{
    "info": {
        "nct_id": "NCT02795182",
        "official_title": "A Phase 1b, Open Label, Multiple Dose, Dose Escalation and Expansion Study to Assess Safety, Tolerability and Antitumor Activities of the Combination of BGB-3111 With BGB-A317 in Subjects With B-Cell Lymphoid Malignancies",
        "inclusion_criteria": "Healthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "",
        "miscellaneous_criteria": "Key Inclusion Criteria\n\nParticipants may be entered in the study only if they meet all of the following criteria:\n\n1. Dose escalation for Dose Levels 1, 2, and 3: participants with relapsed or refractory World Health Organization (WHO) classification-defined B-lymphoid malignancy following at least 1 line of therapy, with no therapy of higher priority available, including chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), follicular lymphoma (FL), human cultured lymphoblast (HCL), Marginal zone lymphoma (MZL), non-germinal center B-cell (GCB) DLBCL, GCB DLBCL, transformed FL, and Richter's transformation (NOTE: participants with WM are excluded from enrollment as of Amendment 3).\n2. Dose expansion for Cohorts 1 to 4: participants with either of the following relapsed or refractory WHO-classified lymphoid malignancies who have received at least 1 prior line of standard therapy: a. Cohort 1: GCB DLBCL, with cell of origin defined by either immunohistochemistry or gene expression profiling. b. Cohort 2: non-GCB DLBCL, with cell of origin defined by either immunohistochemistry or gene expression profiling. participants who have transformed to DLBCL from another histology may be enrolled into Cohort 3. c. Cohort 3: Transformed lymphoid malignancy, including but not limited to: i. Large cell transformation of chronic lymphocytic leukemia (Richter's transformation). ii. Large cell transformation of other WHO-classified indolent non-Hodgkin's lymphoma, including FL, or MZL. d. Cohort 4: Histologically confirmed primary central nervous system lymphoma (PCNSL) or secondary central nervous system lymphoma (SCNSL) of breast or testicular origin: i. Must be able to tolerate lumbar puncture and/or Ommaya taps. ii. Must have received at least 1 prior central nervous system (CNS)-directed therapy. iii. Presence of brain parenchymal and/or leptomeningeal disease.\n3. Aged ≥ 18 years, able and willing to provide written informed consent and to comply with the study protocol.\n4. Measurable disease for non-Hodgkin lymphoma defined as ≥ 1 nodal lesion that is > 15 mm in the longest diameter and can be accurately measured in at least 2 dimensions with computed tomography (CT) scan, or ≥ 1 extra-nodal lesion that is > 10 mm in the longest diameter and can be accurately measured in at least 2 dimensions with CT scan, except for PCNSL or SCNSL.\n5. Participants with an accessible tumor lesion must agree to a tumor biopsy at screening and another before the drug administration on Cycle 1 Day 8, ideally taken from the same tumor lesion, for biomarker analysis (up to first 12 qualified participants), except for PCNSL. Additionally, participants with DLBCL must have archival tumor tissue or agree to a tumor biopsy for confirmation of the DLBCL subtype.\n6. Laboratory parameters as specified below: a. Hematologic: Platelet count ≥ 50 × 109/L; absolute neutrophil count ≥ 1.0 × 109 cells/L; participants with neutrophils < 1.0 × 109/L unless cytopenias are a direct result of active leukemia or lymphoma, in which case platelet count ≥ 35 × 109/L, absolute neutrophil count ≥ 0.75 × 109/L are allowed. (Note: Platelet transfusion administered ≤ 7 days of screening to raise pre-treatment platelet count to ≥ 35 x 109/L is prohibited.) b. Hepatic: Total bilirubin ≤ 1.5 the upper limit of normal (ULN) or ≤ 2.0 × ULN for participants with Gilbert syndrome, aspartate transaminase (AST), and alanine aminotransaminase (ALT) ≤ 3 × ULN. c. Renal: Creatinine clearance ≥ 30 mL/min (as estimated by the Cockcroft-Gault equation or as measured by nuclear medicine scan or 24-hour urine collection). participants requiring hemodialysis will be excluded.\n7. Anticipated survival of at least 4 months.\n8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.\n9. Female participants of childbearing potential and nonsterile males must practice at least 1 of the following methods of birth control with partner(s) throughout the study and for ≥ 3 months after discontinuing study drug: total abstinence from sexual intercourse, double-barrier contraception, intrauterine device or hormonal contraceptive initiated at least 3 months prior to first dose of study drug.\n10. Male participants must not donate sperm from initial study drug administration until 180 days after drug discontinuation.\n\nKey Exclusion Criteria\n\nParticipants will not be entered in the study for any of the following reasons:\n\n1. Known, active, CNS lymphoma or leukemia, except for Cohorts 4.\n2. Diagnosis with Waldenstrom's macroglobulinemia (WM).\n3. For PCNSL and SCNSL (Cohorts 4): a. Require corticosteroid therapy > 16 mg dexamethasone daily or equivalent. b. Corticosteroid therapy ≤ 16 mg dexamethasone daily or equivalent at study entry from which, in the Investigator's opinion, it is expected that the participant cannot be tapered off after the first 4 weeks of study treatment. c. Intraocular PCNSL without evidence of brain disease. d. SCNSL actively receiving treatment for extra-CNS disease. e. PCNSL actively receiving concomitant local or systemic therapy for CNS disease.\n4. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.\n5. History of stroke or cerebral hemorrhage within 6 months of enrollment.\n6. History of significant cardiovascular disease, defined as: a. Congestive heart failure greater than New York Heart Association (NYHA) class II according to the NYHA functional classification. b. Unstable angina or myocardial infarction with 6 months of enrollment. c. Serious cardiac arrhythmia or clinically significant ECG abnormality: corrected QT wave (QTcF) > 480 msec based on the Fridericia's formula or other ECG abnormalities including second-degree atrioventricular block type II, third-degree atrioventricular block. Participants who have a pacemaker will be allowed on study despite ECG abnormalities or the inability to calculate the QTc.\n7. Severe or debilitating pulmonary disease (dyspnea at rest, significant shortness of breath, congestive obstructive pulmonary disease).\n8. History of severe allergic or anaphylactic reactions to monoclonal antibody therapy.\n9. Prior Bruton's tyrosine kinase (BTK) inhibitor or anti-PD-1/anti-PD-L1 treatment.\n10. Any illness or condition that in the opinion of the investigator may affect safety of treatment or evaluation of any study endpoint.\n11. Active autoimmune diseases or history of severe autoimmune diseases; these include but are not limited to a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis systemic lupus erythematosus, rheumatoid arthritis, connective tissue diseases, scleroderma, inflammatory bowel disease, Crohn's disease, ulcerative colitis, autoimmune hepatitis, toxic epidermal necrolysis, Stevens-Johnson syndrome, or clinically manifest antiphospholipid syndrome. Note: Participants are permitted to enroll if they have vitiligo, eczema, type I diabetes mellitus, or endocrine deficiencies, including thyroiditis managed with replacement hormones including physiologic doses of corticosteroids. Participants with Sjögren's syndrome and psoriasis controlled with topical medication and participants with positive serology, such as antinuclear antibodies or antithyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible.\n12. A condition requiring systemic treatment with either corticosteroids (> 20 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration, except for PCNSL and SCNSL. Note: adrenal replacement doses ≤ 20 mg daily prednisone or equivalents are permitted in the absence of active autoimmune disease; Participants are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption).\n13. History of interstitial lung disease or noninfectious pneumonitis, except for those induced by radiation therapy.\n14. Requirement for medications which strong cytochrome P450 (CYP)3A inhibitors or inducers.\n15. Vaccination with a live vaccine within 28 days of the initiation of treatment.\n16. A candidate for hematopoietic stem cell transplantation. Participants are excluded if they had received an allogeneic stem cell transplantation within 6 months or have active graft-versus-host-disease requiring ongoing immunosuppression.\n17. Participated in any investigational drug study within 28 days or not recovered from toxicity of any prior chemotherapy to Grade ≤ 1.