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 surgeryXx_NEWLINE_xXThe patient has experienced any grade 3-4 gastrointestinal bleeding within 3 months prior to randomizationXx_NEWLINE_xXActive 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 eligibleXx_NEWLINE_xXNo history of gastrointestinal bleeding (GI) bleeding requiring a blood transfusion, endoscopic or operative interventionXx_NEWLINE_xXPatients with intestinal obstruction or gastrointestinal bleedingXx_NEWLINE_xXPatients 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)Xx_NEWLINE_xXPatients with evidence of active septicemia, severe infection, gastrointestinal bleeding or severe gastrointestinal symptoms requiring medical or surgical therapyXx_NEWLINE_xXPatients 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 hemorrhagesXx_NEWLINE_xXActive bleeding or pathologic condition that carries a high risk of bleeding. No bleeding diathesis.Xx_NEWLINE_xXHistory of bleeding esophageal varices in previous 6 months, which have not been adequately managed with banding or sclerotherapy.Xx_NEWLINE_xXActive uncontrolled bleedingXx_NEWLINE_xXClinically significant bleeding event within the last 3 months, unrelated to trauma, or underlying condition that would be expected to result in a bleeding diathesis.Xx_NEWLINE_xXEvidence of active bleeding or bleeding diathesis; recent hemoptysis (>= 1/2 teaspoon of red blood within 8 weeks before first dose of study drug)Xx_NEWLINE_xXEvidence of active bleeding or bleeding diathesis; recent hemoptysis (>= ½ teaspoon of red blood within 8 weeks before first dose of study drug)Xx_NEWLINE_xXPatients with an active, bleeding diathesisXx_NEWLINE_xXSignificant bleeding disorder;Xx_NEWLINE_xXPatients with a history of bleeding diathesis are ineligibleXx_NEWLINE_xXEvidence of mucosal or internal bleeding or platelet transfusion refractoryXx_NEWLINE_xXPatients with known involvement of the CNS by malignancy will be included if there is no evidence of active bleeding or intratumoral hemorrhage on radiographic imagingXx_NEWLINE_xXAny history of hereditary bleeding disordersXx_NEWLINE_xXHistory of bleeding diathesis or clinically significant bleeding within 14 days prior to randomization.Xx_NEWLINE_xXActive bleeding diatheses.Xx_NEWLINE_xXClinically significant gastrointestinal bleeding within 6 months prior to the first dose of ALRN-6924Xx_NEWLINE_xXHistory of hemolytic anemia or bleeding diathesisXx_NEWLINE_xXPatients with any grade 3-4 gastrointestinal bleeding within 3 months prior to enrollmentXx_NEWLINE_xXSignificant GI or variceal bleeding or subdural hematoma within 3 months of the first dose of study drugXx_NEWLINE_xXAny hemorrhage or bleeding event >= NCI CTCAE v4.0 grade 3 within 4 weeks prior to study registrationXx_NEWLINE_xXVariceal bleeding within 1 month prior to study registrationXx_NEWLINE_xXPatients with an active, bleeding diathesisXx_NEWLINE_xXActive gastrointestinal bleedingXx_NEWLINE_xXActive bleeding disorder in the past 6 months.Xx_NEWLINE_xXPHASE II: History of bleeding diathesis; patients receiving anti-coagulation must be able safely interrupt treatment for tumor biopsyXx_NEWLINE_xXKnown hemorrhagic diathesis or active bleeding disorderXx_NEWLINE_xXHistory of a bleeding disorderXx_NEWLINE_xXSignificant bleeding disorders.Xx_NEWLINE_xXPatients with evidence of significant mucosal or internal bleedingXx_NEWLINE_xXNo 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 weeksXx_NEWLINE_xXSubjects 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.Xx_NEWLINE_xXHistory of bleeding disorders or thromboembolic events in prior 3 monthsXx_NEWLINE_xXSubject has an underlying condition predisposing them to bleeding or currently exhibits signs of clinically significant bleedingXx_NEWLINE_xXSubject has a recent history of non-chemotherapy-induced thrombocytopenic-associated bleeding within 1 year prior to the first dose of study drugXx_NEWLINE_xXSubjects may not have a history of bleeding diathesis or abnormal sensitivity to ionizing radiationXx_NEWLINE_xXSignificant 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)Xx_NEWLINE_xXHistory of significant bleeding disorder unrelated to cancerXx_NEWLINE_xXPatients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vesselsXx_NEWLINE_xXPatients with an active, bleeding diathesis or on oral anti-vitamin K medication (except low dose coumarin)Xx_NEWLINE_xXActive bleeding conditionsXx_NEWLINE_xXActive or prior documented GI bleeding (eg, esophageal varices or ulcer bleeding) within 12 monthsXx_NEWLINE_xXOngoing risk for bleeding due to active peptic ulcer disease or bleeding diathesis.Xx_NEWLINE_xXIf receiving warfarin: INR ? 