--- a +++ b/clusters/3009knumclusters/clust_56.txt @@ -0,0 +1,202 @@ +Patients must not demonstrate any other signs indicative of pulmonary hemorrhage within 3 months prior to registration +Patients with active bleeding are not eligible; specifically, no clinically significant gastrointestinal (GI) bleeding, GI perforation, intra-abdominal abscess or fistula for 6 months prior to enrollment, no hemoptysis or other signs of pulmonary hemorrhage for 3 months prior to enrollment; patients with evidence of an acute intracranial or intratumoral hemorrhage on CT or MRI are not eligible (patients with evidence of resolving hemorrhage will be eligible); in patients with CNS tumors, an MRI with ECHO gradient sequences would be required to exclude presence of petechial hemorrhages +History of hemorrhage or hemoptysis (> ½ teaspoon bright red blood) within 3 months of starting study treatment +Patients with a history of stroke or intracranial hemorrhage within 6 months prior to registration are not eligible +Pulmonary hemorrhage or gross hemoptysis (bright red blood of >= 1/2 teaspoon per episode) within 6 months prior to enrollment +History of stroke within 6 months. +Patients whose screening MRI scan demonstrates intratumoral hemorrhage or peritumoral hemorrhage are not eligible for treatment if deemed significant by the treating physician +Grade 1 or higher CNS hemorrhage on baseline brain MRI, or history of grade 2 or higher CNS hemorrhage within 12 months +The subject has experienced any of the following:\r\n* Clinically-significant gastrointestinal (GI) bleeding within 6 months before the first dose of study treatment\r\n* Hemoptysis of >= 0.5 teaspoon (2.5 ml) of red blood within 3 months before the first dose of study treatment\r\n* Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment +Stroke. +Bleeding and thrombosis:\r\n* Patients with evidence of active bleeding: intratumoral hemorrhage by current imaging, or bleeding diathesis are not eligible\r\n* Patients with known or prior history in prior 3 months of esophageal varices are not eligible\r\n* Patients with a history of CNS arterial/venous thromboembolic events including transient ischemic attack (TIA) or cerebrovascular accident (CVA) within 6 months prior to study enrollment are not eligible\r\n* Patients with a history of deep vein thrombosis (including pulmonary embolism) within 3 months prior to study enrollment are not eligible\r\n* Patients with a history of hemoptysis or other signs of pulmonary hemorrhage within 3 months prior to study enrollment are not eligible\r\n* Patients with a history of >= grade 3 bleeding disorders, vasculitis, or had a significant (>= grade 3) episode from the gastrointestinal bleeding, within 6 months prior to enrollment are not eligible\r\n* For part B: patients with CNS tumors and evidence of new CNS hemorrhage of more than punctate size and/or more than three foci of punctate hemorrhage on baseline magnetic resonance imaging (MRI) obtained within 14 days prior to study enrollment are not eligible; Note: echocardiogram (ECHO) gradient MRI sequences per institutional guidelines are required for patients with CNS tumors +The participant has experienced any of the following:\r\n* Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment\r\n* Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood within 3 months before the first dose of study treatment\r\n* Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment +History of stroke or intracranial hemorrhage within 6 months prior to enrollment +History of stroke or intracranial hemorrhage within 6 months prior to enrollment +Recent (within 8 weeks) history of central nervous system (CNS) hemorrhage unless the hemorrhage is located within the tumor that will be removed en total during surgical debulking or ablated during MLA +History of stroke/intracranial hemorrhage =< 6 months prior to registration +Grade >= 3 hemorrhage within 4 weeks of patient randomization +History of intracranial abscess within 6 months prior to randomization. +History of stroke or intracranial hemorrhage within 6 months prior to randomization +History of stroke or intracranial hemorrhage within 6 months of first dose +Has history of known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhage within 12 months of start of study drug +The subject has experienced any of the following: a. clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment; b. hemoptysis >= 0.5 teaspoon (2.5 mL) of red blood within 3 months before the first dose of study treatment; c. any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment. Tumor invading any major blood vessel at the time of study