\n18. History of other active malignancies within 2 years of study entry, with the exception of adequately treated in-situ carcinoma of cervix; localized basal cell or squamous cell carcinoma of skin; or previous malignancy confined and treated locally (surgery or other modality) with curative intent.\n19. Major surgery in the past 4 weeks prior to the first day of screening.\n20. Active and symptomatic fungal, bacterial, and/or viral infection; human T-cell lymphotropic virus type 1 seropositive status.\n21. Human immunodeficiency virus (HIV) infection, or active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] detected. • Hepatitis B/C serologic markers and viral load will be tested at screening. The hepatitis B testing includes HBsAg, HBcAb, and HBsAb as well as hepatitis B virus (HBV) DNA by Polymerase chain reaction (PCR) if the participant is negative for HBsAg but HBcAb positive (regardless of HBsAb status). The hepatitis C testing includes Hepatitis C virus (HCV) antibody as well as HCV RNA by PCR if the Participant is HCV antibody positive. Participants with positive HBsAg and/or detectable level of HBV DNA or detectable level of HCV RNA (≥ 15 IU/mL) are not eligible. Participants negative for HBsAg, HBcAb positive, and HBV DNA negative must undergo monthly HBV DNA screening by PCR. Participants positive for HCV antibody but negative for HCV RNA (defined as < 15 IU) must undergo monthly HCV RNA screening.\n22. Inability to comply with study procedures.\n23. Pregnant or nursing women.\n24. Men or women of childbearing potential who refuse to use an adequate measure of contraception, unless they have past medical history of surgical sterilization.\n25. Currently taking or plan to take CNS penetrant therapy such as thiotepa, cytarabine, or partially CNS penetrant agents known to be active in lymphoid tumors, such as rituximab.\n26. Has taken or plans to take any chemotherapy, immunotherapy (eg, interleukin, interferon, thymoxin), or any investigational therapies to treat leukemia or lymphoma within 28 days or 5 half-lives (whichever is shorter) of the first study drug administration, including CNS penetrating agents.\n\nNOTE: Other protocol defined Inclusion/Exclusion criteria may apply."
    },
    "inclusion_lines": [
        {
            "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": [],
    "miscellaneous_lines": [
        {
            "line": "1. Dose escalation for Dose Levels 1, 2, and 3: participants with relapsed or refractory World Health Organization (WHO) classification-defined B-lymphoid malignancy following at least 1 line of therapy, with no therapy of higher priority available, including chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), follicular lymphoma (FL), human cultured lymphoblast (HCL), Marginal zone lymphoma (MZL), non-germinal center B-cell (GCB) DLBCL, GCB DLBCL, transformed FL, and Richter's transformation (NOTE: participants with WM are excluded from enrollment as of Amendment 3).",
            "criterions": [
                {
                    "exact_snippets": "relapsed or refractory World Health Organization (WHO) classification-defined B-lymphoid malignancy",
                    "criterion": "B-lymphoid malignancy",
                    "requirements": [
                        {
                            "requirement_type": "classification",
                            "expected_value": "relapsed or refractory WHO classification-defined"
                        }
                    ]
                },
                {
                    "exact_snippets": "following at least 1 line of therapy",
                    "criterion": "previous therapy",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "line of therapy"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "no therapy of higher priority available",
                    "criterion": "availability of higher priority therapy",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)",
                    "criterion": "chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "mantle cell lymphoma (MCL)",
                    "criterion": "mantle cell lymphoma (MCL)",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "follicular lymphoma (FL)",
                    "criterion": "follicular lymphoma (FL)",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "human cultured lymphoblast (HCL)",
                    "criterion": "human cultured lymphoblast (HCL)",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Marginal zone lymphoma (MZL)",
                    "criterion": "Marginal zone lymphoma (MZL)",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "non-germinal center B-cell (GCB) DLBCL",
                    "criterion": "non-germinal center B-cell (GCB) DLBCL",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "GCB DLBCL",
                    "criterion": "GCB DLBCL",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "transformed FL",
                    "criterion": "transformed FL",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Richter's transformation",
                    "criterion": "Richter's transformation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "participants with WM are excluded from enrollment as of Amendment 3",
                    "criterion": "Waldenström macroglobulinemia (WM)",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Aged ≥ 18 years, able and willing to provide written informed consent and to comply with the study protocol.",
            "criterions": [
                {
                    "exact_snippets": "Aged ≥ 18 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "able and willing to provide written informed consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "able and willing ... to comply with the study protocol",
                    "criterion": "compliance with study protocol",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Measurable disease for non-Hodgkin lymphoma defined as ≥ 1 nodal lesion that is > 15 mm in the longest diameter and can be accurately measured in at least 2 dimensions with computed tomography (CT) scan, or ≥ 1 extra-nodal lesion that is > 10 mm in the longest diameter and can be accurately measured in at least 2 dimensions with CT scan, except for PCNSL or SCNSL.",
            "criterions": [
                {
                    "exact_snippets": "Measurable disease for non-Hodgkin lymphoma",
                    "criterion": "measurable disease for non-Hodgkin lymphoma",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "≥ 1 nodal lesion that is > 15 mm in the longest diameter",
                    "criterion": "nodal lesion",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "lesion"
                            }
                        },
                        {
                            "requirement_type": "size",
                            "expected_value": {
                                "operator": ">",
                                "value": 15,
                                "unit": "mm"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "can be accurately measured in at least 2 dimensions with computed tomography (CT) scan",
                    "criterion": "nodal lesion measurement",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": "computed tomography (CT) scan"
                        },
                        {
                            "requirement_type": "dimensions",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "dimensions"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "≥ 1 extra-nodal lesion that is > 10 mm in the longest diameter",
                    "criterion": "extra-nodal lesion",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "lesion"
                            }
                        },
                        {
                            "requirement_type": "size",
                            "expected_value": {
                                "operator": ">",
                                "value": 10,
                                "unit": "mm"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "can be accurately measured in at least 2 dimensions with CT scan",
                    "criterion": "extra-nodal lesion measurement",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": "CT scan"
                        },
                        {
                            "requirement_type": "dimensions",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "dimensions"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "except for PCNSL or SCNSL",
