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b'Male or female \\u2265 18 years age at the time of consent.' |
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b'Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 (Appendix 1).' |
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b'Has the ability to understand informed consent and provided signed written informed' |
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b'consent.' |
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b'Life expectancy of > 3 months.' |
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b'Histologically and/or cytologically confirmed advanced metastatic or unresectable' |
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b'olid tumors has progressed after treatment for which there are no standard therapies' |
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b'available OR histologically and/or cytologically confirmed hematological malignancies' |
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b'that have relapsed, or refractory disease following at least 2 standard lines of' |
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b'ystemic therapy for which there are no standard therapies available.' |
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b'Must have evaluable or measurable disease.' |
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b'Has all prior treatment (i.e., chemotherapy, immunotherapy, radiotherapy) related' |
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b'clinically significant toxicities resolve to \\u2264 Grade 1 per NCI CTCAE, Version 5.0 or' |
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b'are clinically stable and not clinically significant, at time of consent.' |
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b'All subjects must have completed any prior chemotherapy, targeted therapy and major' |
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b'urgery, \\u2265 28 days before study entry. For daily or weekly chemotherapy without the' |
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b'potential for delayed toxicity, a washout period of 14 days may be acceptable, and' |
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b'questions related to this can be discussed with the Medical Monitor.' |
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b'Has adequate hematologic (bone marrow [BM] and coagulation factors), and renal' |
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b'function.' |
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b'Able to swallow and retain orally-administered medication and without clinically' |
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b'ignificant gastrointestinal abnormalities that could alter absorption such as' |
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b'malabsorption syndrome or major resection of the stomach or bowels.' |
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b'Subjects with abnormal hepatic function will be eligible and will be grouped according' |
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b'to established criteria. Subjects with active hemolysis will be excluded.' |
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b'Manual differential with no significant morphologic abnormalities on complete blood' |
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b'count (CBC) testing.' |
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b'Male subjects must refrain from donating sperm starting at least 7 days before the' |
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b'planned first dose of tazemetostat until 3 months following the last dose of' |
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b'tazemetostat.' |
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b'Male subjects with a female partner of childbearing potential must:' |
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b'Be vasectomized, or' |
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b'Remain abstinent or use a condom starting at least 7 days before the planned' |
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b'first dose of IP until 3 months following the last dose of IP' |
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b'Female partners of male subjects who are of childbearing potential must also adhere to' |
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b'one of the following:' |
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b'Placement of an intrauterine device or intrauterine system.' |
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b'Established use of oral, injected, or implanted hormonal methods of contraception' |
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b'plus an additional barrier method.' |
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b'Progesterone-only oral contraception, where inhibition of ovulation is not the' |
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b'primary mode of action.' |
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b'Women of childbearing potential:' |
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b'Must agree to remain abstinent (refrain from heterosexual intercourse) or use' |
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b'contraceptive methods that result in a failure rate of < 1% per year starting at' |
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b'least 7 days before the planned first dose of IP until 6 months following the' |
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b'last dose of IP' |
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b'Due to the potential of enzyme induction with tazemetostat, female subjects who' |
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b'use hormonal contraceptives should use an additional barrier method of birth' |
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b'control while on study treatment and for 6 months after discontinuation of study' |
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b'treatment.' |
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b'Barrier methods must always be supplemented with the use of a spermicide.' |
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b'Females of childbearing potential must have a negative serum pregnancy test at' |
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b'creening.' |
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b"Has a QT interval corrected by Fridericia's formula (QTcF) \\u2264450 msec." |
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b'Subjects with diagnosed human immunodeficiency virus (HIV) are eligible to participate' |
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b'in the study if they meet the following criteria:' |
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b'No history of AIDS-defining opportunistic infections, or have not had an' |
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b'opportunistic infection within the past 12 months prior to enrollment.' |
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b"No history of AIDS-defining cancers (eg Kaposi's sarcoma, aggressive B-cell" |
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b'lymphoma, and invasive cervical cancer).' |
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b'Subjects may take prophylactic antimicrobials, however subjects that are taking' |
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b'pecific antimicrobial drugs where there may be DDI or overlapping toxicities' |
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b'hould be excluded from study participation.' |
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b'Subjects should be on established anti-retroviral therapy for at least 4 weeks,' |
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b'and have an HIV viral load of < 400 copies/mL prior to enrollment.' |
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b'Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression'
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b'as documented by CT or MRI scan, analysis of cerebrospinal fluid or neurological exam.'
