The subject has any bleeding diathesis, or must take anticoagulants, or antiplatelet agents, including nonsteroidal anti inflammatory drugs (NSAIDs), at the time of the scheduled resection that cannot be stopped for surgery
The patient has experienced any grade 3-4 gastrointestinal bleeding within 3 months prior to randomization
Active bleeding or pathologic condition that carries a high risk of bleeding (e.g., hereditary hemorrhagic telangiectasia). Patients with bleeding cutaneous lesions not actively requiring transfusions are eligible. Patients who have been uneventfully anti-coagulated with low molecular weight heparin are eligible
No history of gastrointestinal bleeding (GI) bleeding requiring a blood transfusion, endoscopic or operative intervention
Patients with intestinal obstruction or gastrointestinal bleeding
Patients with evidence of active bleeding or bleeding diathesis will be excluded (Note: patients aged > 17 years with excess of 2.5 mL of hemoptysis are not eligible)
Active bleeding or pathologic condition that carries a high risk of bleeding. No bleeding diathesis.
Active uncontrolled bleeding
Clinically significant bleeding event within the last 3 months, unrelated to trauma, or underlying condition that would be expected to result in a bleeding diathesis.
Evidence of active bleeding or bleeding diathesis; recent hemoptysis (>= 1/2 teaspoon of red blood within 8 weeks before first dose of study drug)
Evidence of active bleeding or bleeding diathesis; recent hemoptysis (>= ½ teaspoon of red blood within 8 weeks before first dose of study drug)
Patients with an active, bleeding diathesis
Significant bleeding disorder;
Patients with a history of bleeding diathesis are ineligible
Any Grade >/=3 hemorrhage or bleeding event within 28 days of Day 1 of Cycle 1
Evidence of mucosal or internal bleeding or platelet transfusion refractory
Patients will be excluded if any of the following are present:\r\n* Evidence of active bleeding, intratumoral hemorrhage, or bleeding diathesis\r\n* History (within 6 months prior to study enrollment) of pulmonary embolism, deep vein thrombosis (DVT), or other venous thromboembolic event\r\n* History of hemoptysis within 6 weeks prior to study enrollment
Patients with known involvement of the CNS by malignancy will be included if there is no evidence of active bleeding or intratumoral hemorrhage on radiographic imaging
Any history of hereditary bleeding disorders
History of bleeding diathesis or clinically significant bleeding within 14 days prior to randomization.
Active bleeding diatheses.
History of hemolytic anemia or bleeding diathesis
Patients with any grade 3-4 gastrointestinal bleeding within 3 months prior to enrollment
Patients with an active, bleeding diathesis
Active gastrointestinal bleeding
Active bleeding disorder in the past 6 months.
PHASE II: History of bleeding diathesis; patients receiving anti-coagulation must be able safely interrupt treatment for tumor biopsy
Known hemorrhagic diathesis or active bleeding disorder
History of a bleeding disorder
Significant bleeding disorders.
Patients with evidence of significant mucosal or internal bleeding
No clinically significant bleeding (i.e. gastrointestinal [GI] bleed, intracranial bleeding) within 6 months or major surgery within 4 weeks; minor surgeries (i.e. port placement, cataract surgery) are allowed within 2 weeks
Subjects with a history of esophageal bleeding have varices that have been sclerosed or banded and no bleeding episodes have occurred during the prior 6 months.
History of bleeding disorders or thromboembolic events in prior 3 months
Subject has an underlying condition predisposing them to bleeding or currently exhibits signs of clinically significant bleeding
Subjects may not have a history of bleeding diathesis or abnormal sensitivity to ionizing radiation
Significant bleeding disorders within 6 months prior to administration of first dose of study drug, including but not limited to:\r\n* Hematemesis, hematochezia, melena or other gastrointestinal bleeding >= grade 2 (per CTCAE version 4.03)\r\n* Hemoptysis or other pulmonary bleeding >= grade 2 (per CTCAE version 4.03)\r\n* Hematuria or other genitourinary bleeding >= grade 2 (per CTCAE version 4.03)
History of significant bleeding disorder unrelated to cancer
Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels
Patients with an active, bleeding diathesis or on oral anti-vitamin K medication (except low dose coumarin)
Active bleeding conditions
Active or prior documented GI bleeding (eg, esophageal varices or ulcer bleeding) within 12 months
Ongoing risk for bleeding due to active peptic ulcer disease or bleeding diathesis.
If receiving warfarin: INR ? 3.0 and no active bleeding (i.e., no bleeding within 14 days prior to first dose of study therapy).
Any grade 3-4 gastrointestinal (GI) bleeding within 3 months prior to enrollment
history of bleeding disorder
Vascular abnormalities or bleeding diathesis that indicates hepatic artery catheterization is contraindicated
History of bleeding disorders which would put a patient at risk for bleeding with anti-coagulation or patients with an increased risk of thromboembolic or hemorrhagic events (e.g., stroke).
Brain lesions or intracranial abnormalities at risk for bleeding, by history or radiologic imaging (e.g., active metastases).
Known bleeding disorders (e.g., von Willebrand’s disease) or hemophilia
History of significant bleeding disorder unrelated to chronic myelogenous leukemia (CML), including:\r\n* Diagnosed congenital bleeding disorders (e.g. von Willebrand’s disease) \r\n* Diagnosed acquired bleeding disorder within one year (e.g. acquired anti-factor VII antibodies)
History of upper GI bleeding, ulceration or perforation within 6 months before the first dose of defactinib.
Ongoing risk for bleeding due to active peptic ulcer disease, bleeding diathesis or requirement for systemic anticoagulation
Any grade >/=3 hemorrhage or bleeding event within 4 weeks prior to initiation of study treatment
Patients must not have a significant history of bleeding events\r\n* Patients with a history of a significant bleeding episode (e.g. hemoptysis, upper or lower gastrointestinal (GI) bleeding, grade 3 or 4 gross hematuria unable to be controlled by trans-urethral resection of the bladder tumor) within 6 months of registration are not eligible
Known bleeding disorders (e.g., von Willebrand’s disease) or hemophilia
Participants with inherited or acquired bleeding disorders
Patients with uncontrolled coagulopathies who are at increased risk of bleeding.
The patient has uncontrolled or severe coagulopathies or a history of clinically significant bleeding within the past 6 months, such as hemoptysis, epistaxis, hematochezia, hematuria, or gastrointestinal bleeding.
The patient has a known predisposition for bleeding such as von Willebrand's disease or other such condition.
Any hemorrhage or bleeding event ? grade 3 within 4 weeks.
Recent or active bleeding diathesis or arterial vascular event within 4 weeks
Known bleeding diathesis (eg, von Willebrand’s disease) or hemophilia
Personal history of endometrial cancer or any abnormal uterine bleeding
Major bronchial occlusion or bleeding not amenable to palliation
Patients with an active bleeding diathesis
Patients with coagulation problems and medically significant bleeding in the month prior to start of treatment (e.g., peptic ulcer, epistaxis, spontaneous bleeding). Prior history of DVT or PE is not exclusionary.
History of major gastrointestinal bleeding within the last 3 months or any evidence of active gastrointestinal bleeding excludes the subject.
History of significant bleeding disorder unrelated to cancer, including:\r\n* Diagnosed congenital bleeding disorders (e.g., von Willebrand’s disease)\r\n* Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)\r\n* Ongoing or recent (=< 3 months) significant gastrointestinal bleeding
Evidence of active bleeding or bleeding disorder
If they have had any active bleeding in the last =< 4 weeks or have an otherwise known bleeding diathesis
COHORT B, GROUP 6: HEPATOCELLULAR CARCINOMA: Variceal bleeding within last 6 months
Presence of GI bleeding.
Advanced primary with impeding occlusion, perforation or bleeding, dependent on transfusion
Abnormal bleeding times or active anti-coagulation therapy
History of hemolytic anemia or bleeding diathesis or positive direct antiglobulin test.
Requires therapeutic anticoagulation or has known active bleeding diathesis
Active gastrointestinal bleeding within previous 2 months
Active uncontrolled bleeding or a known bleeding diathesis
Uncontrolled severe bleeding tendency or active gastrointestinal (GI) bleeding
Platelets ? 50,000/mm^3 independent of transfusion support, with no active bleeding
History of active gastrointestinal bleeding within 6 months prior to randomization.
CRITERIA SPECIFIC FOR COHORT #2 (MCL): Known bleeding disorders (eg, von Willebrand's disease) or hemophilia
History of upper gastrointestinal (GI) bleeding from esophageal and/or gastric varices within 12 months before enrollment
Contraindication for ibrutinib use because of a bleeding diathesis.