                    "criterion": "PCNSL or SCNSL",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Participants with an accessible tumor lesion must agree to a tumor biopsy at screening and another before the drug administration on Cycle 1 Day 8, ideally taken from the same tumor lesion, for biomarker analysis (up to first 12 qualified participants), except for PCNSL. Additionally, participants with DLBCL must have archival tumor tissue or agree to a tumor biopsy for confirmation of the DLBCL subtype.",
            "criterions": [
                {
                    "exact_snippets": "Participants with an accessible tumor lesion must agree to a tumor biopsy at screening",
                    "criterion": "tumor biopsy at screening",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "another before the drug administration on Cycle 1 Day 8",
                    "criterion": "tumor biopsy before drug administration",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "before drug administration on Cycle 1 Day 8"
                        }
                    ]
                },
                {
                    "exact_snippets": "ideally taken from the same tumor lesion",
                    "criterion": "tumor biopsy location consistency",
                    "requirements": [
                        {
                            "requirement_type": "consistency",
                            "expected_value": "same tumor lesion"
                        }
                    ]
                },
                {
                    "exact_snippets": "for biomarker analysis (up to first 12 qualified participants)",
                    "criterion": "biomarker analysis",
                    "requirements": [
                        {
                            "requirement_type": "participant limit",
                            "expected_value": {
                                "operator": "<=",
                                "value": 12,
                                "unit": "participants"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "except for PCNSL",
                    "criterion": "PCNSL exclusion",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "participants with DLBCL must have archival tumor tissue or agree to a tumor biopsy for confirmation of the DLBCL subtype",
                    "criterion": "DLBCL subtype confirmation",
                    "requirements": [
                        {
                            "requirement_type": "archival tumor tissue",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "agreement for tumor biopsy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Laboratory parameters as specified below: a. Hematologic: Platelet count ≥ 50 × 109/L; absolute neutrophil count ≥ 1.0 × 109 cells/L; participants with neutrophils < 1.0 × 109/L unless cytopenias are a direct result of active leukemia or lymphoma, in which case platelet count ≥ 35 × 109/L, absolute neutrophil count ≥ 0.75 × 109/L are allowed. (Note: Platelet transfusion administered ≤ 7 days of screening to raise pre-treatment platelet count to ≥ 35 x 109/L is prohibited.) b. Hepatic: Total bilirubin ≤ 1.5 the upper limit of normal (ULN) or ≤ 2.0 × ULN for participants with Gilbert syndrome, aspartate transaminase (AST), and alanine aminotransaminase (ALT) ≤ 3 × ULN. c. Renal: Creatinine clearance ≥ 30 mL/min (as estimated by the Cockcroft-Gault equation or as measured by nuclear medicine scan or 24-hour urine collection). participants requiring hemodialysis will be excluded.",
            "criterions": [
                {
                    "exact_snippets": "Platelet count ≥ 50 × 109/L",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 50,
                                "unit": "× 109/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "absolute neutrophil count ≥ 1.0 × 109 cells/L",
                    "criterion": "absolute neutrophil count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.0,
                                "unit": "× 109 cells/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "participants with neutrophils < 1.0 × 109/L unless cytopenias are a direct result of active leukemia or lymphoma, in which case platelet count ≥ 35 × 109/L, absolute neutrophil count ≥ 0.75 × 109/L are allowed",
                    "criterion": "neutrophils",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<",
                                "value": 1.0,
                                "unit": "× 109/L"
                            }
                        },
                        {
                            "requirement_type": "condition",
                            "expected_value": "cytopenias are a direct result of active leukemia or lymphoma"
                        }
                    ]
                },
                {
                    "exact_snippets": "platelet count ≥ 35 × 109/L",
                    "criterion": "platelet count (with active leukemia or lymphoma)",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 35,
                                "unit": "× 109/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "absolute neutrophil count ≥ 0.75 × 109/L",
                    "criterion": "absolute neutrophil count (with active leukemia or lymphoma)",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 0.75,
                                "unit": "× 109/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Platelet transfusion administered ≤ 7 days of screening to raise pre-treatment platelet count to ≥ 35 x 109/L is prohibited",
                    "criterion": "platelet transfusion",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "≤ 7 days of screening"
                        },
                        {
                            "requirement_type": "purpose",
                            "expected_value": "raise pre-treatment platelet count to ≥ 35 x 109/L"
                        },
                        {
                            "requirement_type": "allowance",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Total bilirubin ≤ 1.5 the upper limit of normal (ULN) or ≤ 2.0 × ULN for participants with Gilbert syndrome",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "ULN"
                            }
                        },
                        {
                            "requirement_type": "quantity (Gilbert syndrome)",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.0,
                                "unit": "× ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "aspartate transaminase (AST), and alanine aminotransaminase (ALT) ≤ 3 × ULN",
                    "criterion": "AST and ALT",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "× ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Creatinine clearance ≥ 30 mL/min (as estimated by the Cockcroft-Gault equation or as measured by nuclear medicine scan or 24-hour urine collection)",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 30,
                                "unit": "mL/min"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "participants requiring hemodialysis will be excluded",
                    "criterion": "hemodialysis requirement",
                    "requirements": [
                        {
                            "requirement_type": "allowance",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Anticipated survival of at least 4 months.",
            "criterions": [
                {
                    "exact_snippets": "Anticipated survival of at least 4 months.",
                    "criterion": "anticipated survival",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 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": "9. Female participants of childbearing potential and nonsterile males must practice at least 1 of the following methods of birth control with partner(s) throughout the study and for ≥ 3 months after discontinuing study drug: total abstinence from sexual intercourse, double-barrier contraception, intrauterine device or hormonal contraceptive initiated at least 3 months prior to first dose of study drug.",
            "criterions": [
                {
                    "exact_snippets": "Female participants of childbearing potential",
                    "criterion": "female participants of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "nonsterile males",
                    "criterion": "nonsterile males",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "must practice at least 1 of the following methods of birth control with partner(s) throughout the study and for ≥ 3 months after discontinuing study drug",