3.0 and no active bleeding (i.e., no bleeding within 14 days prior to first dose of study therapy).Xx_NEWLINE_xXClinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drugXx_NEWLINE_xXAny grade 3-4 gastrointestinal (GI) bleeding within 3 months prior to enrollmentXx_NEWLINE_xXhistory of bleeding disorderXx_NEWLINE_xXVascular abnormalities or bleeding diathesis that indicates hepatic artery catheterization is contraindicatedXx_NEWLINE_xXHistory 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).Xx_NEWLINE_xXKnown varices at risk of bleeding, including medium or large esophageal or gastric varices, or active peptic ulcer.Xx_NEWLINE_xXOngoing, clinically significant bleeding (CTCAE grade 3 or 4)Xx_NEWLINE_xXBleeding 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 tumorsXx_NEWLINE_xXSignificant recent bleeding history defined as NCI CTCAE grade ?2 within the last 3 months, unless precipitated by an inciting event (e.g., surgery, trauma, injury)Xx_NEWLINE_xXKnown bleeding disorders (e.g., von Willebrand’s disease) or hemophiliaXx_NEWLINE_xXHistory 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)Xx_NEWLINE_xXHistory of upper GI bleeding, ulceration or perforation within 6 months before the first dose of defactinib.Xx_NEWLINE_xXOngoing risk for bleeding due to active peptic ulcer disease, bleeding diathesis or requirement for systemic anticoagulationXx_NEWLINE_xXAny grade >/=3 hemorrhage or bleeding event within 4 weeks prior to initiation of study treatmentXx_NEWLINE_xXPatients 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 eligibleXx_NEWLINE_xXKnown bleeding disorders (e.g., von Willebrand’s disease) or hemophiliaXx_NEWLINE_xXParticipants with inherited or acquired bleeding disordersXx_NEWLINE_xXPatients with uncontrolled coagulopathies who are at increased risk of bleeding.Xx_NEWLINE_xXThe 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.Xx_NEWLINE_xXThe patient has a known predisposition for bleeding such as von Willebrand's disease or other such condition.Xx_NEWLINE_xXAny hemorrhage or bleeding event ? grade 3 within 4 weeks.Xx_NEWLINE_xXRecent or active bleeding diathesis or arterial vascular event within 4 weeksXx_NEWLINE_xXAny hemorrhage or bleeding event >= NCI CTCAE grade 3 within 4 weeks prior to start of study medicationXx_NEWLINE_xXAny hemorrhage or bleeding event >= NCI CTCAE grade 3 within 4 weeks prior to start of study medicationXx_NEWLINE_xXSubject in whom the bleeding flux from the identified lesion is > 0.000040[g/(cm²•s)] and ?0.013[g/(cm²•s)].Xx_NEWLINE_xXKnown bleeding diathesis (eg, von Willebrand’s disease) or hemophiliaXx_NEWLINE_xXPersonal history of endometrial cancer or any abnormal uterine bleedingXx_NEWLINE_xXMajor bronchial occlusion or bleeding not amenable to palliationXx_NEWLINE_xXPatients with an active bleeding diathesisXx_NEWLINE_xXPatients 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.Xx_NEWLINE_xXHistory of major gastrointestinal bleeding within the last 3 months or any evidence of active gastrointestinal bleeding excludes the subject.Xx_NEWLINE_xXHistory 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 bleedingXx_NEWLINE_xXEvidence of active bleeding or bleeding disorderXx_NEWLINE_xXIf they have had any active bleeding in the last =< 4 weeks or have an otherwise known bleeding diathesisXx_NEWLINE_xXCOHORT B, GROUP 6: HEPATOCELLULAR CARCINOMA: Variceal bleeding within last 6 monthsXx_NEWLINE_xXPresence of GI bleeding.Xx_NEWLINE_xXAdvanced primary with impeding occlusion, perforation or bleeding, dependent on transfusionXx_NEWLINE_xXAbnormal bleeding times or active anti-coagulation therapyXx_NEWLINE_xXKnown or suspected clinically significant active bleeding.Xx_NEWLINE_xXHistory of hemolytic anemia or bleeding diathesis or positive direct antiglobulin test.Xx_NEWLINE_xXRequires therapeutic anticoagulation or has known active bleeding