Significant risk for bleeding
Bleeding disorders or active significant bleeding (i.e. hemoptysis, hematochezia, hematemesis) within 3 weeks
For cohort 3, any major bronchial occlusion or bleeding not amenable to palliation
For cohort 4, clinically significant hemorrhagic or ischemic stroke, including transient ischemic attacks and other central nervous system bleeding in the preceding 6 months that were not related to glioma surgery; history of prior intratumoral bleeding is not an exclusion criterion; however, patients with a history of prior intratumoral bleeding, will need to undergo a non-contrast head computed tomography (CT) to exclude acute bleeding
Normal coagulation profile and no history of substantial non-iatrogenic bleeding diathesis
Inability to tolerate aspirin, or other forms of anticoagulation, due to bleeding diathesis
History of upper gastrointestinal ulceration, upper gastrointestinal bleeding, or upper gastrointestinal perforation within the past 3 years; patients with ulceration, bleeding or perforation in the lower bowel are not excluded
Patients with higher risk of bleeding (deemed by the treating physician) or on anticoagulation
Evidence of a bleeding diathesis.
Patients with history of intra-abdominal bleeding or retroperitoneal bleeding within the last 3 years are excluded
Any Grade >=3 hemorrhage or bleeding event within 28 days of Day 1 of Cycle 1
GI Bleeding (eg, esophageal varices or ulcer bleeding) within 12 months
Known bleeding disorders
Patients with an underlying condition predisposing them to bleeding or currently exhibiting signs of clinically significant bleeding
Known inherited predisposition to bleeding or thrombosis
History of bleeding diathesis
History of significant bleeding disorder unrelated to cancer, including: \r\n* Diagnosed congenital bleeding disorders (e.g., von Willebrand’s’ disease) \r\n* Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies) \r\n* History of gastrointestinal (GI) bleeding within one year
Patients with known bleeding disorders or more than punctate intratumoral hemorrhage are excluded
Grade ? 3 hemorrhage or bleeding event within 28 days prior to initiation of study treatment
Active uncontrolled bleeding or a known bleeding diathesis
Subjects with untreated or incompletely treated varices with bleeding or high risk for bleeding; subjects treated with adequate endoscopic therapy (according to institutional standards) without any episodes of recurrent GI bleeding requiring transfusion or hospitalization for at least 6 months prior to enrollment are eligible
Patients must have normal coagulation profile and no history of substantial non-iatrogenic bleeding diathesis.
History of significant bleeding disorder unrelated to cancer, including: 1) diagnosed congenital bleeding disorders (e.g., von Willebrand’s disease); 2) diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies) of screening visit; 3) history of gastrointestinal (GI) bleeding within 3 months of screening visit requiring >= 2 units packed red blood cells.
Active bleeding or a pathological condition that is associated with a high risk of bleeding (therapeutic anticoagulation is allowed)
History of significant bleeding disorder unrelated to cancer, including: diagnosed congenital bleeding disorders (e.g., von Willebrand’s disease); diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies).
Patients with major gastrointestinal bleeding in the prior 2 months of enrollment.
Evidence or history of bleeding disorder.
Existing bleeding or condition associated with increased risk of bleeding
Any evidence of bleeding diathesis (patients on therapeutic warfarin or heparin will be excluded)
Patients with a history of bleeding disorders
Known bleeding disorders (e.g., von Willebrand’s disease or hemophilia)
Patients should not have transfusion-dependent thrombocytopenia or bleeding disorders
Active bleeding or pathologic condition that carries a high risk of bleeding (e.g., hereditary hemorrhagic telangiectasia)
History of significant bleeding disorder unrelated to cancer, including: diagnosed congenital bleeding disorders (e.g., von Willebrand’s disease, diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies, or ongoing or recent (=< 3 months) significant gastrointestinal bleeding
History of significant bleeding disorder unrelated to cancer, including: Diagnosed congenital bleeding disorders (e.g., von Willebrand’s disease); and diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies).
FOR ALL PHASES (Ib AND II): Patients with evidence or history of bleeding diathesis; any hemorrhage or bleeding event >= CTCAE grade 3 within 4 weeks of start of study medication
Evidence of active bleeding or bleeding diathesis
Patients on non-aspirin anti-coagulation (Coumadin, heparins, or clopidogrel) or with documented bleeding disorders will be excluded
Platelet count > 30,000 cells/mm^3 (30 x 10^9/L) without transfusion support; evidence of mucosal bleeding; a known bleeding episode within 3 months of screening; or a history of a bleeding disorder
Known bleeding disorders (eg, von Willebrand’s disease) or hemophilia
Patients with evidence or history of bleeding diathesis; any hemorrhage or bleeding event >= CTCAE grade 3 within 4 weeks before the start of study treatment
Known bleeding disorders (von Wilebrand’s disease or hemophilia)
Uncontrolled or severe coagulopathies or a history of clinically-significant bleeding within the past 6 months, including any of the following, but not limited to:\r\n* Epistaxis\r\n* Hemoptysis\r\n* Hematochezia\r\n* Hematuria\r\n* Gastrointestinal bleeding\r\n* Spontaneous or tumor related intracranial hemorrhage
Known predisposition for bleeding such as von Willebrand’s disease or other such condition(s)
Clinically significant bleeding within two weeks prior to randomization (e.g., gastrointestinal (GI) bleeding, intracranial hemorrhage)
History of clinically significant bleeding or known platelet or coagulation disorder
Platelets >= 50,000/mm^3 independent of transfusion support, with no active bleeding
Known bleeding disorders (e.g., von Willebrand’s disease) or hemophilia
Anti-coagulant therapy, bleeding or clotting disorder
Has an active bleeding disorders or evidence of chronic or acute disseminated intravascular coagulation (DIC)
History of significant congenital or acquired bleeding disorder unrelated to cancer
Grade 3 gastrointestinal (GI) bleeding within 3 months prior to screening
Known bleeding disorders
Known bleeding disorders (eg, von Willebrand’s disease) or hemophilia
Known history of bleeding diathesis
Needing medical attention for serious bleeding in past 4 weeks
Evidence or history of bleeding diathesis
Patients with an active bleeding diathesis
Patients with a history of peptic ulcer disease or gastrointestinal bleeding
Patients with any major bleeding current or within the past 4 weeks. (e.g. recent gastrointestinal [GI] hemorrhage or neurosurgery).
Subjects who within 21 days prior to randomization have had gastrointestinal or genitourinary bleeding;
Known inherited predisposition to bleeding or thrombosis
Documented or known bleeding disorder.
Known bleeding disorders (e.g., von Willebrand’s disease) or hemophilia
Patients with a history of gastrointestinal bleeding (GIB) within 6 weeks prior to registration are not eligible
Evidence or history of bleeding diathesis (greater than normal risk of bleeding, i.e., Hereditary Hemorrhagic Telangiectasia type I or HHT-1) or coagulopathy in the absence of therapeutic anti-coagulation or any hemorrhage/bleeding event > grade 3 within 4 weeks prior to registration; note: patients with full-dose anticoagulants are eligible provided the patient has been on a stable dose for at least 2 weeks of low molecular weight heparin; therapeutic Coumadin and aspirin doses > 325 mg daily are not allowed
Patients with an active bleeding diathesis
Have a significant bleeding disorder or vasculitis or had a Grade ?3 bleeding episode within 12 weeks prior to enrollment.
