "Platelet count ≥ 75,000/mcL"
                    ],
                    "criterion": "platelet",
                    "requirement_type": "count",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 75000
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Total bilirubin ≤ 1.5 X the upper limit of normal (ULN) unless a known history of impaired bilirubin conjugation such as Gilbert's, for whom the maximum will be 2.5 ULN.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Total bilirubin",
                        "≤ 1.5 X the upper limit of normal (ULN)"
                    ],
                    "criterion": "total bilirubin",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 1.5
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "known history of impaired bilirubin conjugation such as Gilbert's"
                    ],
                    "criterion": "impaired bilirubin conjugation",
                    "requirement_type": "history",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "Total bilirubin",
                        "maximum will be 2.5 ULN"
                    ],
                    "criterion": "total bilirubin",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 2.5
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Aspartate transaminase (AST) (SGOT) ≤ 2.5 X institutional ULN",
            "criterions": [
                {
                    "exact_snippets": [
                        "Aspartate transaminase (AST) (SGOT)",
                        "≤ 2.5 X institutional ULN"
                    ],
                    "criterion": "Aspartate transaminase (AST) (SGOT)",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 2.5
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Alanine transaminase (ALT) (SGPT) ≤ 2.5 X institutional ULN",
            "criterions": [
                {
                    "exact_snippets": [
                        "Alanine transaminase (ALT) (SGPT) ≤ 2.5 X institutional ULN"
                    ],
                    "criterion": "Alanine transaminase (ALT) (SGPT)",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 2.5
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* International normalized ratio (INR) ≤ 1.5 ×ULN",
            "criterions": [
                {
                    "exact_snippets": [
                        "International normalized ratio (INR) ≤ 1.5 ×ULN"
                    ],
                    "criterion": "international normalized ratio (INR)",
                    "requirement_type": "value",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 1.5
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Patients must have a calculated serum creatinine clearance > 50 mL/min using Cockcroft-Gault calculation or based on 24-hour urine collection performed within 7 days prior to treatment.",
            "criterions": [
                {
                    "exact_snippets": [
                        "calculated serum creatinine clearance > 50 mL/min"
                    ],
                    "criterion": "serum creatinine clearance",
                    "requirement_type": "quantity",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">",
                                "value": 50
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "using Cockcroft-Gault calculation"
                    ],
                    "criterion": "Cockcroft-Gault calculation",
                    "requirement_type": "method",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "based on 24-hour urine collection"
                    ],
                    "criterion": "24-hour urine collection",
                    "requirement_type": "method",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "performed within 7 days prior to treatment"
                    ],
                    "criterion": "test timing",
                    "requirement_type": "timing",
                    "expected_value": "within 7 days prior to treatment"
                }
            ]
        },
        {
            "line": "* Specific guidelines will be followed regarding inclusion of relapsed/refractory DLBCL based on Hepatitis B serological testing as follow:",
            "criterions": [
                {
                    "exact_snippets": [
                        "relapsed/refractory DLBCL"
                    ],
                    "criterion": "DLBCL",
                    "requirement_type": "status",
                    "expected_value": [
                        "relapsed",
                        "refractory"
                    ]
                },
                {
                    "exact_snippets": [
                        "Hepatitis B serological testing"
                    ],
                    "criterion": "Hepatitis B",
                    "requirement_type": "serological testing",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "* HBsAg negative, HBcAb negative, HBsAb negative patients are eligible.",
            "criterions": [
                {
                    "exact_snippets": [
                        "HBsAg negative"
                    ],
                    "criterion": "HBsAg",
                    "requirement_type": "presence",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "HBcAb negative"
                    ],
                    "criterion": "HBcAb",
                    "requirement_type": "presence",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "HBsAb negative"
                    ],
                    "criterion": "HBsAb",
                    "requirement_type": "presence",
                    "expected_value": false
                }
            ]
        },
        {
            "line": "* HBsAg negative, HBcAb negative, HBsAb positive patients are eligible.",
            "criterions": [
                {
                    "exact_snippets": [
                        "HBsAg negative"
                    ],
                    "criterion": "HBsAg",
                    "requirement_type": "presence",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "HBcAb negative"
                    ],
                    "criterion": "HBcAb",
                    "requirement_type": "presence",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "HBsAb positive"
                    ],
                    "criterion": "HBsAb",
                    "requirement_type": "presence",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "* Patients who test positive for HBsAg are ineligible",
            "criterions": [
                {
                    "exact_snippets": [
                        "test positive for HBsAg"
                    ],
                    "criterion": "HBsAg",