enrollment. +Intracranial hemorrhage grade > 1 not attributable to recent neurosurgery +History of stroke or intracranial hemorrhage within 6 months prior to enrollment +The subject has any of the following risks of bleeding:\r\n* Clinically-significant gastrointestinal (GI) bleeding within 6 months before enrollment\r\n* Hemoptysis of >= 0.5 teaspoon (2.5 ml) of red blood within 3 months enrollment\r\n* Any other signs indicative of pulmonary hemorrhage within 3 months before enrollment\r\n* Radiographic evidence of cavitating pulmonary lesion(s) +The subject has experienced any of the following:\r\n* Clinically-significant gastrointestinal (GI) bleeding within 6 months before the first dose of study treatment\r\n* Hemoptysis of >= 0.5 teaspoon (2.5 ml) of red blood within 3 months before the first dose of study treatment\r\n* any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment; and\r\n* Clinically confirmed history of interstitial lung disease (ILD) +Any history of symptomatic intracranial hemorrhage. +Patients with recent cerebral hemorrhage +Patients should not have a stroke or intracranial hemorrhage within last 6 months +History of hemorrhage or hemoptysis (> ½ teaspoon bright red blood) within 3 months prior to study treatment +Grade 3 or 4 hemorrhage within the past 3 weeks +Patients will not be eligible if they have a history of intracranial hemorrhage in past 6 months +History of stroke or intracranial hemorrhage within 6 months prior to enrollment +Evidence of acute intracranial or intratumoral hemorrhage either by magnetic resonance imaging (MRI) or computed tomography (CT) scan; subjects with resolving hemorrhage changes, punctuate hemorrhage, or hemosiderin are eligible +History of ischemic stroke or intracranial hemorrhage =< 180 days prior to pre-registration +The subject has experienced any of the following: \r\n* Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment; \r\n* Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood within 3 months before the first dose of study treatment; \r\n* Any other signs indicative of hemorrhage within 3 months before the first dose of study treatment +Has history of known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhage within 12 months of registration +Has history bleeding disorders (e.g., pulmonary hemorrhage, significant hemoptysis, menometrorrhagia not responding to hormonal treatment) ? 2 months before C1D1 +History of stroke/intracranial hemorrhage =< 6 months prior to registration +History of stroke or intracranial hemorrhage within 6 months prior to enrollment +History of stroke or intracranial hemorrhage within 6 months of the first dose of study drug +History of stroke or intracranial hemorrhage within 6 months prior to enrollment +History of stroke or intracranial hemorrhage within 6 months before the first dose of study drug +History of stroke or intracranial hemorrhage within 6 months prior to enrollment +Subjects who had a prior intracranial hemorrhage, known arteriovenous malformation or aneurysm, head trauma, or evidence of active bleeding; +History of stroke or intracranial hemorrhage within 6 months prior to enrollment +History of known hemoptysis, gastrointestinal or intracerebral hemorrhage +History of stroke or intracranial hemorrhage within 6 months prior to enrollment +History of stroke or cerebral hemorrhage within 2 months +Evidence of acute intracranial / intra-tumoral hemorrhage, except for participants with stable grade 1 hemorrhage. +History of stroke or intracranial hemorrhage within 6 months prior to enrollment +History of stroke or intracranial hemorrhage within 6 months prior to randomization +Intracranial hemorrhage except for tumor associated micro hemorrhage. +History of stroke or intracranial hemorrhage within 6 months prior to study entry +History of stroke or cerebral hemorrhage within 6 months +History of intracranial hemorrhage (either by clinical history or neuroimaging) +The subject has experienced any of the following:\r\n* Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment\r\n* Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood within 3 months before the first dose of study treatment\r\n* Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment +History of hemorrhage or hemoptysis (> 1/2 teaspoon bright red blood) within 3 months of starting study treatment +History of stroke or cerebral hemorrhage within 2 month +Patients with treated supratentorial metastases are allowed if stable, the patient is off steroids and no evidence of intracranial hemorrhage +Patients with evidence of recent intratumoral hemorrhage (within 3 months of study enrollment), gastrointestinal