                    "criterion": "birth control practice",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "throughout the study and for ≥ 3 months after discontinuing study drug"
                        }
                    ]
                },
                {
                    "exact_snippets": "total abstinence from sexual intercourse",
                    "criterion": "birth control method",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": "total abstinence from sexual intercourse"
                        }
                    ]
                },
                {
                    "exact_snippets": "double-barrier contraception",
                    "criterion": "birth control method",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": "double-barrier contraception"
                        }
                    ]
                },
                {
                    "exact_snippets": "intrauterine device",
                    "criterion": "birth control method",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": "intrauterine device"
                        }
                    ]
                },
                {
                    "exact_snippets": "hormonal contraceptive initiated at least 3 months prior to first dose of study drug",
                    "criterion": "birth control method",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": "hormonal contraceptive"
                        },
                        {
                            "requirement_type": "initiation time",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "months prior to first dose of study drug"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Male participants must not donate sperm from initial study drug administration until 180 days after drug discontinuation.",
            "criterions": [
                {
                    "exact_snippets": "Male participants must not donate sperm",
                    "criterion": "sperm donation",
                    "requirements": [
                        {
                            "requirement_type": "restriction",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "from initial study drug administration until 180 days after drug discontinuation",
                    "criterion": "time period for sperm donation restriction",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "from initial study drug administration until 180 days after drug discontinuation"
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Known, active, CNS lymphoma or leukemia, except for Cohorts 4.",
            "criterions": [
                {
                    "exact_snippets": "Known, active, CNS lymphoma",
                    "criterion": "CNS lymphoma",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Known, active, ... leukemia",
                    "criterion": "leukemia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Diagnosis with Waldenstrom's macroglobulinemia (WM).",
            "criterions": [
                {
                    "exact_snippets": "Diagnosis with Waldenstrom's macroglobulinemia (WM)",
                    "criterion": "Waldenstrom's macroglobulinemia diagnosis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. For PCNSL and SCNSL (Cohorts 4): a. Require corticosteroid therapy > 16 mg dexamethasone daily or equivalent. b. Corticosteroid therapy ≤ 16 mg dexamethasone daily or equivalent at study entry from which, in the Investigator's opinion, it is expected that the participant cannot be tapered off after the first 4 weeks of study treatment. c. Intraocular PCNSL without evidence of brain disease. d. SCNSL actively receiving treatment for extra-CNS disease. e. PCNSL actively receiving concomitant local or systemic therapy for CNS disease.",
            "criterions": [
                {
                    "exact_snippets": "PCNSL and SCNSL (Cohorts 4)",
                    "criterion": "PCNSL and SCNSL",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Require corticosteroid therapy > 16 mg dexamethasone daily or equivalent",
                    "criterion": "corticosteroid therapy",
                    "requirements": [
                        {
                            "requirement_type": "dosage",
                            "expected_value": {
                                "operator": ">",
                                "value": 16,
                                "unit": "mg dexamethasone daily or equivalent"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Corticosteroid therapy ≤ 16 mg dexamethasone daily or equivalent at study entry",
                    "criterion": "corticosteroid therapy",
                    "requirements": [
                        {
                            "requirement_type": "dosage",
                            "expected_value": {
                                "operator": "<=",
                                "value": 16,
                                "unit": "mg dexamethasone daily or equivalent"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "it is expected that the participant cannot be tapered off after the first 4 weeks of study treatment",
                    "criterion": "corticosteroid therapy tapering",
                    "requirements": [
                        {
                            "requirement_type": "expectation",
                            "expected_value": "cannot be tapered off after the first 4 weeks of study treatment"
                        }
                    ]
                },
                {
                    "exact_snippets": "Intraocular PCNSL without evidence of brain disease",
                    "criterion": "Intraocular PCNSL",
                    "requirements": [
                        {
                            "requirement_type": "brain disease evidence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "SCNSL actively receiving treatment for extra-CNS disease",
                    "criterion": "SCNSL treatment",
                    "requirements": [
                        {
                            "requirement_type": "extra-CNS disease treatment",
                            "expected_value": "actively receiving"
                        }
                    ]
                },
                {
                    "exact_snippets": "PCNSL actively receiving concomitant local or systemic therapy for CNS disease",
                    "criterion": "PCNSL therapy",
                    "requirements": [
                        {
                            "requirement_type": "CNS disease therapy",
                            "expected_value": "actively receiving concomitant local or systemic"
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled autoimmune hemolytic anemia",
                    "criterion": "autoimmune hemolytic anemia",
                    "requirements": [
                        {
                            "requirement_type": "control status",
                            "expected_value": "uncontrolled"
                        }
                    ]
                },
                {
                    "exact_snippets": "idiopathic thrombocytopenia purpura",
                    "criterion": "idiopathic thrombocytopenia purpura",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. History of stroke or cerebral hemorrhage within 6 months of enrollment.",
            "criterions": [
                {
                    "exact_snippets": "History of stroke",
                    "criterion": "stroke",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 6,
                                        "unit": "months"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "cerebral hemorrhage",
                    "criterion": "cerebral hemorrhage",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 6,
                                        "unit": "months"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Severe or debilitating pulmonary disease (dyspnea at rest, significant shortness of breath, congestive obstructive pulmonary disease).",
            "criterions": [
                {
                    "exact_snippets": "Severe or debilitating pulmonary disease",
                    "criterion": "pulmonary disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe or debilitating"
                        }
                    ]
                },
                {
                    "exact_snippets": "dyspnea at rest",
                    "criterion": "dyspnea",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "condition",
                            "expected_value": "at rest"