Significant bleeding disorders within 6 months prior to administration of first dose of study drug, including but not limited to:\r\n* Hematemesis, hematochezia, melena or other gastrointestinal bleeding > grade 2 \r\n* Hemoptysis or other pulmonary bleeding > grade 2 \r\n* Hematuria or other genitourinary bleeding > grade 2
Patient on anticoagulation or with bleeding diathesis due to risk of hematomas at injection site
Any history of significant bleeding disorder unrelated to cancer, including any congenital bleeding disorder or any acquired bleeding disorder within one year of start of study
No history of diagnosed congenital bleeding disorders (e.g., von Willebrand’s disease)
No abnormalities no history of diagnosed acquired bleeding disorders within one year (e.g., acquired anti-factor VIII antibodies) of registration on protocol therapy
No abnormalities no history of ongoing or recent (less than or equal to 3 months of registration on protocol therapy) significant gastrointestinal bleeding
Patients with evidence of bleeding diathesis are not eligible
Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia
Known abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants precluding intramuscular injections of fulvestrant or goserelin (if applicable)
The patient has significant bleeding disorders, vasculitis, or experienced grade 3/4 gastrointestinal (GI) bleeding within 3 months prior to enrollment
For patients undergoing serial tumor biopsies, known bleeding diathesis or history of abnormal bleeding or require anti-coagulation therapy which cannot be interrupted for biopsy
Any active bleeding in the last =< 4 weeks or have an otherwise known bleeding diathesis
Patients meeting the following criteria are not eligible unless cleared by cardiology: \r\n* Uncontrolled angina within 3 months\r\n* Diagnosed or suspected congenital long QT syndrome\r\n* Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)\r\n* Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (> 460 msec) \r\n* History of significant bleeding disorder unrelated to cancer, including: \r\n** Diagnosed congenital bleeding disorders (e.g., von Willebrand’s disease) \r\n** Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
No active bleeding
Major bleeding in the last 4 weeks prior to study entry
PHASE II DOSE EXPANSION IN RECURRENT GBM UNDERGOING RESECTION: Evidence of bleeding diathesis or use of anticoagulant medication or any medication that may increase the risk of bleeding that cannot be stopped prior to surgery
History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e., in the absence of therapeutic anticoagulation); current or recent (within 10 days of study enrollment) use of anticoagulants that, in the opinion of the investigator, would place the subject at significant risk for bleeding; prophylactic use of anticoagulants is allowed
Documented or known bleeding disorder.
Patients with evidence or history of bleeding diathesis; any hemorrhage or bleeding event >= CTCAE grade 3 within 4 weeks of start of study enrollment
Known bleeding disorders (e.g., von Willebrand’s disease) or hemophilia
Patient has any bleeding diathesis, or must take anticoagulants or antiplatelet agents, including nonsteroidal anti inflammatory drugs, that cannot be stopped for biopsy or surgery.
Major bleeding within the last 6 months.
Subjects with bleeding diatheses, thrombocytopenia or current anticoagulant use
The patient has experienced any grade 3-4 gastrointestinal (GI) bleeding within 3 months prior to enrollment
No bleeding from gastrointestinal ulcers or other sites of bleeding
Evidence or history of bleeding diathesis
For subjects with CNS involvement (primary tumor or metastatic disease), have any active bleeding or new intratumoral hemorrhage of more than punctuate size of screening MRI obtained within 14 days of starting study drug or known bleeding diathesis or treatment with anti-platelet or anti-thrombotic agents
Must not have any evidence of bleeding diathesis or active gastrointestinal bleeding
Personal or family history of bleeding diathesis and a coagulation profile that would preclude patient from undergoing a neurosurgical procedure
Patients must not have had any active bleeding in the last =< 4 weeks or have an otherwise known bleeding diathesis
Patients with active hemoptysis, clinically significant non hemorrhoidal gastrointestinal (GI) bleeding or those with bleeding diathesis
History of symptomatic gastrointestinal disorder within the last five years resulting in bleeding or chronic or frequent diarrhea
History of bleeding disorder or diathesis
Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)
Presence of bleeding diathesis
Active and significant bleeding
Active bleeding or pathologic condition that carries a high risk of bleeding (e.g. hereditary hemorrhagic telangiectasia); patients who have been uneventfully anti-coagulated with low molecular weight heparin are eligible
Evidence of active bleeding or bleeding diathesis
No active uncontrolled bleeding/bleeding diathesis
Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)
Active bleeding diathesis or history of major bleeding, central nervous system (CNS) bleeding, or significant hemoptysis within the past 6 months
Known inherited predisposition to bleeding or thrombosis
Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)
Evidence of active bleeding or bleeding diathesis
Documented or known bleeding disorder.
Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)
Active gastrointestinal bleeding
Evidence of uncontrollable bleeding diathesis
Subject has an underlying condition predisposing them to bleeding or currently exhibits signs of clinically significant bleeding
History or presence of any significant bleeding disorders
History of significant bleeding disorder unrelated to cancer, including:\r\n* Diagnosed congenital bleeding disorders (e.g., von Willebrand’s disease)\r\n* Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
Any active uncontrolled bleeding or bleeding diathesis (e.g., active peptic ulcer disease)
Evidence of bleeding diathesis or use of anticoagulant medication or any medication that may increase the risk of bleeding that cannot be stopped prior to surgery
Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)
Patients with evidence of active bleeding, intratumoral hemorrhage or history of bleeding diatheses, unless specifically occurring as an isolated incident during reversible chemotherapy-induced thrombocytopenia
History of significant bleeding disorder unrelated to cancer
History of significant bleeding disorder unrelated to cancer, including:\r\n* Diagnosed congenital bleeding disorders (e.g., von Willebrand’s disease)\r\n* Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)\r\n* Ongoing or recent (=< 3 months) significant gastrointestinal bleeding
Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as a known bleeding disorder, coagulopathy, or tumor involving major vessels
Evidence of active bleeding or bleeding diathesis
History of significant bleeding disorder unrelated to cancer, including diagnosed congenital bleeding disorders (e.g., von Willebrand’s disease), or diagnosed acquired bleeding disorders within one year (e.g., acquired anti-factor VIII antibodies)
Clinically significant hemorrhagic or ischemic stroke, including transient ischemic attacks and other central nervous system bleeding in the preceding 6 months that were not related to glioma surgery; history of prior intratumoral bleeding is not an exclusion criteria; patients who with history of prior intratumoral bleeding, however, need to undergo a non-contrast head computed tomography (CT) to exclude acute bleeding
History of significant bleeding disorder unrelated to cancer, including:\r\n* Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)\r\n* Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
Patients with a history of bleeding disorders or evidence of intracranial abnormalities which would put them at risk for bleeding with anti-coagulation (e.g., strokes, active metastases).
Grade 3 or higher bleeding event =< 3 months prior to randomization
Known bleeding disorders (e.g., von Willebrand’s disease) or hemophilia
Patients with an active bleeding diathesis
Bleeding diathesis, not correctable by usual forms of therapy
Bleeding diathesis, not correctable by usual forms of therapy
Active uncontrolled bleeding or a known bleeding diathesis
History of significant bleeding disorder or uncontrolled seizures
Clinical evidence of portal hypertension with bleeding esophageal or gastric varices at Screening, or within 6 months before randomization
Subject has an underlying bleeding disorder
Active bleeding diatheses which in the opinion of the treating physician poses a significantly increased operative risk.
active bleeding or a high risk of bleeding contraindicating anticoagulant treatment;
Have active uncontrolled bleeding or a known bleeding disorder
Patients with coagulation problems and active bleeding in the last month prior to cycle 1 day 1 (peptic ulcer, epistaxis, spontaneous bleeding)
Clinically significant bleeding event within the last 3 months, unrelated to trauma, or underlying condition that would be expected to result in a bleeding diathesis
Gastrointestinal bleeding within the past one year
Evidence of active mucosal or internal bleeding.
History or evidence of bleeding disorder or active clinically significant bleeding requiring medical intervention.
Severe bleeding, hemoptysis, gastrointestinal hemorrhage, CNS bleeding, clinically significant hemorrhage or vaginal bleeding during the last 6 months
If they have had any active bleeding in the last =< 4 weeks or have an otherwise known bleeding diathesis
Active uncontrolled bleeding or a known bleeding diathesis
Evidence of active mucosal or internal bleeding.
Lesions with underlying infection or clinically meaningful bleeding
Known abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants precluding intramuscular injections of fulvestrant or goserelin (if applicable).
Patients who have a history or current evidence of bleeding disorder, i.e., any hemorrhage/bleeding event of CTCAE grade >= 2, =< 28 days prior to registration
Patients with active or prior digestive tract bleeding.
Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)
Known bleeding disorders (e.g., von Willebrand’s disease) or hemophilia
Patients with an active, bleeding diathesis
Has a history of upper gastrointestinal ulceration, upper gastrointestinal bleeding, or upper gastrointestinal perforation within the past 3 years; subjects with ulceration, bleeding or perforation in the lower bowel are not excluded
Evidence of active bleeding or bleeding diathesis
History of significant congenital or acquired bleeding disorder unrelated to cancer
For subjects with CNS involvement (primary tumor or metastatic disease): Subjects must not have any active bleeding, or new intratumoral hemorrhage of more than punctate size on screening MRI or known bleeding diathesis or treatment with anti-platelet or anti-thrombotic agents
Known portal hypertension or history of variceal bleeding
Underlying condition predisposing them to bleeding or currently exhibits signs of clinically significant bleeding
Recent history of non-chemotherapy-induced thrombocytopenic-associated bleeding =< 1 year prior to the registration
Subjects with known bleeding diathesis will be excluded from the study.