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b"Subject's with primary glioblastoma multiforme are excluded. NOTE: Subjects with"
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b'clinically stable brain metastases are eligible to enroll in the study.'
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b'Clinically significant bleeding diathesis or coagulopathy, including known platelet'
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b'function disorders. Subjects on anticoagulation with low molecular weight heparin are'
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b'allowed.'
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b'Known hypersensitivity to any of the components of tazemetostat.'
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b'Concurrent investigational agent or anticancer therapy. NOTE: megestrol (Megace) if'
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b'used as an appetite stimulant is allowed.'
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b'Concurrent treatment with bisphosphonates is permitted; however, treatment must'
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b'be initiated prior to the first dose of study therapy. Prophylactic use of'
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b'bisphosphonates in subjects without bone disease is not permitted, except for the'
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b'treatment of osteoporosis.'
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b'The concurrent use of all herbal supplements is prohibited during the study as'
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b'the composition, PK, and metabolism of many herbal supplements are unknown.'
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b'Uncontrolled intercurrent illness including, but not limited to, ongoing or active'
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b'infection, clinically significant bleeding diathesis or coagulopathy, including known'
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b'platelet function disorders, symptomatic congestive heart failure, unstable angina'
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b'pectoris, clinically significant cardiac arrhythmias, or psychiatric illness/social'
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b'ituations that would limit compliance with study requirements.'
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b'Have a known active infection with hepatitis B virus (HBV, as measured by positive'
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b'hepatitis B surface antigen, hepatitis C virus (HCV, as measured by positive hepatitis'
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b'C antibody), OR human T-cell lymphotropic virus 1. EXCEPTIONS: Subjects with a history'
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b'of hepatitis B or C who have normal ALT and are hepatitis B surface antigen negative'
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b'and/or have undetectable HCV RNA.'
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b'Subjects taking medications that are known potent CYP3A4 inducers/inhibitors'
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b"(including St. John's Wort)"
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b'Is unwilling to exclude grapefruit juice, Seville oranges and grapefruit from the diet'
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b'and all foods that contain those fruits from 24 hours prior to the first dose of study'
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b'drug until the last dose of study drug.'
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b'Any condition or medical problem in addition to the underlying malignancy and organ'
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b'dysfunction that the Investigator feels would pose unacceptable risk.'
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b'Has thrombocytopenia, neutropenia, or anemia of grade \\u22653 (per CTCAE 5.0 criteria) or'
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b'any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS).'
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b'Has abnormalities known to be associated with MDS (e.g. del 5q, chr 7 abn) and'
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b'multiple primary neoplasms (MPN) (e.g. JAK2 V617F) observed in cytogenetic testing and'
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b'DNA sequencing'
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b'Has a prior history of T-LBL/T-ALL.'
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b'Ingestion of alcohol within 72 hours prior to day 1, until the 72 hour PK time point'
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b'has been collected. Regular alcohol consumption must not exceed 16 units for males and'
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b'7 units for females per week (1 unit equals 340mL of beer, 115mL of wine, or 43 mL of'
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b'pirits).'
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b'History of drug abuse (including alcohol) within the last 6 months prior to screening.'
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b'Severe hepatic encephalopathy (Grade >2) or degree of central nervous system (CNS)'
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b'impairment which the Investigator considers sufficiently serious to interfere with the'
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b'informed consent, the conduct, the completion, or the results of this trial, or'
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b'constitutes an unacceptable risk to the subject.'
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b'History of liver transplantation.'
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b'Advanced ascites or ascites that require drainage and albumin supplementation, as'
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b'judged by the Investigator.'
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b'Acute damage of the liver with Grade 4 AST/ALT values at screening or admission'
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