                        }
                    ]
                },
                {
                    "exact_snippets": "significant shortness of breath",
                    "criterion": "shortness of breath",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "significant"
                        }
                    ]
                },
                {
                    "exact_snippets": "congestive obstructive pulmonary disease",
                    "criterion": "congestive obstructive pulmonary disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. History of severe allergic or anaphylactic reactions to monoclonal antibody therapy.",
            "criterions": [
                {
                    "exact_snippets": "History of severe allergic or anaphylactic reactions to monoclonal antibody therapy.",
                    "criterion": "allergic or anaphylactic reactions to monoclonal antibody therapy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        },
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Prior Bruton's tyrosine kinase (BTK) inhibitor or anti-PD-1/anti-PD-L1 treatment.",
            "criterions": [
                {
                    "exact_snippets": "Prior Bruton's tyrosine kinase (BTK) inhibitor",
                    "criterion": "Bruton's tyrosine kinase (BTK) inhibitor treatment",
                    "requirements": [
                        {
                            "requirement_type": "prior treatment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "anti-PD-1/anti-PD-L1 treatment",
                    "criterion": "anti-PD-1/anti-PD-L1 treatment",
                    "requirements": [
                        {
                            "requirement_type": "prior treatment",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Any illness or condition that in the opinion of the investigator may affect safety of treatment or evaluation of any study endpoint.",
            "criterions": [
                {
                    "exact_snippets": "Any illness or condition ... may affect safety of treatment",
                    "criterion": "illness or condition affecting safety of treatment",
                    "requirements": [
                        {
                            "requirement_type": "opinion of the investigator",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Any illness or condition ... may affect ... evaluation of any study endpoint",
                    "criterion": "illness or condition affecting evaluation of study endpoint",
                    "requirements": [
                        {
                            "requirement_type": "opinion of the investigator",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Active autoimmune diseases or history of severe autoimmune diseases; these include but are not limited to a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis systemic lupus erythematosus, rheumatoid arthritis, connective tissue diseases, scleroderma, inflammatory bowel disease, Crohn's disease, ulcerative colitis, autoimmune hepatitis, toxic epidermal necrolysis, Stevens-Johnson syndrome, or clinically manifest antiphospholipid syndrome. Note: Participants are permitted to enroll if they have vitiligo, eczema, type I diabetes mellitus, or endocrine deficiencies, including thyroiditis managed with replacement hormones including physiologic doses of corticosteroids. Participants with Sjögren's syndrome and psoriasis controlled with topical medication and participants with positive serology, such as antinuclear antibodies or antithyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible.",
            "criterions": [
                {
                    "exact_snippets": "Active autoimmune diseases or history of severe autoimmune diseases",
                    "criterion": "autoimmune diseases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "history of immune related neurologic disease",
                    "criterion": "immune related neurologic disease",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "multiple sclerosis",
                    "criterion": "multiple sclerosis",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "autoimmune (demyelinating) neuropathy",
                    "criterion": "autoimmune (demyelinating) neuropathy",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Guillain-Barre syndrome",
                    "criterion": "Guillain-Barre syndrome",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "myasthenia gravis",
                    "criterion": "myasthenia gravis",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "systemic lupus erythematosus",
                    "criterion": "systemic lupus erythematosus",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "rheumatoid arthritis",
                    "criterion": "rheumatoid arthritis",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "connective tissue diseases",
                    "criterion": "connective tissue diseases",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "scleroderma",
                    "criterion": "scleroderma",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "inflammatory bowel disease",
                    "criterion": "inflammatory bowel disease",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Crohn's disease",
                    "criterion": "Crohn's disease",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "ulcerative colitis",
                    "criterion": "ulcerative colitis",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "autoimmune hepatitis",
                    "criterion": "autoimmune hepatitis",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "toxic epidermal necrolysis",
                    "criterion": "toxic epidermal necrolysis",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Stevens-Johnson syndrome",
                    "criterion": "Stevens-Johnson syndrome",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "clinically manifest antiphospholipid syndrome",
                    "criterion": "clinically manifest antiphospholipid syndrome",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "vitiligo",
                    "criterion": "vitiligo",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "eczema",
                    "criterion": "eczema",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "type I diabetes mellitus",
                    "criterion": "type I diabetes mellitus",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "endocrine deficiencies, including thyroiditis managed with replacement hormones including physiologic doses of corticosteroids",
                    "criterion": "endocrine deficiencies",
                    "requirements": [
                        {
                            "requirement_type": "management",
                            "expected_value": "replacement hormones including physiologic doses of corticosteroids"
                        }
                    ]
                },
                {
                    "exact_snippets": "Sjögren's syndrome",
                    "criterion": "Sjögren's syndrome",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "topical medication"
                        }
                    ]
                },
                {
                    "exact_snippets": "psoriasis controlled with topical medication",
                    "criterion": "psoriasis",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "topical medication"
                        }
                    ]
                },
                {
                    "exact_snippets": "positive serology, such as antinuclear antibodies or antithyroid antibodies",
                    "criterion": "positive serology",
                    "requirements": [
                        {
                            "requirement_type": "evaluation",
                            "expected_value": "presence of target organ involvement and potential need for systemic treatment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. A condition requiring systemic treatment with either corticosteroids (> 20 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration, except for PCNSL and SCNSL. Note: adrenal replacement doses ≤ 20 mg daily prednisone or equivalents are permitted in the absence of active autoimmune disease; Participants are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption).",
            "criterions": [
                {
                    "exact_snippets": "A condition requiring systemic treatment with either corticosteroids (> 20 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration",