Patients with history of bleeding diathesis are ineligible
Known, increased risk of bleeding
Subjects with history of bleeding diathesis
Patients with evidence of active bleeding or bleeding diathesis will be excluded (patients with excess of 2.5 mL of hemoptysis are not eligible)
Evidence of bleeding diathesis
Patients with an underlying condition predisposing them to bleeding or currently exhibiting signs of clinically significant bleeding
Active bleeding disorder or other history of significant bleeding episodes within 30 days before study entry
Patients with personal or family history of bleeding disorders are not eligible
Grade 2 or higher ongoing gastrointestinal hemorrhage; patients with grade 1 gastrointestinal bleeding are eligible for participation
Patients with evidence of active bleeding diathesis
Patients with evidence of active bleeding, intratumoral hemorrhage or history of bleeding diatheses, unless specifically occurring as an isolated incident during reversible chemotherapy-induced thrombocytopenia
Patients with evidence or history of bleeding diathesis; any hemorrhage or bleeding event >= CTCAE grade 3 within 4 weeks prior to registration
Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving (in contact with, invading or encasing) major vessels
Active bleeding or a pathological condition that is associated with a high risk of bleeding (therapeutic anticoagulation is allowed)
Patients with bleeding disorders are ineligible due to lymph node removal possibly causing excessive bleeding; bleeding disorder will be defined by an INR level of > 2.0
Known bleeding disorders (e.g., von Willebrand’s disease) or hemophilia
Any hemorrhage or bleeding event >= grade 3 within 4 weeks prior to prior to registration
Patients with coagulation problems and active major bleeding within 4 weeks prior to cycle 1, day 1 (C1D1) (peptic ulcer, epistaxis, spontaneous bleeding)
Patients with an active, bleeding diathesis
No evidence of active bleeding
History of significant bleeding disorder unrelated to cancer, including diagnosed congenital bleeding disorders (e.g., von Willebrand’s disease)
Patients with an active, bleeding diathesis
Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)
No history of abnormal bleeding tendency
Patients with an active, bleeding diathesis
Patients with an active, bleeding diathesis
No history of abnormal bleeding tendency or predisposition to repeated infections
Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels
Known hemorrhagic diathesis or active bleeding disorder
Patients with any pulmonary hemorrhage/bleeding event grade 2 or higher within 4 weeks before randomization
For subjects with CNS involvement (primary tumor or metastatic disease): Have any active bleeding, or new intratumoral hemorrhage of more than punctate size on Screening MRI obtained within 14 days of starting study drug,or known bleeding diathesis or treatment with anti-platelet or anti-thrombotic agents
This criterion applies only to the patients enrolled before August 29, 2011 and those enrolled after this date electing to receive bevacizumab; patients with active bleeding or pathologic conditions that carry high risk of bleeding such as a known bleeding disorder, coagulopathy, or tumor involving major vessels
Lung tumor lesions with increased likelihood of bleeding;
History of active bleeding within the last 3 months requiring transfusion
The participant has a significant bleeding disorder or vasculitis.
Has had esophageal or gastric variceal bleeding within the last 6 months.
History of CNS bleeding within 6 months of registration
Patients with active bleeding of the GI tract or patients who have symptoms associated with stomach irritation (known as gastritis).
Bleeding diathesis including clinically significant platelet disorders or active hemoptysis (defined as bright red blood of ? 1/2 teaspoon [2.5 mL] in any 24 hour period) within 6 months prior to study day 1. For clinically significant epistaxis within 4 weeks prior to study day 1, no risk of further bleeding must be clearly documented.
Active bleeding diathesis or history of any major bleeding, central nervous system (CNS) bleeding, or significant hemoptysis within 6 months of enrollment
Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels
Patients who have experienced any grade 3-4 gastrointestinal (GI) bleeding within 3 months prior to first dose of protocol therapy
Subjects with untreated or incompletely treated varices with bleeding or high risk for bleeding.
History of bleeding diathesis.
Known history of a bleeding diathesis.
Have a history of uncontrolled hereditary or acquired bleeding or thrombotic disorders.
known bleeding disorders or hemophilia
Evidence of active bleeding or bleeding diathesis
Evidence of active bleeding or bleeding diathesis
Active bleeding or pathologic condition that carries a high risk of bleeding (e.g. hereditary hemorrhagic telangiectasia). Patients who have been uneventfully anti-coagulated with low molecular weight heparin are eligible.
Bleeding disorder (INR > ULN and PTT > ULN)
Any history of clinically meaningful variceal bleeding within the last three months.
Evidence of bleeding diathesis
A history of bleeding (i.e., hemoptysis, hematuria, gastrointestinal blood loss, epistaxis, or others with greater than Grade 1 according to NCI CTCAE Version 4.03) within 1 month prior to beginning therapy or any clinical indications of current active bleeding.
Has active bleeding disorder or other history of significant bleeding episodes within 30 days of randomization.
Known inherited predisposition to bleeding or thrombosis
Patients must not have active bleeding or a pathological condition that is associated with a high risk of bleeding
History of major gastrointestinal bleeding within the last 6 months. Any evidence of active gastrointestinal bleeding excludes the subject.
No history of upper gastrointestinal ulceration, upper gastrointestinal bleeding, or upper gastrointestinal perforation within the past 3 years; patients with ulceration, bleeding or perforation in the lower bowel are NOT excluded
History of congenital bleeding diathesis
Significant hematologic, gastrointestinal, thromboembolic, vascular, bleeding, or coagulation disorders.
Patients with active bleeding or pathologic conditions that carry high risk of bleeding
Patients with active or uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (ITP) are excluded; patients who have transfusion-dependent thrombocytopenia or bleeding/coagulation disorders that may increase the risk of life-threatening bleeding are excluded
Known bleeding disorders (e.g., von Willebrand’s disease) or hemophilia
Anemia due to factors other than MDS, CMML, or AML (including hemolysis or gastrointestinal bleeding).
Patient has evidence of mucosal or internal bleeding and/or is platelet transfusion refractory
Active bleeding or pathologic condition that carries a high risk of bleeding (e.g. hereditary hemorrhagic telangiectasia).
Major upper gastrointestinal bleeding episode occurring during the previous year before screening.
Evidence of bleeding diathesis or clinically significant bleeding, within 28 days of C1D1 or history of hemoptysis of > 2.5 mL/1 teaspoon within 6 months of C1D1
A thrombotic or hemorrhagic event <=6 months prior to screening (includes hemoptysis, Gastrointestinal (GI) bleeding, hematemesis, central nervous system hemorrhage, epistaxis, vaginal bleeding, cerebral infarction, transient ischemic attacks, myocardial infarction, angina, and coronary artery disease)
have experienced any bleeding episode considered life-threatening, or any Grade 3 or 4 GI/variceal bleeding episode in the 3 months prior to enrollment requiring transfusion or endoscopic or operative intervention
Has had esophageal or gastric variceal bleeding within the last 6 months
Known bleeding disorders (eg, von Willebrand’s disease) or hemophilia
Active uncontrolled bleeding
Have significant bleeding disorders, vasculitis, or had a significant bleeding episode from the gastrointestinal tract within 12 weeks prior to randomization.
Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder or coagulopathy.
Known inherited predisposition to bleeding or thrombosis
For patients that are to undergo the tumour biopsy, a history of a hereditary bleeding disorder, or clinically relevant major bleeding event in the past 6 months, as judged by the investigator.
Patients at risk of non-AML related major bleeding (e.g. recent gastrointestinal [GI] hemorrhage or neurosurgery).
Active bleeding diathesis
History of gastrointestinal ulcer or bleeding within 3 months; any digestive tract dysfunction
Severe gastrointestinal bleeding within 12 weeks of treatment with G-202
Ongoing major bleeding,
History of significant bleeding disorder unrelated to cancer, including:\r\n* Diagnosed congenital bleeding disorders (e.g., von Willebrand’s disease)\r\n* Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
Gastrointestinal bleeding event or active hemoptysis (bright red blood of at least 0.5 teaspoon) within 28 days prior to randomization
Significant gastrointestinal bleeding within 6 weeks prior to consent.
Portosystemic hypertension or known history of bleeding esophageal varices.