                    "requirement_type": "presence",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "* Patients with HBsAg negative, but HBcAb positive (regardless of HBsAb status) should have a HBV DNA testing performed and protocol eligibility determined as follow:",
            "criterions": [
                {
                    "exact_snippets": [
                        "HBsAg negative"
                    ],
                    "criterion": "HBsAg",
                    "requirement_type": "status",
                    "expected_value": "negative"
                },
                {
                    "exact_snippets": [
                        "HBcAb positive"
                    ],
                    "criterion": "HBcAb",
                    "requirement_type": "status",
                    "expected_value": "positive"
                },
                {
                    "exact_snippets": [
                        "HBV DNA testing performed"
                    ],
                    "criterion": "HBV DNA testing",
                    "requirement_type": "action",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "* If HBV DNA is positive, the subject is ineligible.",
            "criterions": [
                {
                    "exact_snippets": [
                        "HBV DNA is positive"
                    ],
                    "criterion": "HBV DNA",
                    "requirement_type": "presence",
                    "expected_value": false
                }
            ]
        },
        {
            "line": "* If HBV DNA is negative, the subject may be included but must undergo HBV DNA PCR testing monthly x 3 months beginning from the start of treatment",
            "criterions": [
                {
                    "exact_snippets": [
                        "HBV DNA is negative"
                    ],
                    "criterion": "HBV DNA",
                    "requirement_type": "status",
                    "expected_value": "negative"
                }
            ]
        },
        {
            "line": "* Subjects must have the ability to understand and the willingness to sign a written informed consent document.",
            "criterions": [
                {
                    "exact_snippets": [
                        "ability to understand"
                    ],
                    "criterion": "understanding ability",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "willingness to sign a written informed consent document"
                    ],
                    "criterion": "willingness to sign consent",
                    "requirement_type": "presence",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of < 1% per year during the treatment period and for at least 30 days after the last dose of venetoclax or 18 months after the last dose of rituximab, whichever is longer.",
            "criterions": [
                {
                    "exact_snippets": [
                        "women of childbearing potential"
                    ],
                    "criterion": "childbearing potential",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method"
                    ],
                    "criterion": "contraceptive method",
                    "requirement_type": "failure rate",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<",
                                "value": 1
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "during the treatment period and for at least 30 days after the last dose of venetoclax or 18 months after the last dose of rituximab, whichever is longer"
                    ],
                    "criterion": "contraceptive method",
                    "requirement_type": "duration",
                    "expected_value": "during treatment and for at least 30 days after venetoclax or 18 months after rituximab, whichever is longer"
                }
            ]
        },
        {
            "line": "A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (< 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).",
            "criterions": [
                {
                    "exact_snippets": [
                        "postmenarcheal"
                    ],
                    "criterion": "menarcheal status",
                    "requirement_type": "state",
                    "expected_value": "postmenarcheal"
                },
                {
                    "exact_snippets": [
                        "postmenopausal state",
                        "< 12 continuous months of amenorrhea with no identified cause other than menopause"
                    ],
                    "criterion": "menopausal state",
                    "requirement_type": "state",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "surgical sterilization",
                        "removal of ovaries and/or uterus"
                    ],
                    "criterion": "surgical sterilization",
                    "requirement_type": "procedure",
                    "expected_value": false
                }
            ]
        },
        {
            "line": "With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for at least 6 months after the last dose of rituximab. Men must refrain from donating sperm during this same period.",
            "criterions": [
                {
                    "exact_snippets": [
                        "female partners of childbearing potential"
                    ],
                    "criterion": "female partners",
                    "requirement_type": "childbearing potential",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "men must remain abstinent or use a condom plus an additional contraceptive method"
                    ],
                    "criterion": "contraceptive method",
                    "requirement_type": "use",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "that together result in a failure rate of < 1% per year"
                    ],
                    "criterion": "contraceptive method failure rate",
                    "requirement_type": "rate",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<",
                                "value": 1
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "during the treatment period and for at least 6 months after the last dose of rituximab"
                    ],
                    "criterion": "contraceptive method duration",
                    "requirement_type": "duration",
                    "expected_value": "treatment period and for at least 6 months after the last dose of rituximab"
                },
                {
                    "exact_snippets": [
                        "Men must refrain from donating sperm"