diathesisXx_NEWLINE_xXActive gastrointestinal bleeding within previous 2 monthsXx_NEWLINE_xXActive uncontrolled bleeding or a known bleeding diathesisXx_NEWLINE_xXUncontrolled severe bleeding tendency or active gastrointestinal (GI) bleedingXx_NEWLINE_xXThe patient has any pre-existing coagulopathy, recent hemoptysis, gross hematuria, or gastrointestinal bleeding, and a history of a clinically significant cardiovascular or cerebrovascular event within 12 months prior to study entryXx_NEWLINE_xXHistory of active gastrointestinal bleeding within 6 months prior to randomization.Xx_NEWLINE_xXCRITERIA SPECIFIC FOR COHORT #2 (MCL): Known bleeding disorders (eg, von Willebrand's disease) or hemophiliaXx_NEWLINE_xXHistory of upper gastrointestinal (GI) bleeding from esophageal and/or gastric varices within 12 months before enrollmentXx_NEWLINE_xXSubject with any pulmonary hemorrhage/bleeding event of NCI-CTCAE v4.0 Grade 2 or higher within 6 months before first dose of study treatment any other hemorrhage/bleeding event of NCI-CTCAE v4.0 Grade 3 or higher within 6 months before first dose of study treatmentXx_NEWLINE_xXContraindication for ibrutinib use because of a bleeding diathesis.Xx_NEWLINE_xXSignificant risk for bleedingXx_NEWLINE_xXBleeding disorders or active significant bleeding (i.e. hemoptysis, hematochezia, hematemesis) within 3 weeksXx_NEWLINE_xXFor cohort 3, any major bronchial occlusion or bleeding not amenable to palliationXx_NEWLINE_xXFor 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 bleedingXx_NEWLINE_xXNormal coagulation profile and no history of substantial non-iatrogenic bleeding diathesisXx_NEWLINE_xXInability to tolerate aspirin, or other forms of anticoagulation, due to bleeding diathesisXx_NEWLINE_xXHistory 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 excludedXx_NEWLINE_xXPatients with higher risk of bleeding (deemed by the treating physician) or on anticoagulationXx_NEWLINE_xXHas history of known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhage within 12 months of start of study drugXx_NEWLINE_xXHospitalized patients (or willing to be hospitalized for 24 hours after Rx) with Modified WHO Grade 1 (subset) or Grade 2 Bleeding Score or at risk for same within 4 weeks of screening. The Grade 1 subset includes patients who have either epistaxis, hematuria, oral petechiae, or bleeding at invasive or other wound sites.Xx_NEWLINE_xXPatients with history of intra-abdominal bleeding or retroperitoneal bleeding within the last 3 years are excludedXx_NEWLINE_xXGI Bleeding (eg, esophageal varices or ulcer bleeding) within 12 monthsXx_NEWLINE_xXKnown bleeding disordersXx_NEWLINE_xXPatients with an underlying condition predisposing them to bleeding or currently exhibiting signs of clinically significant bleedingXx_NEWLINE_xXPatients with a recent history of non-chemotherapy-induced thrombocytopenic-associated bleeding within 1 year prior to the first dose of study drugXx_NEWLINE_xXKnown inherited predisposition to bleeding or thrombosisXx_NEWLINE_xXHistory of bleeding diathesisXx_NEWLINE_xXHistory 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 yearXx_NEWLINE_xXPatients with known bleeding disorders or more than punctate intratumoral hemorrhage are excludedXx_NEWLINE_xXGrade ? 3 hemorrhage or bleeding event within 28 days prior to initiation of study treatmentXx_NEWLINE_xXActive uncontrolled bleeding or a known bleeding diathesisXx_NEWLINE_xXThe 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)Xx_NEWLINE_xXSubjects 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 eligibleXx_NEWLINE_xXPatients must have normal coagulation profile and no history of substantial non-iatrogenic bleeding diathesis.Xx_NEWLINE_xXHistory 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.Xx_NEWLINE_xXActive bleeding or a pathological condition that is associated with a high risk of bleeding (therapeutic anticoagulation is allowed)Xx_NEWLINE_xXHistory 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).Xx_NEWLINE_xXPatients with major gastrointestinal bleeding in the prior 2 months of enrollment.Xx_NEWLINE_xXEvidence or history of bleeding disorder.Xx_NEWLINE_xXExisting bleeding or condition associated with increased risk of bleedingXx_NEWLINE_xXPatients with a history of bleeding