Patients with an uncontrolled bleeding disorder
History of significant congenital or acquired bleeding disorder
Participant has a history of uncontrolled hereditary or acquired bleeding or thrombotic disorders
Patients with history of bleeding diathesis
History of hemolytic anemia or bleeding diathesis
In the opinion of the investigator, bleeding diathesis or anticoagulation therapy that would preclude intramuscular injections
History of active gastrointestinal (GI) bleeding or other major bleeding =< 12 months prior to randomization; Note: patients who do not have resolution of the predisposing risk factor (e.g., resection of a bleeding tumor, treatment and endoscopic documentation of a resolved ulcer) will also be excluded
Known inherited predisposition to bleeding or thrombosis
Have a significant bleeding disorder or vasculitis or had a Grade ?3 bleeding episode within 12 weeks prior to enrollment. Participants with a history of gross hemoptysis (defined as bright red blood of ?1/2 teaspoon) within 2 months prior to enrollment are excluded.
Patients with known bleeding diathesis (e.g. von Willebrand ‘s disease) or hemophilia
History of significant congenital or acquired bleeding disorder unrelated to cancer
History of major gastrointestinal bleeding within the last 6 months.
Evidence of history of bleeding diathesis.
Known bleeding disorders with the exception of acquired Von Willebrand disorder suspected on the basis of WM
Known bleeding disorders (e.g., von Willebrand disease or hemophilia)
Known bleeding diathesis (e.g., von Willebrand’s disease) or hemophilia
Subject has a history of bleeding esophageal varices within 3 months before the Day 1 visit.
Contraindications to prophylactic dose low molecular weight heparin (LMWH), including \r\n* Patients with recent gastrointestinal bleeding \r\n* History of heparin induce thrombocytopenia on LMWH\r\n* Subjects with previous severe hemorrhagic events on LMWH\r\n* Recent central nervous system bleed, intracranial or spinal lesion at high risk for bleeding\r\n* Active bleeding (major): more than 2 units transfused in 24 hours\r\n* Spinal anesthesia/lumbar puncture\r\n* Chronic, clinically significant measurable bleeding > 48 hours\r\n* Severe platelet dysfunction (uremia, medications, dysplastic hematopoiesis)\r\n* Recent major operation at high risk for bleeding\r\n* Underlying hemorrhagic coagulopathy\r\n* High risk for falls (head trauma)
Active bleeding diathesis
Patients with history of gastrointestinal (GI) bleeding and peptic ulcer disease within the past 6 months
Active bleeding disorders and high likelihood of bleeding or conditions or medications known to increase the risk of bleeding; patients with bleeding diathesis and subjects who are receiving anticoagulation treatment with INR > 2 are excluded
Evidence or history of bleeding diathesis or any hemorrhage or bleeding event > CTCAE grade 3 =< 4 weeks prior to randomization
Subjects with uncontrolled bleeding disorder which cannot be controlled with anticoagulants
Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels
Significant history of bleeding events or pre-existing bleeding diathesis =< 6 months of randomization (unless the source of bleeding has been resected)
Patients with a history of significant tumor bleeding, or coagulation or bleeding disorders.
The patient has significant bleeding disorders or vasculitis; history of significant (in the opinion of the investigator) upper gastrointestinal ulceration, upper gastrointestinal bleeding, or upper gastrointestinal perforation within the past 3 years; patients with a history of ulceration, bleeding or perforation in the lower bowel are not excluded
History of significant bleeding disorder unrelated to cancer
Patients with active bleeding diathesis
Concurrent medical conditions or injury which may increase the risk of toxicity, including ongoing or active infection, history of significant bleeding disorder unrelated to cancer (congenital bleeding disorders, acquired bleeding disorders within one year), history of human immunodeficiency virus (HIV)-positive, or active or chronic hepatitis C and/or B infection
Evidence of blood clotting or bleeding abnormalities
Known bleeding disorders or hemophilia.
Patients with coagulation problems and active bleeding in the last month (peptic ulcer, epistaxis, spontaneous bleeding)
Known bleeding disorders (eg, von Willebrand's disease) or hemophilia.
Patients with evidence or history of any bleeding diathesis, irrespective of severity
Subjects with a bleeding diathesis (e.g., von Willebrand’s disease or hemophilia) are not eligible
Subjects must not have clinically significant bleeding (i.e. gastrointestinal [GI] bleed, intracranial bleeding) within 6 months or have had major surgery within 4 weeks; minor surgeries (i.e. port placement, cataract surgery) are allowed if completed more than 2 weeks from the start of treatment
Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels
Evidence or history of tendency or predisposition to active bleeding. Any hemorrhage or bleeding event of Grade 3 or higher within 4 weeks of start of study medication;
Have a history of or active significant gastrointestinal (GI) bleeding within 3 months of the first dose of brigatinib.
Patients must not have any evidence of bleeding diathesis or active gastrointestinal bleeding
No patients with clinically significant gastrointestinal (GI) bleeding or bleeding diathesis within 30 days prior to registration
History of bleeding (i.e. disseminated intravascular coagulation or clotting factor deficiency);
Patient must not have any known bleeding disorders (e.g., von Willebrand’s disease) or hemophilia
Has had significant bleeding/thrombosis in previous 4 weeks
Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving (in contact with, invading or encasing) major vessels; patients who have experienced any of the following:\r\n* Clinically significant gastrointestinal bleeding within 6 months before 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
Patients with known bleeding disorders or more than punctate intratumoral hemorrhage are excluded
Patients requiring anticoagulation or with uncontrolled bleeding are excluded
History of upper gastrointestinal bleeding, ulceration, or perforation within 12 months prior to the first dose of study drug
Patients with evidence of a bleeding diathesis
Evidence of mucosal or internal bleeding
Evidence of active bleeding or bleeding diathesis
Concurrent medical conditions which may increase the risk of toxicity, including ongoing or active infection, history of significant bleeding disorder unrelated to cancer (congenital bleeding disorders, acquired bleeding disorders within one year), human immunodeficiency virus (HIV)-positive
Patients with untreated or incompletely treated varices with bleeding or high-risk for bleeding
Gastrointestinal bleeding or active hemoptysis (bright red blood of at least half teaspoon) within 21 days prior to enrollment
Known bleeding disorders (e.g. von Willebrand’s disease) or hemophilia
Any active uncontrolled bleeding or bleeding diathesis
Evidence of active bleeding or bleeding diathesis
Presence of transfusion-dependent thrombocytopenia or a history of bleeding disorders or clinical conditions (e.g. gastrointestinal [GI] bleeding or constitutional disorders) that may increase risk of life-threatening bleeding when thrombocytopenic
Known bleeding disorders (e.g., von Willebrand’s disease) or hemophilia
Significant bleeding disorders within 6 months prior to administration of first dose of study drug, including but not limited to:\r\n* Hematemesis, hematochezia, melena or other gastrointestinal bleeding >= grade 2 (per CTCAE version 4.0)\r\n* Hemoptysis or other pulmonary bleeding >= grade 2 (per CTCAE version 4.0)\r\n* Hematuria or other genitourinary bleeding >= grade 2 (per CTCAE version 4.0)
Clinical significant gastrointestinal bleeding in the 6 months prior to Cycle 1 Day 1 (C1D1) first dose
No clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding within 28 days prior to registration including, but not limited to: \r\n* Active peptic ulcer\r\n* Known endoluminal metastatic lesion(s) with history of bleeding\r\n* Inflammatory bowel disease (e.g. ulcerative colitis, Crohn’s disease), or other gastrointestinal conditions with increased risk of perforation
No evidence of active bleeding, bleeding diathesis, or hemoptysis (>= 1/2 teaspoon of red blood) within 8 weeks prior to registration
Bleeding esophageal or gastric varices within 30 days prior to treatment initiation
History of bleeding diathesis
Any active uncontrolled bleeding and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)
Previous major bleed (bleeding requiring transfusion of red blood cells) on LMWH
Patients must not have any evidence of bleeding diathesis or active gastrointestinal bleeding
Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)
Evidence of active bleeding or bleeding diathesis
History of significant bleeding disorder unrelated to cancer, including: congenital bleeding disorders (e.g, von Willebrand's disease), acquired bleeding disorder within the past 12 months (e.g, acquired anti-factor VIII antibodies, including any ongoing or recent less than or equal to 3 months), significant gastrointestinal bleeding, or use of oral anticoagulant therapy
History of bleeding diathesis or extensive bleeding requiring blood transfusion within 14 days of enrollment
History of significant congenital or acquired bleeding disorder unrelated to cancer
Vaginal bleeding of unknown etiology within 12 months of study entry
Patient must not have evidence of active bleeding or bleeding diathesis
Known presence of a significant congenital or acquired bleeding disorder unrelated to cancer
History of major hemorrhage including gastrointestinal bleeding (grade 2-4), pulmonary hemorrhage, or clinically significant hemoptysis (> 1 teaspoon [tsp] in 24 hours) within the last 5 years; patients with underlying conditions that predispose to bleeding, such as bleeding diathesis, known esophageal varices, or tumor involving major vessels, are also excluded