                    ],
                    "criterion": "sperm donation",
                    "requirement_type": "refrain",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "during this same period"
                    ],
                    "criterion": "sperm donation duration",
                    "requirement_type": "duration",
                    "expected_value": "treatment period and for at least 6 months after the last dose of rituximab"
                }
            ]
        },
        {
            "line": "With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 6 months after the last dose of rituximab to avoid exposing the embryo.",
            "criterions": [
                {
                    "exact_snippets": [
                        "pregnant female partners"
                    ],
                    "criterion": "partner pregnancy",
                    "requirement_type": "status",
                    "expected_value": "pregnant"
                },
                {
                    "exact_snippets": [
                        "men must remain abstinent or use a condom"
                    ],
                    "criterion": "contraceptive method",
                    "requirement_type": "usage",
                    "expected_value": [
                        "abstinence",
                        "condom"
                    ]
                },
                {
                    "exact_snippets": [
                        "during the treatment period and for at least 6 months after the last dose of rituximab"
                    ],
                    "criterion": "contraceptive method",
                    "requirement_type": "duration",
                    "expected_value": "during the treatment period and for at least 6 months after the last dose of rituximab"
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": [
                        "Healthy volunteers allowed"
                    ],
                    "criterion": "healthy volunteers",
                    "requirement_type": "participation",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "Must have minimum age of 18 Years",
            "criterions": [
                {
                    "exact_snippets": [
                        "minimum age of 18 Years"
                    ],
                    "criterion": "age",
                    "requirement_type": "minimum",
                    "expected_value": {
                        "operator": ">=",
                        "value": 18
                    }
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "* Prior treatment toxicities have not resolved to ≤ Grade 2 according to NCI CTCAE Version 4.0 (except clinically insignificant toxicities such as alopecia).",
            "criterions": [
                {
                    "exact_snippets": [
                        "Prior treatment toxicities",
                        "have not resolved to ≤ Grade 2"
                    ],
                    "criterion": "prior treatment toxicities",
                    "requirement_type": "severity",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 2
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "clinically insignificant toxicities such as alopecia"
                    ],
                    "criterion": "clinically insignificant toxicities",
                    "requirement_type": "exclusion",
                    "expected_value": [
                        "alopecia"
                    ]
                }
            ]
        },
        {
            "line": "* Subjects receiving any other investigational agents.",
            "criterions": [
                {
                    "exact_snippets": [
                        "receiving any other investigational agents"
                    ],
                    "criterion": "investigational agents",
                    "requirement_type": "receiving",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "* Patients with active tumor lysis syndrome (TLS) either from laboratory or clinical changes.",
            "criterions": [
                {
                    "exact_snippets": [
                        "active tumor lysis syndrome (TLS)"
                    ],
                    "criterion": "tumor lysis syndrome",
                    "requirement_type": "activity",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "laboratory or clinical changes"
                    ],
                    "criterion": "tumor lysis syndrome",
                    "requirement_type": "detection method",
                    "expected_value": [
                        "laboratory",
                        "clinical"
                    ]
                }
            ]
        },
        {
            "line": "* Patients with active central nervous system (CNS) disease defined as symptomatic meningeal lymphoma or known CNS parenchymal lymphoma.",
            "criterions": [
                {
                    "exact_snippets": [
                        "active central nervous system (CNS) disease"
                    ],
                    "criterion": "central nervous system disease",
                    "requirement_type": "activity",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "symptomatic meningeal lymphoma"
                    ],
                    "criterion": "meningeal lymphoma",
                    "requirement_type": "symptom presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "known CNS parenchymal lymphoma"
                    ],
                    "criterion": "CNS parenchymal lymphoma",
                    "requirement_type": "knowledge",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "* History of severe allergic reactions attributed to compounds of similar chemical or biologic composition to rituximab or other agents used in this study.",
            "criterions": [
                {
                    "exact_snippets": [
                        "History of severe allergic reactions"
                    ],
                    "criterion": "allergic reactions",
                    "requirement_type": "severity",
                    "expected_value": "severe"
                },
                {
                    "exact_snippets": [
                        "attributed to compounds of similar chemical or biologic composition to rituximab"
                    ],
                    "criterion": "allergic reactions",
                    "requirement_type": "attribution",
                    "expected_value": "compounds of similar chemical or biologic composition to rituximab"
                },
                {
                    "exact_snippets": [
                        "attributed to",