bleeding, history of coronary artery disease or on anticoagulation therapy +The subject has experienced any of the following: a. clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment, b. hemoptysis of >= 0.5 teaspoon (2.5 ml) of red blood within 3 months before the first dose of study treatment, c. any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment +History of stroke or intracranial hemorrhage within 6 months of screening +The subject has experienced any of the following:\r\n* Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment\r\n* Hemoptysis of >= 0.5 teaspoon (2.5 ml) of red blood within 3 months before the first dose of study treatment\r\n* Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment +The subject has experienced any of the following:\r\n* Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment\r\n* Hemoptysis of >= 0.5 teaspoon (2.5ml) of red blood within 3 months before the first dose of study treatment\r\n* Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment +No history of intracranial hemorrhage +The subject has evidence of acute intracranial or intratumoral hemorrhage either by magnetic resonance imaging (MRI) or computerized tomography (CT) scan; subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin are eligible +Evidence of recent hemorrhage on screening MRI of the brain with the following exceptions: presence of hemosiderin; resolving hemorrhagic changes related to surgery; presence of punctate hemorrhage in the tumor +History of stroke within 6 months +Relapsed/refractory MCL: History of stroke or intracranial hemorrhage within 6 months prior to signing the consent +Newly diagnosed MCL: History of stroke or intracranial hemorrhage within 6 months prior to signing the consent +Contraindication to antiangiogenic agents, including:\r\n* Bronchopulmonary hemorrhage/bleeding event >= grade 2 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 4.0) within 4 weeks or less prior to first dose of study drug\r\n* Any other hemorrhage/bleeding event >= grade 3 (CTCAE version [v]4.0) within 4 weeks or less prior to first dose of study treatment\r\n* Radiological evidence of any intracranial hemorrhage within the 4 weeks or less prior to first dose of study treatment \r\n* History of significant intratumoral, intracerebral, or subarachnoid hemorrhage\r\n* Serious non-healing wound, ulcer, or bone fracture\r\n* Documented bowel perforation within 6 months of the start of study treatment +GI hemorrhage or obstruction experienced within the previous 6 weeks +History of stroke within 6 months +Evidence of recent (less than 2 weeks) intracranial hemorrhage. +History of intratumoral or peritumoral hemorrhage if deemed significant by the treating physician +Have evidence of significant (ie, symptomatic) intracranial hemorrhage. +History of stroke or intracranial hemorrhage within 6 months prior to enrollment +Known history of cerebrovascular accident, myocardial infarction, or intracranial hemorrhage within 2 months of enrollment. +History of stroke or intracranial hemorrhage within 6 months prior to enrolment +The subject has experienced any of the following:\r\n* Clinically-significant GI bleeding within 6 months before the first dose of study treatment\r\n* Hemoptysis of >= 0.5 teaspoon (2.5 ml) of red blood within 3 months before the first dose of study treatment\r\n* Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment +Has an ongoing or previous history of spontaneous intratumoral hemorrhage. +History of stroke or intracranial hemorrhage within 3 months prior to enrollment +History of stroke or intracranial hemorrhage within 6 months prior to signing the consent. +Subjects with history of known bleeding disorder(s) or history of clinically significant hemorrhage (e.g., gastrointestinal , neurologic), within the past 6 months. +Participants with history of known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhage within 12 months of start of study drug +The subject has experienced any of the following:\r\n* Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment\r\n* Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood within 3 months before the first dose of study treatment\r\n* Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment +History of stroke or intracranial hemorrhage within 6 months prior to enrollment +The subject has experienced clinically-significant hematemesis or hemoptysis of > 0.5 teaspoon of red blood, or other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment +The subject has experienced any of the following within 3 months before the first dose of\r\nstudy treatment:\r\n* Clinically-significant