Patients who have a history of bleeding disorders including congenital or acquired coagulopathies
History of significant bleeding disorder unrelated to cancer, including:\r\n* Diagnosed congenital bleeding disorders (e.g., von Willebrand’s disease)\r\n* Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)\r\n* Ongoing or recent (=< 3 months) significant gastrointestinal bleeding
Active uncontrolled bleeding
Bleeding\r\n* Clinically significant bleeding, such as gross hematuria, gastrointestinal bleeding (excluding bleeding from rectal tumor), and hemoptysis within the 12 months before screening; if clinically significant bleeding has occurred within 12 months of screening but the cause has been identified and adequately treated (e.g., cystitis, ulcer), then this exclusion criterion does not apply\r\n* Minor biopsy-related bleeding lasting < 24 hours and resolved at least 1 week before Study Day 1 is allowed
Contraindications to seed placement, including uncontrollable bleeding diathesis
Evidence of active bleeding or bleeding diathesis
Patients with an active, bleeding diathesis
Evidence of active bleeding or bleeding diathesis
Significant history of bleeding events or pre-existing bleeding diathesis, within 6 months of randomization (unless the source of bleeding has been resected)
Uncontrolled severe bleeding tendency or active GI bleeding
Active bleeding or bleeding susceptibility
Evidence of active bleeding or bleeding diathesis
Evidence of active bleeding or bleeding diathesis
Active bleeding or a pathological condition that is associated with a high risk of bleeding
History of significant congenital or acquired bleeding disorder unrelated to cancer
Evidence of active bleeding or bleeding diathesis
Serious bleeding diathesis or those who are on therapeutic anticoagulation
Evidence or history of bleeding diathesis; any hemorrhage or bleeding event >= grade 4 within 4 weeks of start of FOLFIRI
Previous history of primary platelet disorder or bleeding disorder
Clinically significant bleeding within 4 weeks of screening defined as any grade 3 or grade 4 bleeding by WHO Bleeding Scale or any gastrointestinal (GI) bleeding or intracranial hemorrhage
Have a significant bleeding disorder unrelated to CML or Ph+ALL
Evidence of active bleeding or bleeding diathesis
EXPANSION COHORT ONLY: Evidence of active bleeding or bleeding diathesis
EXPANSION COHORT ONLY: Clinically significant gastrointestinal abnormalities that may increase the risk for GI bleeding including, but not limited to:\r\n* Activepeptic ulcer disease\r\n* Known intraluminal metastatic lesion/s with suspected bleeding\r\n* Inflammatory bowel disease \r\n* Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation
Known history of bleeding disorders (e.g., von Willebrand disease or hemophilia).
Clinically significant bleeding such as gross hematuria, gastrointestinal bleeding and hemoptysis within 6 months prior to enrollment.
Known bleeding diathesis (e.g., von Willebrand's disease) or hemophilia
Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy (in the absence of therapeutic anticoagulation), or tumor involving major vessels.
Contraindication to antiangiogenic agents, including: \r\n* Pulmonary hemorrhage/bleeding event >= grade 2 within 4 weeks of first dose of study drug\r\n* Any other hemorrhage/bleeding event >= grade 3 within 4 weeks of first dose of study treatment\r\n* Serious non-healing wound, ulcer, or bone fracture
Patients with active bleeding, including hemoptysis within 4 weeks of enrollment should be excluded, as there is no safety data with vorinostat in this setting
Known bleeding diathesis
History of severe gastrointestinal bleeding within 6 months; patients with gastrointestinal blood loss due to KS may be included
Patients must not have any evidence of bleeding diathesis
Bleeding disorder
History of underlying bleeding disorder, such as hemophilia
History of gastro-intestinal bleeding within 12 months
Recent history (within 1 year of first dose) of underlying, predisposing condition of bleeding or currently exhibits signs of bleeding
History of significant bleeding disorder unrelated to cancer, including: · Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease) · Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
Subject has history of gastrointestinal ulcer or gastrointestinal bleeding within 3 months prior to the planned first dose of study drug.
Known systemic bleeding or platelet disorder
Ongoing risk of bleeding due to active peptic ulcer disease, bleeding diathesis, or requirement for systemic anticoagulants. Use of heparin or thrombolytic agents for local maintenance or clearance of a central venous catheter is permitted.
Suffering from a known bleeding disorder.
Significant risk for bleeding due to active peptic ulcer disease or bleeding diathesis or requirement for systemic anticoagulation or history of significant gastrointestinal, urological, intracranial or other significant bleeding within 1 year from the start of treatment;
For subjects with known or suspected cirrhosis, esophagogastroduodenoscopy ) within 12 months of signing the informed consent form, showing no evidence of untreated varices or stigmata of active bleeding (such as active ulcer, visible vessel, or blood) is required. Subjects with history of upper GI bleeding must have an EGD of 3 months or less prior to signing the consent form confirming adequate prior endoscopic therapy (eg, no evidence of any untreated varices, recent or active bleeding, stigmata suggesting high risk for bleeding, active ulcer). Subjects with history/suspected esophageal varices must be on optimal medical management (eg, proton pump inhibitor and non-selective beta-blocker) per local institutional policy.
Subjects with current/a history of bleeding disorder or coagulopathy or who are at particularly high risk for bleeding complications.
History of upper gastrointestinal bleeding, ulceration, or perforation within 12 months prior to the first dose of study drug.
Subject has active gastrointestinal ulcer or gastrointestinal bleeding within 3 months prior to the planned first dose of study drug.
History of upper gastrointestinal bleeding, ulceration, or perforation within 6 months prior to the first dose of protocol therapy
Known congenital bleeding disorders such as hemophilia
No history of major bleeding, recent or active myocardial ischemia, gastrointestinal (GI) perforation, cerebrovascular accidents or other significant illness
Subject has a history of gastrointestinal bleeding within 90 days prior to the first dose of study drug.
Subjects who have a history of, or current evidence of bleeding disorder, i.e. any hemorrhage / bleeding event of CTCAE Grade >= 2 <4 weeks before the first dose of study drug.
Known inherited predisposition to bleeding or thrombosis
Ongoing risk of bleeding.
Evidence or history of bleeding diathesis. Any hemorrhage/bleeding event ? CTCAE (Common terminology criteria for adverse events) Grade 3 within 4 weeks of first dose of study drug
Active bleeding disorders or clinical signs of bleeding (Grade ?2).
Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia.
History of significant congenital or acquired bleeding disorder unrelated to cancer
Active bleeding within 4 weeks prior to screening visit
No major surgery within 4 weeks prior to enrollment or history of gastrointestinal bleeding within 3 months prior to enrollment; no signs or symptoms of active bleeding or non-healing ulcer will be permitted at study entry; patients with central pulmonary tumors with evidence of bronchial invasion, or presenting with hemoptysis will be excluded
Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)
Any hemorrhage or bleeding event
Active bleeding diathesis or history of any major bleeding (eg, requiring transfusion of red blood cells (RBCs), central nervous system (CNS) bleeding, or significant hemoptysis within 6 months of enrollment. Subjects with bleeding secondary to underlying disease (including gastrointestinal (GI) perforation or fistula) that has been corrected by surgery or alternative procedure may be included.
Patients taking anticoagulants or with a history of a bleeding diathesis
Evidence of active bleeding or bleeding diathesis
Active bleeding that requires hospitalization during the screening period
History of medically significant thromboembolic events or bleeding diathesis within the past 6 months
Evidence of active bleeding or bleeding diathesis; any medical condition requiring systemic anticoagulation (including anti-platelet agents)
Have evidence or history of any bleeding diathesis (including mild hemophilia), irrespective of severity.
Active GI bleeding and any bleeding diathesis or coagulopathy that is not correctable by usual therapy or hemostatic agents
3. History of upper GI bleeding, ulceration, or perforation within 12 months prior to the first dose of study drug.
History of upper gastrointestinal bleeding, ulceration, or perforation within 12 months.
Evidence of a bleeding diathesis that cannot be corrected with standard therapy or factor replacement
Evidence of active bleeding or bleeding diathesis.
History of perforation or bleeding related to peptic ulcer disease
History of unexplained bleeding episodes within 3 months of M402 dosing
Current (significant or uncontrolled) gastrointestinal bleeding
Prior treatment with a BTK inhibitor 19. Presence of transfusion-dependent thrombocytopenia or a history of bleeding disorders or clinical conditions (eg, gastrointestinal bleeding or constitutional disorders) that may increase risk of life-threatening bleeding when thrombocytopenic 20. History of stroke or intracranial hemorrhage within 6 months prior to signing the ICD 21. Medications that are strong inhibitors or inducers of CYP3A4/5 (eg, itraconazole, ketoconazole, clarithromycin, ritonavir, phenytoin, pentobarbital, and rifampin) should be changed; subjects who cannot change these medications must be excluded.