                    "criterion": "systemic treatment with corticosteroids or immunosuppressive medications",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "adrenal replacement doses ≤ 20 mg daily prednisone or equivalents are permitted",
                    "criterion": "adrenal replacement doses",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 20,
                                "unit": "mg daily prednisone or equivalents"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Participants are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption)",
                    "criterion": "use of topical, ocular, intra-articular, intranasal, and inhalational corticosteroids",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. History of interstitial lung disease or noninfectious pneumonitis, except for those induced by radiation therapy.",
            "criterions": [
                {
                    "exact_snippets": "History of interstitial lung disease",
                    "criterion": "interstitial lung disease",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "History of ... noninfectious pneumonitis",
                    "criterion": "noninfectious pneumonitis",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "14. Requirement for medications which strong cytochrome P450 (CYP)3A inhibitors or inducers.",
            "criterions": [
                {
                    "exact_snippets": "Requirement for medications which strong cytochrome P450 (CYP)3A inhibitors or inducers.",
                    "criterion": "medications",
                    "requirements": [
                        {
                            "requirement_type": "interaction with cytochrome P450 (CYP)3A",
                            "expected_value": [
                                "strong inhibitors",
                                "strong inducers"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "15. Vaccination with a live vaccine within 28 days of the initiation of treatment.",
            "criterions": [
                {
                    "exact_snippets": "Vaccination with a live vaccine within 28 days of the initiation of treatment.",
                    "criterion": "live vaccine vaccination",
                    "requirements": [
                        {
                            "requirement_type": "time since vaccination",
                            "expected_value": {
                                "operator": "<",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "16. A candidate for hematopoietic stem cell transplantation. Participants are excluded if they had received an allogeneic stem cell transplantation within 6 months or have active graft-versus-host-disease requiring ongoing immunosuppression.",
            "criterions": [
                {
                    "exact_snippets": "A candidate for hematopoietic stem cell transplantation.",
                    "criterion": "hematopoietic stem cell transplantation candidacy",
                    "requirements": [
                        {
                            "requirement_type": "candidacy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Participants are excluded if they had received an allogeneic stem cell transplantation within 6 months",
                    "criterion": "allogeneic stem cell transplantation",
                    "requirements": [
                        {
                            "requirement_type": "time since transplantation",
                            "expected_value": {
                                "operator": "<",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "active graft-versus-host-disease requiring ongoing immunosuppression",
                    "criterion": "graft-versus-host-disease",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        },
                        {
                            "requirement_type": "treatment",
                            "expected_value": "ongoing immunosuppression"
                        }
                    ]
                }
            ]
        },
        {
            "line": "17. Participated in any investigational drug study within 28 days or not recovered from toxicity of any prior chemotherapy to Grade ≤ 1.",
            "criterions": [
                {
                    "exact_snippets": "Participated in any investigational drug study within 28 days",
                    "criterion": "participation in investigational drug study",
                    "requirements": [
                        {
                            "requirement_type": "time since participation",
                            "expected_value": {
                                "operator": "<=",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "not recovered from toxicity of any prior chemotherapy to Grade ≤ 1",
                    "criterion": "recovery from chemotherapy toxicity",
                    "requirements": [
                        {
                            "requirement_type": "toxicity grade",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "Grade"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "18. History of other active malignancies within 2 years of study entry, with the exception of adequately treated in-situ carcinoma of cervix; localized basal cell or squamous cell carcinoma of skin; or previous malignancy confined and treated locally (surgery or other modality) with curative intent.",
            "criterions": [
                {
                    "exact_snippets": "History of other active malignancies within 2 years of study entry",
                    "criterion": "active malignancies",
                    "requirements": [
                        {
                            "requirement_type": "timeframe",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "adequately treated in-situ carcinoma of cervix",
                    "criterion": "in-situ carcinoma of cervix",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "adequately treated"
                        }
                    ]
                },
                {
                    "exact_snippets": "localized basal cell or squamous cell carcinoma of skin",
                    "criterion": "basal cell or squamous cell carcinoma of skin",
                    "requirements": [
                        {
                            "requirement_type": "localization",
                            "expected_value": "localized"
                        }
                    ]
                },
                {
                    "exact_snippets": "previous malignancy confined and treated locally (surgery or other modality) with curative intent",
                    "criterion": "previous malignancy",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "confined and treated locally with curative intent"
                        }
                    ]
                }
            ]
        },
        {
            "line": "19. Major surgery in the past 4 weeks prior to the first day of screening.",
            "criterions": [
                {
                    "exact_snippets": "Major surgery in the past 4 weeks prior to the first day of screening.",
                    "criterion": "major surgery",
                    "requirements": [
                        {
                            "requirement_type": "time since occurrence",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "20. Active and symptomatic fungal, bacterial, and/or viral infection; human T-cell lymphotropic virus type 1 seropositive status.",
            "criterions": [
                {
                    "exact_snippets": "Active and symptomatic fungal, bacterial, and/or viral infection",
                    "criterion": "infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "symptomatic",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "human T-cell lymphotropic virus type 1 seropositive status",
                    "criterion": "human T-cell lymphotropic virus type 1",
                    "requirements": [
                        {