disordersXx_NEWLINE_xXKnown bleeding disorders (e.g., von Willebrand’s disease or hemophilia)Xx_NEWLINE_xXPatients should not have transfusion-dependent thrombocytopenia or bleeding disordersXx_NEWLINE_xXActive bleeding or pathologic condition that carries a high risk of bleeding (e.g., hereditary hemorrhagic telangiectasia)Xx_NEWLINE_xXHistory 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 bleedingXx_NEWLINE_xXHistory 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).Xx_NEWLINE_xXFOR 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 medicationXx_NEWLINE_xXEvidence of active bleeding or bleeding diathesisXx_NEWLINE_xXAny hemorrhage or bleeding event >= NCI CTCAE grade 3 within 4 weeks prior to start of study medicationXx_NEWLINE_xXPatients on non-aspirin anti-coagulation (Coumadin, heparins, or clopidogrel) or with documented bleeding disorders will be excludedXx_NEWLINE_xXPlatelet 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 disorderXx_NEWLINE_xXKnown bleeding disorders (eg, von Willebrand’s disease) or hemophiliaXx_NEWLINE_xXPatients with evidence or history of bleeding diathesis; any hemorrhage or bleeding event >= CTCAE grade 3 within 4 weeks before the start of study treatmentXx_NEWLINE_xXKnown bleeding disorders (von Wilebrand’s disease or hemophilia)Xx_NEWLINE_xXUncontrolled 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 hemorrhageXx_NEWLINE_xXKnown predisposition for bleeding such as von Willebrand’s disease or other such condition(s)Xx_NEWLINE_xXPrior history of clinically significant bleeding, intestinal obstruction, or GI perforation within 6 months of initiation of study treatment.Xx_NEWLINE_xXClinically significant bleeding within two weeks prior to randomization (e.g., gastrointestinal (GI) bleeding, intracranial hemorrhage)Xx_NEWLINE_xXHas history of known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhage within 12 months of registrationXx_NEWLINE_xXHas history bleeding disorders (e.g., pulmonary hemorrhage, significant hemoptysis, menometrorrhagia not responding to hormonal treatment) ? 2 months before C1D1Xx_NEWLINE_xXHistory of hemoptysis or any significant bleeding within the last 1 month prior to enrollmentXx_NEWLINE_xXHistory of clinically significant bleeding or known platelet or coagulation disorderXx_NEWLINE_xXKnown bleeding disorders (e.g., von Willebrand’s disease) or hemophiliaXx_NEWLINE_xXHas an active bleeding disorders or evidence of chronic or acute disseminated intravascular coagulation (DIC)Xx_NEWLINE_xXHistory of significant congenital or acquired bleeding disorder unrelated to cancerXx_NEWLINE_xXGrade 3 gastrointestinal (GI) bleeding within 3 months prior to screeningXx_NEWLINE_xXKnown bleeding disordersXx_NEWLINE_xXKnown bleeding disorders (eg, von Willebrand’s disease) or hemophiliaXx_NEWLINE_xXKnown history of bleeding diathesisXx_NEWLINE_xXNeeding medical attention for serious bleeding in past 4 weeksXx_NEWLINE_xXPatients with an active bleeding diathesisXx_NEWLINE_xXPatients with a history of peptic ulcer disease or gastrointestinal bleedingXx_NEWLINE_xXPatients with any major bleeding current or within the past 4 weeks. (e.g. recent gastrointestinal [GI] hemorrhage or neurosurgery).Xx_NEWLINE_xXSubjects who had a prior intracranial hemorrhage, known arteriovenous malformation or aneurysm, head trauma, or evidence of active bleeding;Xx_NEWLINE_xXSubjects who within 21 days prior to randomization have had gastrointestinal or genitourinary bleeding;Xx_NEWLINE_xXKnown inherited predisposition to bleeding or thrombosisXx_NEWLINE_xXDocumented or known bleeding disorder.Xx_NEWLINE_xXKnown bleeding disorders (e.g., von Willebrand’s disease) or hemophiliaXx_NEWLINE_xXConcomitant use of warfarin or other vitamin K antagonists; Note: Subjects receiving antiplatelet agents in conjunction with ibrutinib should be observed closely for any signs of bleeding or bruising, and ibrutinib should be withheld in the event of any bleeding events; supplements such as fish oil and vitamin E preparations should be avoidedXx_NEWLINE_xXPatients with a history of gastrointestinal bleeding (GIB) within 6 weeks prior to registration are not eligibleXx_NEWLINE_xXEvidence 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 allowedXx_NEWLINE_xXPatients with an