Patients with an active, bleeding diathesis
Evidence or history of any bleeding or coagulation disorder
Recent hemoptysis >2.5 mL or serious bleeding from another site, known bleeding disorder or coagulopathy or therapeutic anti-coagulation
Have significant bleeding disorders, vasculitis, or had a significant bleeding episode from the gastrointestinal (GI) tract within 3 months prior to receiving study drugs.
Active bleeding or high risk for bleeding contraindicating treatment with LMWH or edoxaban;
History of gastrointestinal bleeding within the past 6 months
History of bleeding diathesis or known qualitative platelet defect (including von Willebrand disease)
Esophageal variceal bleeding within 2 weeks prior to the first dose of TKM-080301.
Known bleeding diathesis or hemophilia
History of upper gastrointestinal ulceration, upper gastrointestinal bleeding, or upper gastrointestinal perforation within the past 3 years; patients with ulceration, bleeding or perforation in the lower bowel are not excluded
History of bleeding diasthesis
Participants with history of clinically significant bleeding, specifically any history of intracranial hemorrhage/hemorrhagic cardiovascular accident (CVA), or participants with gastrointestinal bleeding within the 12 months prior to study entry
Bleeding esophageal or gastric varices within 2 months before enrollment.
Ongoing major bleeding,
Patients with coagulation problems and active bleeding in the last month (peptic ulcer, epistaxis, spontaneous bleeding)
Active bleeding; pathological condition that carries a high risk of bleeding; risk of pseudoaneurysm of the internal carotid artery and carotid blowout syndrome.
Known bleeding disorders (e.g., von Willebrand’s disease) or hemophilia
Active bleeding disorders or evidence of evidence of chronic or acute disseminated intravascular coagulation (DIC)
Patients with known bleeding diathesis or prothrombin time (PT) or aPTT >1.5 x ULN or fibrinogen <0.5 x LLN
Uncontrolled peptic or gastric ulcer disease, or gastrointestinal bleeding within prior 6 months
Esophageal or gastric variceal bleeding within last 3 months
Known active gastrointestinal (GI) bleeding.
Known bleeding diathesis Known history of hereditary hemorrhagic telangiectasia (HHT).
Endometrial bleeding
Known history of bleeding disorders, eg, von Willebrand disease or hemophilia
Clinically significant bleeding such as gross hematuria, GI bleeding, and hemoptysis within the 6 months before screening
Does the subject have any bleeding diathesis, or must the subject take any anticoagulants, or antiplatelet agents, including NSAIDs that cannot be stopped for surgery?
Patients are excluded with history of recent < 6 months thromboembolic events, clinically significant bleeding—gross hematuria, hemoptysis, or gastrointestinal bleeding, history of bleeding diathesis or hypercoagulable state, or prior exposure to chimeric antibodies
Active bleeding
Known inherited predisposition to bleeding or thrombosis
Evidence or history of bleeding disorder, i.e. any hemorrhage / bleeding event of > Grade 2 within 4 weeks prior to the first dose of study drug
Subjects with evidence or history of bleeding diathesis; any hemorrhage or bleeding event NCI-CTCAE Grade ? 3 or higher within 4 weeks of start of investigational treatment
Patients with an underlying diagnosis or disease state associated with an increased risk of bleeding.
PART I: History of bleeding disorder
PART II: History of bleeding disorder
Patient has an underlying, predisposing condition of bleeding or currently exhibits signs of bleeding; the subject has a recent history of non-chemotherapy induced thrombocytopenic associated bleeding within 1 year prior to the first dose of study drug
Active, bleeding diathesis.
Patients with a history of/or active bleeding disorders
A target bleeding site can be identified.
Target bleeding site has moderate bleeding according to the Investigator's judgment.
A target bleeding site cannot be identified.
The target bleeding site has a mild or severe bleeding.
Uncorrected bleeding disorder.
If receiving warfarin: INR ? 3.0 (and no active bleeding, [i.e., no bleeding within 14 days prior to first dose of study therapy])
Known bleeding diathesis.
No known bleeding disorders
No active bleeding
No active bleeding
Active bleeding or high risk of bleeding
Active gastrointestinal bleeding
History of significant bleeding disorder unrelated to cancer, including:
Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies) of Screening visit
History of GI bleeding within 6 months of Screening visit
Evidence or history of bleeding diathesis (greater than normal risk of bleeding, i.e., hereditary hemorrhagic telangiectasia type I or HHT-1) or coagulopathy in the absence of therapeutic anti-coagulation or any hemorrhage/bleeding event > grade 3 within 4 weeks prior to registration; note: patients with full-dose anticoagulants are eligible provided the patient has been on a stable dose for at least 2 weeks of low molecular weight heparin; therapeutic Coumadin and aspirin doses > 325 mg daily are not allowed
For patients undergoing serial tumor biopsies, known bleeding diathesis or history of abnormal bleeding or require anti-coagulation therapy.
No history of bleeding diathesis.
Any hemorrhage or bleeding event >= grade 3 within 4 weeks prior to registration
Active bleeding
Patients with an active, bleeding diathesis
No gastrointestinal bleeding within 1 year of study entry.
Known bleeding diathesis, esophageal varices, or angioplasty
History of bleeding diathesis
History of significant bleeding disorder unrelated to cancer, including: diagnosed congenital bleeding disorders (e.g., von Willebrand’s disease), diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
History or evidence of inherited bleeding diathesis or coagulopathy with a risk of bleeding and active gastrointestinal bleeding
Patients with clinical bleeding, active gastric, or duodenal ulcer
Evidence of active bleeding or bleeding diathesis.
No bleeding diathesis
Patients with a history of familial bleeding disorders
Patients must not have any evidence of bleeding diathesis or signs of active bleeding
Clinically significant gastrointestinal bleeding (bleeding requiring procedural intervention, eg. variceal banding, transjugular intrahepatic portosystemic shunt (TIPS) procedure, arterial embolization, topical coagulation therapy) within 6 months prior to first dose.
History of bleeding diathesis
Known bleeding diathesis
Patients with evidence of a bleeding diathesis that cannot be corrected with standard therapy or factor replacement
Has a history of uncontrolled hereditary or acquired bleeding or thrombotic disorders
Has experienced a Grade ? 3 bleeding event within 3 months prior to randomization
Patients with an active, bleeding diathesis
Experienced any serious Grade 3-4 gastrointestinal bleeding within 3 months prior to study entry
for intratumoral cohort, bleeding diathesis or use of anticoagulants/antiplatelet agents that cannot be stopped
Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels by imaging, regardless of whether any chance of requiring vascular reconstruction
Evidence of active bleeding or bleeding diathesis
Patients with an active, bleeding diathesis
Patients with an active, bleeding diathesis
History of major thrombotic or clinically relevant major bleeding event in the past 6 months
Evidence of active bleeding, a bleeding diathesis or prothrombin time (PT) international normalized ratio (INR) > 1.5
Bleeding diathesis, resulting in symptomatic bleeding.
History of bleeding disorders
History of significant bleeding disorder unrelated to cancer, including:\r\n* Diagnosed congenital bleeding disorders (e.g., von Willebrand’s disease)\r\n* Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
Subject has history of gastrointestinal ulcer or gastrointestinal bleeding within 3 months prior to the first dose of study drug.
Active bleeding
Active bleeding that requires hospitalization during the screening period
Patients with coagulation problems and active bleeding in the last month (peptic ulcer, epistaxis, spontaneous bleeding)
Evidence of active bleeding or pathologic conditions that carry high risk of bleeding such as known bleeding disorders, coagulopathy or tumor involving major vessels
Evidence of active bleeding or bleeding diathesis
No clinically significant gastrointestinal abnormalities that may increase the risk of gastrointestinal bleeding within 28 days prior to registration including, but not limited to:\r\n* Active peptic ulcer\r\n* Known endoluminal metastatic lesion(s) with history of bleeding\r\n* Active inflammatory bowel disease (e.g. ulcerative colitis, Crohn’s Disease), or other gastrointestinal conditions with increased risk of perforation
No evidence of active bleeding, bleeding diathesis, or hemoptysis (>= ½ teaspoon of red blood) within 8 weeks of registration
No known bleeding diathesis
No central lung metastases with excessive active bleeding
Inherited predisposition to bleeding or thrombosis
History of bleeding disorders or thrombotic events, e.g. hemorrhagic or thrombotic events within 12 months, clinically significant or tumor-related hemoptysis, active gastrointestinal bleeding or ulcers or major injuries or surgery
Known predisposition to bleeding
Subject has ? grade 2 bleeding at the time of randomization
Subject with known congenital bleeding disorders or platelet dysfunction
Active grade >= 2 bleeding at the time of randomization, including hematuria
History of grade 4 bleeding
Patients at risk of non-disease related major bleeding (eg, recent GI hemorrhage or neurosurgery, within previous 21 days).