                            "requirement_type": "seropositive status",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "21. Human immunodeficiency virus (HIV) infection, or active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] detected. • Hepatitis B/C serologic markers and viral load will be tested at screening. The hepatitis B testing includes HBsAg, HBcAb, and HBsAb as well as hepatitis B virus (HBV) DNA by Polymerase chain reaction (PCR) if the participant is negative for HBsAg but HBcAb positive (regardless of HBsAb status). The hepatitis C testing includes Hepatitis C virus (HCV) antibody as well as HCV RNA by PCR if the Participant is HCV antibody positive. Participants with positive HBsAg and/or detectable level of HBV DNA or detectable level of HCV RNA (≥ 15 IU/mL) are not eligible. Participants negative for HBsAg, HBcAb positive, and HBV DNA negative must undergo monthly HBV DNA screening by PCR. Participants positive for HCV antibody but negative for HCV RNA (defined as < 15 IU) must undergo monthly HCV RNA screening.",
            "criterions": [
                {
                    "exact_snippets": "Human immunodeficiency virus (HIV) infection",
                    "criterion": "HIV infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "active hepatitis B",
                    "criterion": "active hepatitis B",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "hepatitis B surface antigen [HBsAg] reactive",
                    "criterion": "HBsAg reactivity",
                    "requirements": [
                        {
                            "requirement_type": "reactivity",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "hepatitis C",
                    "criterion": "hepatitis C",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "hepatitis C virus [HCV] ribonucleic acid [RNA] detected",
                    "criterion": "HCV RNA detection",
                    "requirements": [
                        {
                            "requirement_type": "detection",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "positive HBsAg",
                    "criterion": "HBsAg positivity",
                    "requirements": [
                        {
                            "requirement_type": "positivity",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "detectable level of HBV DNA",
                    "criterion": "HBV DNA detectability",
                    "requirements": [
                        {
                            "requirement_type": "detectability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "detectable level of HCV RNA (≥ 15 IU/mL)",
                    "criterion": "HCV RNA detectability",
                    "requirements": [
                        {
                            "requirement_type": "detectability",
                            "expected_value": {
                                "operator": ">=",
                                "value": 15,
                                "unit": "IU/mL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "negative for HBsAg, HBcAb positive, and HBV DNA negative",
                    "criterion": "HBsAg negativity, HBcAb positivity, HBV DNA negativity",
                    "requirements": [
                        {
                            "requirement_type": "negativity",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "positivity",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "negativity",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "positive for HCV antibody but negative for HCV RNA (defined as < 15 IU)",
                    "criterion": "HCV antibody positivity, HCV RNA negativity",
                    "requirements": [
                        {
                            "requirement_type": "positivity",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "negativity",
                            "expected_value": {
                                "operator": "<",
                                "value": 15,
                                "unit": "IU"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "22. Inability to comply with study procedures.",
            "criterions": [
                {
                    "exact_snippets": "Inability to comply with study procedures.",
                    "criterion": "compliance with study procedures",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "23. Pregnant or nursing women.",
            "criterions": [
                {
                    "exact_snippets": "Pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "nursing women",
                    "criterion": "nursing",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "24. Men or women of childbearing potential who refuse to use an adequate measure of contraception, unless they have past medical history of surgical sterilization.",
            "criterions": [
                {
                    "exact_snippets": "Men or women of childbearing potential",
                    "criterion": "childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "refuse to use an adequate measure of contraception",
                    "criterion": "contraception usage",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "past medical history of surgical sterilization",
                    "criterion": "surgical sterilization",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "25. Currently taking or plan to take CNS penetrant therapy such as thiotepa, cytarabine, or partially CNS penetrant agents known to be active in lymphoid tumors, such as rituximab.",
            "criterions": [
                {
                    "exact_snippets": "Currently taking or plan to take CNS penetrant therapy",
                    "criterion": "CNS penetrant therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "CNS penetrant therapy such as thiotepa, cytarabine",
                    "criterion": "CNS penetrant therapy agents",
                    "requirements": [
                        {
                            "requirement_type": "examples",
                            "expected_value": [
                                "thiotepa",
                                "cytarabine"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "partially CNS penetrant agents known to be active in lymphoid tumors, such as rituximab",
                    "criterion": "partially CNS penetrant agents",
                    "requirements": [
                        {
                            "requirement_type": "examples",
                            "expected_value": [
                                "rituximab"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "26. Has taken or plans to take any chemotherapy, immunotherapy (eg, interleukin, interferon, thymoxin), or any investigational therapies to treat leukemia or lymphoma within 28 days or 5 half-lives (whichever is shorter) of the first study drug administration, including CNS penetrating agents.",
            "criterions": [
                {
                    "exact_snippets": "Has taken or plans to take any chemotherapy ... within 28 days or 5 half-lives (whichever is shorter) of the first study drug administration",
                    "criterion": "chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "within 28 days or 5 half-lives (whichever is shorter) of the first study drug administration"
                        }
                    ]
                },
                {
                    "exact_snippets": "Has taken or plans to take any ... immunotherapy (eg, interleukin, interferon, thymoxin) ... within 28 days or 5 half-lives (whichever is shorter) of the first study drug administration",
                    "criterion": "immunotherapy",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "within 28 days or 5 half-lives (whichever is shorter) of the first study drug administration"
                        }
                    ]
                },
                {
                    "exact_snippets": "Has taken or plans to take any ... investigational therapies to treat leukemia or lymphoma ... within 28 days or 5 half-lives (whichever is shorter) of the first study drug administration",
                    "criterion": "investigational therapies to treat leukemia or lymphoma",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "within 28 days or 5 half-lives (whichever is shorter) of the first study drug administration"
                        }
                    ]
                },
                {
                    "exact_snippets": "Has taken or plans to take any ... CNS penetrating agents ... within 28 days or 5 half-lives (whichever is shorter) of the first study drug administration",
                    "criterion": "CNS penetrating agents",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "within 28 days or 5 half-lives (whichever is shorter) of the first study drug administration"
                        }
                    ]
                }
            ]
        },
        {
            "line": "NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.",
            "criterions": [