hematemesis or lower gastrointestinal bleeding\r\n* Hemoptysis of > 0.5 teaspoon of red blood\r\n* Any other signs indicative of pulmonary hemorrhage +History of stroke or intracranial hemorrhage within 6 months prior to enrollment +Subjects with a history of significant hemoptysis per the treating physician's judgment, cerebral hemorrhage or clinically significant gastrointestinal (GI) hemorrhage or myocardial infarction (MI) within the past 6 months +No signs indicative of pulmonary hemorrhage within 12 weeks before the first dose of study treatment +History of stroke within six months +Glioma patients with evidence of intracranial or intratumoral hemorrhage either by MRI or CT scan +History of stroke or intracranial hemorrhage within 6 months before randomization. +History of stroke or intracranial hemorrhage within 6 months before randomization. +history of stroke or intracranial hemorrhage within 6 months prior to enrollment +Previously experienced any of the following:\r\n* Clinically significant gastrointestinal bleeding within 6 months\r\n* Hemoptysis of >= 0.5 teaspoon (2.5 ml) of red blood within the last 3 months\r\n* Any other signs indicative of pulmonary hemorrhage within 3 months +Previously experienced any of the following:\r\n* Clinically significant gastrointestinal bleeding within 6 months before the first dose of study treatment\r\n* Hemoptysis of >= 0.5 teaspoon (2.5 ml) of red blood within 3 months before the first dose of study treatment\r\n* Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment +History of hemorrhage or hemoptysis (> ½ teaspoon bright red blood) within 3 months of starting study treatment +Evidence of recent hemorrhage on baseline MRI of the brain. However, patients with clinically asymptomatic presence of hemosiderin, resolving hemorrhagic changes related to surgery, or presence of punctuate hemorrhage in the tumor are eligible. +History of stroke or clinically significant intracranial hemorrhage within 6 months before first dose of study drug. +History of stroke or intracranial hemorrhage within 6 months prior to enrollment +Evidence of CNS hemorrhage on baseline MRI or CT scan (except for post-surgical, asymptomatic Grade 1 hemorrhage that has been stable for at least 3 months for subjects enrolled prior to Amendment 2 and for at least 4 weeks in subjects enrolled after Amendment 2 is approved). +No stroke or intracranial hemorrhage within the last 6 months +History of stroke or intracranial hemorrhage within 6 months prior to enrollment +History of hemorrhage or hemoptysis (> ½ teaspoon bright red blood) within 3 months of starting study treatment +History of stroke or intracranial hemorrhage within 6 months prior to enrollment +History of stroke or intracranial hemorrhage within 6 months prior to enrollment. +History of stroke or intracranial hemorrhage within 6 months prior to enrollment +History of stroke or cerebral hemorrhage within 6 months +The subject has experienced any of the following within 3 months before the first dose of study treatment:\r\n* Clinically-significant hematemesis or gastrointestinal bleeding\r\n* Hemoptysis of >= 0.5 teaspoon (>= 2.5 mL) of red blood\r\n* Any other signs indicative of pulmonary hemorrhage +History of intratumoral or peritumoral hemorrhage if deemed significant by the treating physician +Magnetic resonance imaging (MRI) echocardiogram (ECHO) gradient sequences are required to evaluate for the presence or absence of central nervous system (CNS) hemorrhage; patients with intra-tumoral and/or CNS hemorrhage are not eligible for study entry except:\r\n* Patients with asymptomatic intra-tumoral hemorrhage of punctate size, at the time of diagnosis, after surgery, and/or any time during protocol therapy\r\n* Patients with asymptomatic post-operative hemorrhage in and/or around the surgical cavity are eligible for study entry; additional imaging studies are not required, but in the event a repeat MRI is performed for clinical reasons the post-operative hemorrhage must not have progressed +At an increased risk of hemorrhage +History of pulmonary hemorrhage or hemoptysis within 6 months of starting study treatment +Patient has history of stroke or intracranial hemorrhage =< 6 months from starting study drugs +History of stroke or intracranial hemorrhage within 6 months prior to enrollment +History of stroke or intracranial hemorrhage within 6 months prior to the first dose of study drug +History of stroke or intracranial hemorrhage within 6 months prior to enrollment +History of stroke or intracranial hemorrhage within 6 months prior to study entry +History of stroke or cerebral hemorrhage within 2 months +Active intracranial hemorrhage +Gastrointestinal (GI) hemorrhage (active or in recent 6 months) +The subject has evidence of acute intracranial or intratumoral hemorrhage either by magnetic resonance imaging (MRI) or computed tomography (CT) scan; subjects with resolving hemorrhage, punctate hemorrhage, or hemosiderin are eligible +Has history of known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhage within 12 months of start of study drug +History of stroke or intracranial hemorrhage within 6 months prior to the first dose of ibrutinib +History of stroke or intracranial hemorrhage within 6 months prior to enrollment. +History of stroke or intracranial hemorrhage within 12 months prior to enrollment. +Subjects with a history of stroke or intracranial hemorrhage within 6 months prior to enrollment are not eligible +History of stroke or intracranial hemorrhage within 6 months prior to randomization +Subjects with severe (immediately life threatening) and recent (occurring within the last 3 months) cardiac dysfunction, pulmonary dysfunction, esophageal variceal bleeding, hemorrhagic strokes, or intracranial hemorrhage are not eligible for study participation +Evidence of new intracranial hemorrhage of more than punctate size on MRI assessment obtained within 28 days prior to study enrollment for Participants with HGG +History of stroke or intracranial hemorrhage within 6 months prior to enrollment +History of stroke or intracranial hemorrhage within 6 months prior to random assignment +Grade 3 or 4 hemoptysis or hemorrhage within 4 weeks prior to study entry +History of Grade 2 (CTCAE v4) or greater acute intracranial hemorrhage. +Active gastrointestinal (GI) or intracranial hemorrhage +The subject has experienced any of the following:\r\n* Clinically-significant hematemesis or gastrointestinal bleeding within 6 months before the first dose of study treatment\r\n* Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood within 3 months before the first dose of study treatment\r\n* Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment +History of stroke or intracranial hemorrhage within 6 months prior to randomization; or clinically significant cardiovascular disease +The participant has experienced any of the following within 3 months before the first dose of study treatment:\r\n* Clinically-significant hematemesis or lower gastrointestinal bleeding\r\n* Hemoptysis of >= 0.5 teaspoon (2.5 ml) of red blood\r\n* Any other signs indicative of pulmonary hemorrhage +History of stroke within 6 months prior to study registration +The subject has a history of clinically significant hematemesis or a recent history of hemoptysis of > 2.5 mL of red blood or other signs indicative of pulmonary hemorrhage or evidence of endobronchial lesion(s) +History of stroke within 6 months of registration +Patients whose MRI scan demonstrates intratumoral hemorrhage or peritumoral hemorrhage are not eligible for treatment if deemed significant by the treating physician +Evidence of frank hemorrhage or impending herniation on baseline brain imaging; NOTE: asymptomatic micro-hemorrhage is allowed +Patients under treatment with anticoagulants or with coagulation disorders or with signs of hemorrhage at baseline +History of stroke within 6 months prior to day 1 +History of stroke or intracranial hemorrhage within 6 months prior to enrollment +Patients under treatment with anticoagulants or with coagulation disorders or with signs of hemorrhage at baseline +History of stroke +History of stroke or intracranial hemorrhage within 6 months of screening would be exclusion for ibrutinib therapy but idelalisib would be an option +History of stroke or intracranial hemorrhage within 6 months prior to registration +History of stroke or intracranial hemorrhage within 6 months prior to enrollment +Patients with a history of known stroke or intracranial hemorrhage within 6 months prior to study treatment are excluded +History of stroke or intracranial hemorrhage within 6 months prior to enrollment. +Evidence of recent hemorrhage on post-operative contrast enhanced brain MRI (except hemosiderin, resolving hemorrhage changes related to surgery, presence of punctuate hemorrhage in tumor). +History of stroke or intracranial hemorrhage within 6 months prior to enrollment +Patients with recent history of hemorrhage and patients predisposed to hemorrhage due to coagulopathies or structural anomalies. +The subject has experienced any of the following:\r\n* Clinically significant gastrointestinal bleeding within 6 months before the first dose of study treatment\r\n* Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood within 3 months