                        "other agents used in this study"
                    ],
                    "criterion": "allergic reactions",
                    "requirement_type": "attribution",
                    "expected_value": "other agents used in this study"
                }
            ]
        },
        {
            "line": "* Subjects with uncontrolled intercurrent illness .",
            "criterions": [
                {
                    "exact_snippets": [
                        "uncontrolled intercurrent illness"
                    ],
                    "criterion": "intercurrent illness",
                    "requirement_type": "control",
                    "expected_value": false
                }
            ]
        },
        {
            "line": "* HIV-positive subjects on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Venetoclax. In addition, these subjects are at increased risk of lethal infections when treated with marrow suppressive therapy. Appropriate studies will be undertaken in subjects receiving combination antiretroviral therapy when indicated. HIV testing prior to enrollment is not required for screening but strongly encouraged for patients with no documented prior HIV assessment.",
            "criterions": [
                {
                    "exact_snippets": [
                        "HIV-positive subjects"
                    ],
                    "criterion": "HIV status",
                    "requirement_type": "presence",
                    "expected_value": "positive"
                },
                {
                    "exact_snippets": [
                        "combination antiretroviral therapy"
                    ],
                    "criterion": "antiretroviral therapy",
                    "requirement_type": "usage",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "HIV testing prior to enrollment is not required for screening"
                    ],
                    "criterion": "HIV testing",
                    "requirement_type": "requirement",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "strongly encouraged for patients with no documented prior HIV assessment"
                    ],
                    "criterion": "prior HIV assessment",
                    "requirement_type": "documentation",
                    "expected_value": false
                }
            ]
        },
        {
            "line": "* Presence of positive test results for hepatitis B virus (HBV), hepatitis B surface antigen (HBsAg), or hepatitis C (HCV) antibody.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Presence of positive test results for hepatitis B virus (HBV)"
                    ],
                    "criterion": "hepatitis B virus (HBV)",
                    "requirement_type": "test result",
                    "expected_value": "positive"
                },
                {
                    "exact_snippets": [
                        "Presence of positive test results for",
                        "hepatitis B surface antigen (HBsAg)"
                    ],
                    "criterion": "hepatitis B surface antigen (HBsAg)",
                    "requirement_type": "test result",
                    "expected_value": "positive"
                },
                {
                    "exact_snippets": [
                        "Presence of positive test results for",
                        "hepatitis C (HCV) antibody"
                    ],
                    "criterion": "hepatitis C (HCV) antibody",
                    "requirement_type": "test result",
                    "expected_value": "positive"
                }
            ]
        },
        {
            "line": "* Patients who are positive for HCV antibody must be negative for HCV by polymerase chain reaction (PCR) to be eligible for study participation",
            "criterions": [
                {
                    "exact_snippets": [
                        "positive for HCV antibody"
                    ],
                    "criterion": "HCV antibody",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "negative for HCV by polymerase chain reaction (PCR)"
                    ],
                    "criterion": "HCV by polymerase chain reaction (PCR)",
                    "requirement_type": "presence",
                    "expected_value": false
                }
            ]
        },
        {
            "line": "* Patients with occult or prior HBV infection (defined as positive total hepatitis B core antibody [HBcAb] and negative HBsAg) may be included if HBV DNA is undetectable. These patients must be willing to undergo monthly DNA testing.",
            "criterions": [
                {
                    "exact_snippets": [
                        "occult or prior HBV infection",
                        "positive total hepatitis B core antibody [HBcAb]",
                        "negative HBsAg"
                    ],
                    "criterion": "HBV infection",
                    "requirement_type": "status",
                    "expected_value": "occult or prior"
                },
                {
                    "exact_snippets": [
                        "positive total hepatitis B core antibody [HBcAb]"
                    ],
                    "criterion": "hepatitis B core antibody",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "negative HBsAg"
                    ],
                    "criterion": "hepatitis B surface antigen",
                    "requirement_type": "presence",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "HBV DNA is undetectable"
                    ],
                    "criterion": "HBV DNA",
                    "requirement_type": "detectability",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "willing to undergo monthly DNA testing"
                    ],
                    "criterion": "willingness for monthly DNA testing",
                    "requirement_type": "willingness",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "* Women who are pregnant or lactating",
            "criterions": [
                {
                    "exact_snippets": [
                        "Women who are pregnant"
                    ],
                    "criterion": "pregnancy",
                    "requirement_type": "status",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "lactating"
                    ],
                    "criterion": "lactation",
                    "requirement_type": "status",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "* Malabsorption syndrome or other condition that precludes enteral route of administration",
            "criterions": [