                {
                    "exact_snippets": "Other protocol defined Inclusion/Exclusion criteria",
                    "criterion": "protocol defined criteria",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": [
        {
            "line": "Key Inclusion Criteria",
            "criterions": []
        },
        {
            "line": "Participants may be entered in the study only if they meet all of the following criteria:",
            "criterions": []
        },
        {
            "line": "2. Dose expansion for Cohorts 1 to 4: participants with either of the following relapsed or refractory WHO-classified lymphoid malignancies who have received at least 1 prior line of standard therapy: a. Cohort 1: GCB DLBCL, with cell of origin defined by either immunohistochemistry or gene expression profiling. b. Cohort 2: non-GCB DLBCL, with cell of origin defined by either immunohistochemistry or gene expression profiling. participants who have transformed to DLBCL from another histology may be enrolled into Cohort 3. c. Cohort 3: Transformed lymphoid malignancy, including but not limited to: i. Large cell transformation of chronic lymphocytic leukemia (Richter's transformation). ii. Large cell transformation of other WHO-classified indolent non-Hodgkin's lymphoma, including FL, or MZL. d. Cohort 4: Histologically confirmed primary central nervous system lymphoma (PCNSL) or secondary central nervous system lymphoma (SCNSL) of breast or testicular origin: i. Must be able to tolerate lumbar puncture and/or Ommaya taps. ii. Must have received at least 1 prior central nervous system (CNS)-directed therapy. iii. Presence of brain parenchymal and/or leptomeningeal disease.",
            "criterions": [
                {
                    "exact_snippets": "relapsed or refractory WHO-classified lymphoid malignancies",
                    "criterion": "WHO-classified lymphoid malignancies",
                    "requirements": [
                        {
                            "requirement_type": "condition",
                            "expected_value": [
                                "relapsed",
                                "refractory"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "have received at least 1 prior line of standard therapy",
                    "criterion": "prior line of standard therapy",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "line"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Cohort 1: GCB DLBCL, with cell of origin defined by either immunohistochemistry or gene expression profiling",
                    "criterion": "GCB DLBCL",
                    "requirements": [
                        {
                            "requirement_type": "cell of origin definition",
                            "expected_value": [
                                "immunohistochemistry",
                                "gene expression profiling"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Cohort 2: non-GCB DLBCL, with cell of origin defined by either immunohistochemistry or gene expression profiling",
                    "criterion": "non-GCB DLBCL",
                    "requirements": [
                        {
                            "requirement_type": "cell of origin definition",
                            "expected_value": [
                                "immunohistochemistry",
                                "gene expression profiling"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "participants who have transformed to DLBCL from another histology may be enrolled into Cohort 3",
                    "criterion": "transformation to DLBCL",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Cohort 3: Transformed lymphoid malignancy, including but not limited to: Large cell transformation of chronic lymphocytic leukemia (Richter's transformation)",
                    "criterion": "transformed lymphoid malignancy",
                    "requirements": [
                        {
                            "requirement_type": "examples",
                            "expected_value": [
                                "Large cell transformation of chronic lymphocytic leukemia (Richter's transformation)"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Large cell transformation of other WHO-classified indolent non-Hodgkin's lymphoma, including FL, or MZL",
                    "criterion": "large cell transformation of indolent non-Hodgkin's lymphoma",
                    "requirements": [
                        {
                            "requirement_type": "examples",
                            "expected_value": [
                                "FL",
                                "MZL"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Cohort 4: Histologically confirmed primary central nervous system lymphoma (PCNSL) or secondary central nervous system lymphoma (SCNSL) of breast or testicular origin",
                    "criterion": "central nervous system lymphoma",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": "histologically"
                        },
                        {
                            "requirement_type": "origin",
                            "expected_value": [
                                "breast",
                                "testicular"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Must be able to tolerate lumbar puncture and/or Ommaya taps",
                    "criterion": "tolerance to lumbar puncture and/or Ommaya taps",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Must have received at least 1 prior central nervous system (CNS)-directed therapy",
                    "criterion": "prior CNS-directed therapy",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "therapy"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Presence of brain parenchymal and/or leptomeningeal disease",
                    "criterion": "brain parenchymal and/or leptomeningeal disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Key Exclusion Criteria",
            "criterions": []
        },
        {
            "line": "Participants will not be entered in the study for any of the following reasons:",
            "criterions": []
        },
        {
            "line": "6. History of significant cardiovascular disease, defined as: a. Congestive heart failure greater than New York Heart Association (NYHA) class II according to the NYHA functional classification. b. Unstable angina or myocardial infarction with 6 months of enrollment. c. Serious cardiac arrhythmia or clinically significant ECG abnormality: corrected QT wave (QTcF) > 480 msec based on the Fridericia's formula or other ECG abnormalities including second-degree atrioventricular block type II, third-degree atrioventricular block. Participants who have a pacemaker will be allowed on study despite ECG abnormalities or the inability to calculate the QTc.",
            "criterions": [
                {
                    "exact_snippets": "History of significant cardiovascular disease, defined as: a. Congestive heart failure greater than New York Heart Association (NYHA) class II",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">",
                                "value": 2,
                                "unit": "NYHA class"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "History of significant cardiovascular disease, defined as: b. Unstable angina or myocardial infarction with 6 months of enrollment.",
                    "criterion": "unstable angina or myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "History of significant cardiovascular disease, defined as: c. Serious cardiac arrhythmia or clinically significant ECG abnormality: corrected QT wave (QTcF) > 480 msec based on the Fridericia's formula",
                    "criterion": "corrected QT wave (QTcF)",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 480,
                                "unit": "msec"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "History of significant cardiovascular disease, defined as: c. Serious cardiac arrhythmia or clinically significant ECG abnormality: ... other ECG abnormalities including second-degree atrioventricular block type II, third-degree atrioventricular block.",
                    "criterion": "ECG abnormalities",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "second-degree atrioventricular block type II",
                                "third-degree atrioventricular block"
                            ]
                        }
                    ]
                }
            ]
        }
    ]
}