before the first dose of study treatment\r\n* Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment +History of stroke within 6 months +The subject has experienced any of the following:\r\n* Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment\r\n* Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood within 3 months before the first dose of study treatment\r\n* Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment +Subject has had clinically-significant hematemesis or hemoptysis of > 0.5 teaspoon of red blood, or other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment +Subjects with severe hemorrhage, or history of severe hemorrhage +History of stroke or intracranial hemorrhage within 6 months prior to enrollment +Has history of known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhage within 12 months of start of study drug. +Pulmonary hemorrhage of Grade ?2 within 28 days prior to first dose of study treatment +Any other hemorrhage or bleeding of Grade ?3 within 28 days prior to first dose of study treatment +History of stroke within 6 months prior to study enrollment. +Any known history of cerebrovascular disease including TIA, stroke or subarachnoid hemorrhage +The subject has experienced any of the following within 6 months before the first dose of study treatment:\r\n* Clinically significant hematemesis or gastrointestinal bleeding\r\n* Hemoptysis of >= 0.5 teaspoon (2.5 ml) of red blood\r\n* Any other signs indicative of pulmonary hemorrhage +Patients with a history of intracranial hemorrhage are not eligible. +Patient is at increased bleeding risk due to concurrent conditions (eg, major injuries or surgery within the past 28 days prior to start of study treatment, history of CVA, transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 3 months). +Pulmonary hemorrhage or gross hemoptysis within 12 months +Evidence of central nervous system (CNS) hemorrhage on baseline MRI or computed tomography (CT) scan (except for grade 1 hemorrhage that has been stable for at least 3 months) +History of stroke within six months +Pulmonary hemorrhage or gross hemoptysis within 6 months prior to enrollment +Subject has uncontrolled hemorrhage +In patients with CNS tumors or known CNS metastases, evidence of intracranial or intratumoral hemorrhage of more than punctuate size and/or more than 3 foci of punctuate hemorrhage on baseline magnetic resonance imaging (MRI) obtained within 14 days prior to study registration +History of stroke or intracranial hemorrhage =< 6 months prior to registration +History of stroke or intracranial hemorrhage within 6 months prior to treatment +History of stroke or cerebral hemorrhage within 2 months +No evidence of recent hemorrhage at pre-registration MRI of the brain, however the following are permitted: presence of hemosiderin, resolving hemorrhagic changes related to surgery, and presence of punctate hemorrhage in the tumor +Evidence of significant intracranial hemorrhage +History of stroke or intracranial hemorrhage within 6 months of enrollment +Evidence of recent (less than 2 weeks) hemorrhage on postoperative MRI of the brain; however, patients with clinically asymptomatic presence of hemosiderin, resolving hemorrhagic changes related to surgery, and presence of punctate hemorrhage in the tumour are permitted entry into the study +History of stroke +History of CNS hemorrhage within 28 days of study entry. This criterion may be waived at the investigator's request if the CNS hemorrhage was asymptomatic, with approval of the Medical Monitor +History of stroke or intracranial hemorrhage within 6 months prior to enrollment +History of stroke or intracranial hemorrhage within 6 months prior to enrollment +Diagnosis of intracranial hemorrhage within the past 3 months, including intratumoral hemorrhage into brain metastases from a systemic cancer +History of significant hemorrhage (requiring hospitalization or transfusion) outside of a surgical setting within the last 24 months +Any history of significant hemorrhage (requiring hospitalization or transfusion) within the last 6 months (excluding hemorrhage during operative procedure) +EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): History of stroke or intracranial hemorrhage within 6 months prior to screening +Stroke in the last six months +Patients must not have evidence of significant intracranial hemorrhage +History of stroke or intracranial hemorrhage within 6 months prior to enrollment +Patients with recent cerebral hemorrhage +Patients with recent cerebral hemorrhage +No hemorrhage after treatment. +History of stroke or intracranial hemorrhage within 6 months of first dose