                {
                    "exact_snippets": [
                        "Malabsorption syndrome"
                    ],
                    "criterion": "malabsorption syndrome",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "other condition that precludes enteral route of administration"
                    ],
                    "criterion": "condition precluding enteral administration",
                    "requirement_type": "presence",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "* Chemotherapy or radiation within 3 weeks of the first scheduled study treatment.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Chemotherapy"
                    ],
                    "criterion": "chemotherapy",
                    "requirement_type": "recency",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 3
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "radiation"
                    ],
                    "criterion": "radiation",
                    "requirement_type": "recency",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 3
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Major surgery, other than diagnostic surgery, within 2 weeks.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Major surgery, other than diagnostic surgery, within 2 weeks"
                    ],
                    "criterion": "major surgery",
                    "requirement_type": "time since",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 2
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Medical condition requiring chronic use of high dose systemic corticosteroids (i.e., doses of prednisone higher than 10 mg/day or equivalent). Brief (<15 days) treatment with glucocorticoids (prednisone 100 mg by mouth daily, or equivalent) is acceptable.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Medical condition requiring chronic use of high dose systemic corticosteroids"
                    ],
                    "criterion": "chronic use of high dose systemic corticosteroids",
                    "requirement_type": "necessity",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "doses of prednisone higher than 10 mg/day or equivalent"
                    ],
                    "criterion": "prednisone dose",
                    "requirement_type": "quantity",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">",
                                "value": 10
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Known allergy to both xanthine oxidase inhibitors and rasburicase.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Known allergy to both xanthine oxidase inhibitors"
                    ],
                    "criterion": "xanthine oxidase inhibitors",
                    "requirement_type": "allergy",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "Known allergy to both",
                        "rasburicase"
                    ],
                    "criterion": "rasburicase",
                    "requirement_type": "allergy",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "* Use of warfarin is prohibited. Anticoagulation with low-molecular weight heparin (i.e. enoxaparin) or direct thrombin inhibitors is permitted.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Use of warfarin is prohibited"
                    ],
                    "criterion": "warfarin",
                    "requirement_type": "use",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "Anticoagulation with low-molecular weight heparin (i.e. enoxaparin)",
                        "is permitted"
                    ],
                    "criterion": "low-molecular weight heparin",
                    "requirement_type": "anticoagulation",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "Anticoagulation with",
                        "direct thrombin inhibitors is permitted"
                    ],
                    "criterion": "direct thrombin inhibitors",
                    "requirement_type": "anticoagulation",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "* Receipt of live-virus vaccines within 28 days prior to the initiation of study treatment or need for live-virus vaccines at any time during study treatment.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Receipt of live-virus vaccines within 28 days prior to the initiation of study treatment"
                    ],
                    "criterion": "live-virus vaccines",
                    "requirement_type": "receipt",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "need for live-virus vaccines at any time during study treatment"
                    ],
                    "criterion": "live-virus vaccines",
                    "requirement_type": "need",
                    "expected_value": false
                }
            ]
        },
        {
            "line": "* Concomitant medications that fall into the categories below could potentially lead to adverse reactions and should be considered with caution.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Concomitant medications"
                    ],
                    "criterion": "concomitant medications",
                    "requirement_type": "potential for adverse reactions",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "* Moderate/Weak CYP3A inducers such as efavirenz and oxcarbazepine",
            "criterions": [
                {
                    "exact_snippets": [
                        "Moderate/Weak CYP3A inducers"
                    ],
                    "criterion": "CYP3A inducers",
                    "requirement_type": "strength",
                    "expected_value": [
                        "Moderate",
                        "Weak"
                    ]
                },
                {
                    "exact_snippets": [
                        "efavirenz"
                    ],
                    "criterion": "CYP3A inducer",
                    "requirement_type": "example",
                    "expected_value": "efavirenz"
                },
                {
                    "exact_snippets": [
                        "oxcarbazepine"
                    ],
                    "criterion": "CYP3A inducer",
                    "requirement_type": "example",
                    "expected_value": "oxcarbazepine"
                }
            ]
        },
        {
            "line": "* CYP2C8 substrates such as thiazolidinediones (glitazones) and select statins (because of expected inhibition of the metabolism of CYP2C8 substrates) by venetoclax",
            "criterions": [
                {
                    "exact_snippets": [
                        "CYP2C8 substrates such as thiazolidinediones (glitazones) and select statins"