active bleeding diathesisXx_NEWLINE_xXHave a significant bleeding disorder or vasculitis or had a Grade ?3 bleeding episode within 12 weeks prior to enrollment.Xx_NEWLINE_xXSignificant 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 2Xx_NEWLINE_xXPatient on anticoagulation or with bleeding diathesis due to risk of hematomas at injection siteXx_NEWLINE_xXAny history of significant bleeding disorder unrelated to cancer, including any congenital bleeding disorder or any acquired bleeding disorder within one year of start of studyXx_NEWLINE_xXNo history of diagnosed congenital bleeding disorders (e.g., von Willebrand’s disease)Xx_NEWLINE_xXNo abnormalities no history of diagnosed acquired bleeding disorders within one year (e.g., acquired anti-factor VIII antibodies) of registration on protocol therapyXx_NEWLINE_xXNo abnormalities no history of ongoing or recent (less than or equal to 3 months of registration on protocol therapy) significant gastrointestinal bleedingXx_NEWLINE_xXKnown bleeding disorders (e.g., von Willebrand's disease) or hemophiliaXx_NEWLINE_xXKnown abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants precluding intramuscular injections of fulvestrant or goserelin (if applicable)Xx_NEWLINE_xXThe patient has significant bleeding disorders, vasculitis, or experienced grade 3/4 gastrointestinal (GI) bleeding within 3 months prior to enrollmentXx_NEWLINE_xXFor patients undergoing serial tumor biopsies, known bleeding diathesis or history of abnormal bleeding or require anti-coagulation therapy which cannot be interrupted for biopsyXx_NEWLINE_xXAny active bleeding in the last =< 4 weeks or have an otherwise known bleeding diathesisXx_NEWLINE_xXPatients 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)Xx_NEWLINE_xXNo active bleedingXx_NEWLINE_xXMajor bleeding in the last 4 weeks prior to study entryXx_NEWLINE_xXPHASE 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 surgeryXx_NEWLINE_xXHistory 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 allowedXx_NEWLINE_xXDocumented or known bleeding disorder.Xx_NEWLINE_xXHistory of clinically significant gastrointestinal bleeding, colitis, or gastrointestinal perforation.Xx_NEWLINE_xXPatients with evidence or history of bleeding diathesis; any hemorrhage or bleeding event >= CTCAE grade 3 within 4 weeks of start of study enrollmentXx_NEWLINE_xXKnown bleeding disorders (e.g., von Willebrand’s disease) or hemophiliaXx_NEWLINE_xXREGORAFENIB EXCLUSION CRITERIA: Any hemorrhage or bleeding event >= grade 3 within 4 weeks prior to start of regorafenibXx_NEWLINE_xXPatient has any bleeding diathesis, or must take anticoagulants or antiplatelet agents, including nonsteroidal anti inflammatory drugs, that cannot be stopped for biopsy or surgery.Xx_NEWLINE_xXMajor bleeding within the last 6 months.Xx_NEWLINE_xXSubjects with bleeding diatheses, thrombocytopenia or current anticoagulant useXx_NEWLINE_xXPatients on full-dose anticoagulation must be on a stable dose (minimum duration 14 days) of oral anticoagulant or low molecular weight heparin; if receiving warfarin, the patient must have an INR =< 3.0 and no active bleeding (that is, no bleeding within 14 days prior to first dose of protocol therapy) or pathological condition present that carries a high risk of bleeding (for example, tumor involving major vessels or known varices)Xx_NEWLINE_xXThe patient has experienced any grade 3-4 gastrointestinal (GI) bleeding within 3 months prior to enrollmentXx_NEWLINE_xXNo bleeding from gastrointestinal ulcers or other sites of bleedingXx_NEWLINE_xXAny hemorrhage or bleeding event ? NCI CTCAE Grade 3 within 4 weeks prior to study registrationXx_NEWLINE_xXFor 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 agentsXx_NEWLINE_xXMust not have any evidence of bleeding diathesis or active gastrointestinal bleedingXx_NEWLINE_xXPersonal or family history of bleeding diathesis and a coagulation profile that would preclude patient from undergoing a neurosurgical procedureXx_NEWLINE_xXPatients must not have had any active bleeding in the last =< 4 weeks or have an otherwise known bleeding diathesisXx_NEWLINE_xXPatients with active hemoptysis, clinically significant non hemorrhoidal gastrointestinal (GI) bleeding or those with bleeding diathesisXx_NEWLINE_xXHistory