History of known bleeding disorder (i.e. disseminated intravascular coagulation or clotting factor deficiency);
No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices) within 14 days prior to registration
No clinical signs active of bleeding
Patients with overt bleeding
Known bleeding disorders
Known bleeding disorder per patient reported history
Known bleeding or thrombotic diathesis
Active bleeding or high risk of bleeding in the opinion of the investigator
Bleeding diathesis or inability to hold anticoagulation for surgery
Persistent oral bleeding: > 15 mL (estimated) per day
Active bleeding (grade 2 or higher) at the time of enrollment
History of intracranial bleeding at any time
Active bleeding
Any of the following conditions:\r\n* Intracranial bleeding =< 6 months prior to randomization\r\n* Intraocular bleeding =< 6 months prior to randomization\r\n* Gastrointestinal bleeding and/or endoscopically proven ulcer =< 6 months prior to randomization\r\n* Head trauma or major trauma =<1 month prior to randomization\r\n* Neurosurgery =< 2 weeks prior to randomization\r\n* Major surgery =< 1 week prior to randomization\r\n* Overt major bleeding at the time of randomization\r\n* Gross hematuria at the time of randomization
Participants with untreated or incompletely treated varices with bleeding or high-risk for bleeding
Known bleeding disorders (eg, von Willebrand’s disease or hemophilia), active bleeding disorders or clinical signs of bleeding (grade >= 2)
Known bleeding disorders (e.g., von Willebrand’s disease) or hemophilia
Has known bleeding diathesis that would be a safety risk;
Any bleeding episode considered life-threatening, or any Grade 3 or 4 gastrointestinal bleeding episode in the 3 months prior to randomization requiring intervention.
Esophageal or gastric varices that require intervention or represent high bleeding risk. Participants with evidence of portal hypertension or prior bleeding must have had endoscopic evaluation within 3 months prior to randomization.
Uncontrolled hereditary or acquired thrombotic or bleeding disorder.
History of major bleeding (requiring a blood transfusion ? 2 units) not related to a tumor within the past 12 months
Patient has a known bleeding diathesis (e.g. von Willebrand’s disease) or hemophilia
Active or serious bleeding within two weeks of enrollment
Active bleeding diathesis
Patients must not have a severe bleeding disorder
Recent acute bleeding requiring intervention in less than 24 hours
Patients will also be excluded if they have active bleeding, acute thrombosis, ischemia, hemodynamically unstable, and uncontrolled pain
Congenital bleeding disorder or predisposition to priapism that is contraindicative to vacuum constriction\r\ndevices (VCD) use
Non-correctable bleeding diathesis
The subject has a history of significant bleeding disorders
Active major bleeding
Active bleeding or high risk for bleeding (e.g. known acute gastrointestinal ulcer)
Familial bleeding diathesis
Gastrointestinal bleeding; note that the presence of any symptoms (dyspnea, fatigue, angina, weakness, malaise, melena, hematochezia, hematemesis, anemia, abdominal pain) will require clinical assessment to rule out gastrointestinal bleeding
Patients on anticoagulation or with bleeding disorders should be evaluated by a physician for risk/benefit of bleeding disorders with intramuscular injections prior to study enrollment; patients determined to be at high risk for bleeding with intramuscular injections will be excluded
Women with active liver disease, abnormal uterine bleeding, or prior diagnosis of endometrial hyperplasia
History of gastric ulcer within the past 5 years (with or without bleeding)
History of bleeding disorder or hemorrhagic stroke
Active bleeding or otherwise considered high risk for hemorrhage (e.g. known acute gastrointestinal ulcer)
Known bleeding diathesis
EXCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT): Known bleeding disorders (eg, von Willebrand’s disease) or hemophilia
Grade 3 or higher recent (within the past 6 months) or ongoing bleeding events
History of aspirin intolerance, bleeding diathesis, peptic ulcer or gastrointestinal bleed, endoscopic complications, or contraindication to colonoscopy
Active bleeding condition (not limited to: thrombocytopenia, hemophilias, potential bleeding lesions, recent trauma or surgery, recent stroke, confirmed intracranial or intraspinal bleeding)
History of a bleeding diathesis or current anticoagulant therapy
Bleeding diathesis
Bleeding diathesis, hemorrhagic lesions, active bleeding, and other conditions with a high risk for bleeding
History of a bleeding tendency or current use of Coumadin or other anticoagulants
Known bleeding disorders that preclude intramuscular injection (e.g., on anticoagulants or thrombocytopenia)
History of endoscopically or radiographically diagnosed peptic ulcer disease with upper GI bleeding during the past 5 years or history of endoscopically or radiographically diagnosed peptic ulcer disease with upper GI bleeding any time while taking aspirin
Evidence of active mucosal or internal bleeding
Clinically apparent bleeding diathesis (meaning bleeding that is spontaneous, excessive, or delayed in onset following tissue injury results from a localized pathologic process or a disorder of the hemostatic process, involving a complex interplay among vascular integrity, platelet number and function, coagulation factors, and fibrinolysis)
History of gastric ulcer within the past 5 years (with or without bleeding)
History of bleeding disorder or hemorrhagic stroke
active, bleeding diathesis;
History of bleeding/coagulation problems
active bleeding or at high risk of bleeding
The patient has a lack of bleeding disorders, and
Bleeding disorder
Patients with or with a history of uncontrolled bleeding diathesis
No history of bleeding diathesis
History of major bleeding with bronchoscopy
Major surgery or significant bleeding episodes within 28 days before study initiation\r\n* Major surgery does not include: breast or other biopsies obtained for diagnosis, placement of radio-opaque clip to localize a tumor or tumors for subsequent surgical resection, placement of central venous access, pretreatment lymph node sampling\r\n* Significant bleeding episodes are defined for the purpose of this study as hemoptysis or upper/lower gastrointestinal bleeding\r\n* Although bevacizumab will be administered in tracer quantities in this study and is not expected to have pharmacologic effects, participants with major surgery or significant bleeding episodes within 28 days before study initiation may be at a higher risk of bleeding
Patient must not have evidence of active bleeding or bleeding diathesis
Active vaginal bleeding requiring packing and emergent radiation therapy
Participants must lack bleeding disorders, and be able to provide informed consent; the latter two criteria will be assessed from the patient’s history and the consenting interview
Lack bleeding disorders
Known inherited or acquired bleeding disorders.
Known bleeding disorders (e.g., von Willebrand’s disease) or hemophilia
Evidence of mucosal or internal bleeding and/or is platelet transfusion refractory
Known bleeding disorder that cannot be sufficiently corrected with co-fact or fresh frozen plasma (FFP)
Acute gastrointestinal (GI) bleeding
Bleeding disorders
Any condition resulting in increased risk of bleeding at biopsy.
History of any coagulation, bleeding, or blood disorders (e.g. anemia)
No known bleeding disorders
No active bleeding
No active bleeding in the post-operative period
Active bleeding or high risk of bleeding
History or presence of significant bleeding disorders
Known bleeding diathesis or history of abnormal bleeding, or any other known coagulation abnormalities that would contraindicate the tumor biopsy procedure.
Bleeding and Thrombosis:
If active bleeding requiring acute surgical intervention, not eligible
History of significant bleeding disorder unrelated to CML
The patient has uncontrolled or severe coagulopathies or a history of clinically significant bleeding within the past 6 months, such as hemoptysis, epistaxis, hematochezia, hematuria, or gastrointestinal bleeding.
The patient has a known predisposition for bleeding such as von Willebrand's disease or other such condition.
Known presence of significant congenital or acquired bleeding disorder unrelated to cancer
Mucosal or internal bleeding, or platelet transfusion refractory
Known bleeding diathesis or history of abnormal bleeding, or any other known coagulation abnormalities that would contraindicate the tumor biopsy procedure.
Bleeding or thrombotic disorders.
Active bleeding or pathologic condition that carries a high risk of bleeding
Tumors located in the central chest or other location where bleeding is associated with high morbidity