                    ],
                    "criterion": "CYP2C8 substrates",
                    "requirement_type": "concomitant medication",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "expected inhibition of the metabolism of CYP2C8 substrates",
                        "by venetoclax"
                    ],
                    "criterion": "CYP2C8 substrates metabolism",
                    "requirement_type": "inhibition",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "* CYP2C9 substrates such as tolbutamide (because of expected inhibition of the metabolism of CYP2C9 substrates by venetoclax. It is recommended to exclude CYP2C9 substrates with a narrow therapeutic index such as phenytoin.",
            "criterions": [
                {
                    "exact_snippets": [
                        "CYP2C9 substrates"
                    ],
                    "criterion": "CYP2C9 substrates",
                    "requirement_type": "exclusion",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "CYP2C9 substrates",
                        "narrow therapeutic index"
                    ],
                    "criterion": "CYP2C9 substrates",
                    "requirement_type": "therapeutic index",
                    "expected_value": "narrow"
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "line": "* For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:",
            "criterions": [
                {
                    "exact_snippets": [
                        "For men: agreement to remain abstinent (refrain from heterosexual intercourse)"
                    ],
                    "criterion": "abstinence",
                    "requirement_type": "agreement",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures"
                    ],
                    "criterion": "contraceptive measures",
                    "requirement_type": "agreement",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "For men: agreement to refrain from donating sperm"
                    ],
                    "criterion": "sperm donation",
                    "requirement_type": "agreement",
                    "expected_value": false
                }
            ]
        }
    ],
    "failed_exclusion": [
        {
            "line": "* Less than 2-year disease free from another primary malignancy (other than squamous or basal cell carcinoma of the skin, \"in-situ\" carcinoma of the cervix or breast, superficial bladder carcinoma, or previously treated localized prostate cancer with normal prostate specific antigen (PSA) levels). Patients who have had completed all anti-cancer treatment for another primary malignancy more than 2 years prior to screening are eligible if they are not considered to have a \"currently active\" malignancy based on having less than a 30% risk of relapse.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Less than 2-year disease free from another primary malignancy"
                    ],
                    "criterion": "disease-free interval from another primary malignancy",
                    "requirement_type": "duration",
                    "expected_value": {
                        "operator": "<",
                        "value": 2
                    }
                },
                {
                    "exact_snippets": [
                        "squamous or basal cell carcinoma of the skin"
                    ],
                    "criterion": "squamous or basal cell carcinoma of the skin",
                    "requirement_type": "presence",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "\"in-situ\" carcinoma of the cervix"
                    ],
                    "criterion": "\"in-situ\" carcinoma of the cervix",
                    "requirement_type": "presence",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "\"in-situ\" carcinoma of the breast"
                    ],
                    "criterion": "\"in-situ\" carcinoma of the breast",
                    "requirement_type": "presence",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "superficial bladder carcinoma"
                    ],
                    "criterion": "superficial bladder carcinoma",
                    "requirement_type": "presence",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "previously treated localized prostate cancer with normal prostate specific antigen (PSA) levels"
                    ],
                    "criterion": "previously treated localized prostate cancer with normal PSA levels",
                    "requirement_type": "presence",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "completed all anti-cancer treatment for another primary malignancy more than 2 years prior to screening"
                    ],
                    "criterion": "completion of all anti-cancer treatment for another primary malignancy",
                    "requirement_type": "time since completion",
                    "expected_value": {
                        "operator": ">",
                        "value": 2
                    }
                },
                {
                    "exact_snippets": [
                        "not considered to have a \"currently active\" malignancy based on having less than a 30% risk of relapse"
                    ],
                    "criterion": "risk of relapse",
                    "requirement_type": "probability",
                    "expected_value": {
                        "operator": "<",
                        "value": 30
                    }
                }
            ]
        },
        {
            "line": "* The following concomitant medications are not allowed from 7 days prior to the first dose of study drug and during venetoclax administration: Strong CYP3A4 inhibitors including but not limited to fluconazole, ketoconazole, and clarithromycin or strong CYP3A4 inducers included but not limited to rifampin, carbamazepine.",
            "criterions": [
                {
                    "exact_snippets": [
                        "concomitant medications are not allowed",
                        "Strong CYP3A4 inhibitors"
                    ],
                    "criterion": "concomitant medications",
                    "requirement_type": "allowance",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "concomitant medications are not allowed",
                        "Strong CYP3A4 inducers"
                    ],
                    "criterion": "concomitant medications",
                    "requirement_type": "allowance",
                    "expected_value": false
                }
            ]
        }
    ],
    "failed_miscellaneous": []
}