of symptomatic gastrointestinal disorder within the last five years resulting in bleeding or chronic or frequent diarrheaXx_NEWLINE_xXHistory of bleeding disorder or diathesisXx_NEWLINE_xXAny active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)Xx_NEWLINE_xXPresence of bleeding diathesisXx_NEWLINE_xXActive and significant bleedingXx_NEWLINE_xXGastrointestinal bleeding or active hemoptysis (bright red blood of at least half teaspoon) within 3 weeks prior to the first dose of study drug.Xx_NEWLINE_xXActive 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 eligibleXx_NEWLINE_xXPatients with evidence of recent intratumoral hemorrhage (within 3 months of study enrollment), gastrointestinal bleeding, history of coronary artery disease or on anticoagulation therapyXx_NEWLINE_xXEvidence of active bleeding or bleeding diathesisXx_NEWLINE_xXNo active uncontrolled bleeding/bleeding diathesisXx_NEWLINE_xXAny active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)Xx_NEWLINE_xXActive bleeding diathesis or history of major bleeding, central nervous system (CNS) bleeding, or significant hemoptysis within the past 6 monthsXx_NEWLINE_xXKnown inherited predisposition to bleeding or thrombosisXx_NEWLINE_xXPatients with history of clinically significant bleeding disorderXx_NEWLINE_xXAny active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)Xx_NEWLINE_xXEvidence of active bleeding or bleeding diathesisXx_NEWLINE_xXDocumented or known bleeding disorder.Xx_NEWLINE_xXAny active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)Xx_NEWLINE_xXPatients at risk for gastrointestinal bleeding (example: peptic ulcer disease, prolonged daily non-steroidal anti-inflammatory use)Xx_NEWLINE_xXActive gastrointestinal bleedingXx_NEWLINE_xXEvidence of uncontrollable bleeding diathesisXx_NEWLINE_xXSubject has an underlying condition predisposing them to bleeding or currently exhibits signs of clinically significant bleedingXx_NEWLINE_xXSubject has a recent history of non-chemotherapy-induced thrombocytopenic-associated bleeding within 1 year prior to the first dose of study drugXx_NEWLINE_xXHistory or presence of any significant bleeding disordersXx_NEWLINE_xXHistory 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)Xx_NEWLINE_xXAny active uncontrolled bleeding or bleeding diathesis (e.g., active peptic ulcer disease)Xx_NEWLINE_xXEvidence of bleeding diathesis or use of anticoagulant medication or any medication that may increase the risk of bleeding that cannot be stopped prior to surgeryXx_NEWLINE_xXAny active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)Xx_NEWLINE_xXPatients with evidence of active bleeding, intratumoral hemorrhage or history of bleeding diatheses, unless specifically occurring as an isolated incident during reversible chemotherapy-induced thrombocytopeniaXx_NEWLINE_xXHistory of significant bleeding disorder unrelated to cancerXx_NEWLINE_xXHistory 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 bleedingXx_NEWLINE_xXPatients with active bleeding or pathologic conditions that carry high risk of bleeding, such as a known bleeding disorder, coagulopathy, or tumor involving major vesselsXx_NEWLINE_xXEvidence of active bleeding or bleeding diathesisXx_NEWLINE_xXHistory 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)Xx_NEWLINE_xXClinically 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 bleedingXx_NEWLINE_xXAny other hemorrhage/bleeding event >= CTCAE grade 3 within 4 weeks of first dose of study drugXx_NEWLINE_xXHistory 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)Xx_NEWLINE_xXPatients 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).Xx_NEWLINE_xXKnown varices at risk of bleeding, including medium or large esophageal or gastric varices, or active peptic ulcer.Xx_NEWLINE_xXGrade 3 or higher bleeding event =< 3 months prior to randomizationXx_NEWLINE_xXKnown bleeding disorders (e.g., von Willebrand’s disease) or hemophiliaXx_NEWLINE_xXA history of variceal bleeding where the varices have not been eradicated or decompressed by shunt placementXx_NEWLINE_xXPatients with an active bleeding diathesisXx_NEWLINE_xXBleeding diathesis, not correctable by usual forms of therapyXx_NEWLINE_xXBleeding diathesis, not correctable by usual forms of therapyXx_NEWLINE_xXActive uncontrolled bleeding or a known bleeding diathesisXx_NEWLINE_xXHistory of significant bleeding disorder or uncontrolled seizuresXx_NEWLINE_xXClinical evidence of portal hypertension with bleeding esophageal or gastric varices at Screening, or within 6 months before randomizationXx_NEWLINE_xXAny hemorrhage / bleeding event ? CTCAE v.4.03 Grade 3 within 4 weeks before randomizationXx_NEWLINE_xXSubject has an underlying bleeding disorderXx_NEWLINE_xXActive bleeding diatheses which in the opinion of the treating physician poses a significantly increased operative risk.Xx_NEWLINE_xXindication for anticoagulant treatment for a disease other than the index VTE episode; Related to bleeding risk:Xx_NEWLINE_xXactive bleeding or a high risk of bleeding contraindicating anticoagulant treatment;Xx_NEWLINE_xXHave active uncontrolled bleeding or a known bleeding disorderXx_NEWLINE_xXPatients with coagulation problems and active bleeding in the last month prior to cycle 1 day 1 (peptic ulcer, epistaxis, spontaneous bleeding)Xx_NEWLINE_xXClinically significant bleeding event within the last 3 months, unrelated to trauma, or underlying condition that would be expected to result in a bleeding diathesisXx_NEWLINE_xXGastrointestinal bleeding within the past one yearXx_NEWLINE_xXEvidence of active mucosal or internal bleeding.Xx_NEWLINE_xXHistory or evidence of bleeding disorder or active clinically significant bleeding requiring medical intervention.Xx_NEWLINE_xXSevere bleeding, hemoptysis, gastrointestinal hemorrhage, CNS bleeding, clinically significant hemorrhage or vaginal bleeding during the last 6 monthsXx_NEWLINE_xXIf they have had any active bleeding in the last =< 4 weeks or have an otherwise known bleeding diathesisXx_NEWLINE_xXActive uncontrolled bleeding or a known bleeding diathesisXx_NEWLINE_xXEvidence of active mucosal or internal bleeding.Xx_NEWLINE_xXActive hemoptysis (bright red blood of at least 0.5 teaspoon) or tumor bleeding within 3 weeks prior to the first dose of study drugXx_NEWLINE_xXHistory of clinically significant bleedingXx_NEWLINE_xXLesions with underlying infection or clinically meaningful bleedingXx_NEWLINE_xXKnown abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants precluding intramuscular injections of fulvestrant or goserelin (if applicable).Xx_NEWLINE_xXPatients who have a history or current evidence of bleeding disorder, i.e., any hemorrhage/bleeding event of CTCAE grade >= 2, =< 28 days prior to registrationXx_NEWLINE_xXPatients with active or prior digestive tract bleeding.Xx_NEWLINE_xXAny active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)Xx_NEWLINE_xXKnown bleeding disorders (e.g., von Willebrand’s disease) or hemophiliaXx_NEWLINE_xXPatients with an active, bleeding diathesisXx_NEWLINE_xXHas 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 excludedXx_NEWLINE_xXEvidence of active bleeding or bleeding diathesisXx_NEWLINE_xXAny hemorrhage or bleeding event >= CTCAE grade 3 within 4 weeks prior to the start of study medicationXx_NEWLINE_xXAny hemorrhage or bleeding event >= NCI CTCAE grade 3 within 4 weeks prior to start of study medicationXx_NEWLINE_xXHistory of significant congenital or acquired bleeding disorder unrelated to cancerXx_NEWLINE_xXFor 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 agentsXx_NEWLINE_xXKnown portal hypertension or history of variceal bleedingXx_NEWLINE_xXUnderlying condition predisposing them to bleeding or currently exhibits signs of clinically significant bleedingXx_NEWLINE_xXRecent history of non-chemotherapy-induced thrombocytopenic-associated bleeding =< 1 year prior to the registrationXx_NEWLINE_xXSubjects with history of known bleeding disorder(s) or history of clinically significant hemorrhage (e.g., gastrointestinal , neurologic), within the past 6 months.Xx_NEWLINE_xXSubjects with known bleeding diathesis will be excluded from the study.Xx_NEWLINE_xXPatients with history of bleeding diathesis are ineligibleXx_NEWLINE_xXDisseminated intravascular coagulopathy with active bleeding or signs of thrombosisXx_NEWLINE_xXParticipants with history of known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhage within 12 months of start of study drugXx_NEWLINE_xXKnown, increased risk of bleedingXx_NEWLINE_xXClinically-significant gastrointestinal disorders, such as perforation, gastrointestinal bleeding, or diverticulitis.Xx_NEWLINE_xXSubjects with history of bleeding diathesisXx_NEWLINE_xXPatients with evidence of active bleeding or bleeding diathesis will be excluded (patients with excess of 2.5 mL of hemoptysis are not eligible)Xx_NEWLINE_xXPatients with an underlying condition predisposing them to bleeding or currently exhibiting signs of clinically significant bleedingXx_NEWLINE_xXPatients with a recent history of non-chemotherapy-induced thrombocytopenic-associated bleeding within 1 year prior to the first dose of study drugXx_NEWLINE_xXActive bleeding disorder or other history of significant bleeding episodes within 30 days before study entryXx_NEWLINE_xXPatients with personal or family history of bleeding disorders are not eligibleXx_NEWLINE_xXGrade 2 or higher ongoing gastrointestinal hemorrhage; patients with grade 1 gastrointestinal bleeding are eligible for participationXx_NEWLINE_xXPatients with evidence of active bleeding diathesisXx_NEWLINE_xXPatients with evidence of active bleeding, intratumoral hemorrhage or history of bleeding diatheses, unless specifically occurring as an isolated incident during reversible chemotherapy-induced thrombocytopeniaXx_NEWLINE_xXPatients with evidence or history of bleeding diathesis; any hemorrhage or bleeding event >= CTCAE grade 3 within 4 weeks prior to registrationXx_NEWLINE_xXPatients 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 vesselsXx_NEWLINE_xXActive bleeding or a pathological condition that is associated with a high risk of bleeding (therapeutic anticoagulation is allowed)Xx_NEWLINE_xXPatients with bleeding disorders are ineligible due to lymph node removal possibly causing excessive bleeding; bleeding disorder will be defined by an INR level of > 2.0Xx_NEWLINE_xXThe 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 hemorrhageXx_NEWLINE_xXKnown bleeding disorders (e.g., von Willebrand’s disease) or hemophiliaXx_NEWLINE_xXAny hemorrhage or bleeding event >= grade 3 within 4 weeks prior to prior to registrationXx_NEWLINE_xXPatients with coagulation problems and active major bleeding within 4 weeks prior to cycle 1, day 1 (C1D1) (peptic ulcer, epistaxis, spontaneous bleeding)Xx_NEWLINE_xXPatients with an active, bleeding diathesisXx_NEWLINE_xXNo evidence of active bleedingXx_NEWLINE_xXHistory of significant bleeding disorder unrelated to cancer, including diagnosed congenital bleeding disorders (e.g., von Willebrand’s disease)Xx_NEWLINE_xXNo clinically significant gastrointestinal bleeding within 24 weeks before the first dose of study treatmentXx_NEWLINE_xXPatients with an active, bleeding diathesisXx_NEWLINE_xXAny active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)Xx_NEWLINE_xXNo history of abnormal bleeding tendencyXx_NEWLINE_xXPatients with an active, bleeding diathesisXx_NEWLINE_xXPulmonary hemorrhage/bleeding event >= CTCAE grade 2 within 4 weeks of first-dose of study drugXx_NEWLINE_xXAny other hemorrhage/bleeding event >= CTCAE grade 3 within 4 weeks of first dose of study drugXx_NEWLINE_xXPatients with an active, bleeding diathesisXx_NEWLINE_xXNo history of abnormal bleeding tendency or predisposition to repeated infectionsXx_NEWLINE_xXPatients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vesselsXx_NEWLINE_xXKnown hemorrhagic diathesis or active bleeding disorderXx_NEWLINE_xXPatients with any pulmonary hemorrhage/bleeding event grade 2 or higher within 4 weeks before randomizationXx_NEWLINE_xXFor 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 agentsXx_NEWLINE_xXThis 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 vesselsXx_NEWLINE_xXLung tumor lesions with increased likelihood of bleeding;Xx_NEWLINE_xXHistory of active bleeding within the last 3 months requiring transfusionXx_NEWLINE_xXThe participant has a significant bleeding disorder or vasculitis.Xx_NEWLINE_xXHas had esophageal or gastric variceal bleeding within the last 6 months.Xx_NEWLINE_xXHistory of CNS bleeding within 6 months of registrationXx_NEWLINE_xXAny sign of clinically significant bleedingXx_NEWLINE_xXPatients with active bleeding of the GI tract or patients who have symptoms associated with stomach irritation (known as gastritis).Xx_NEWLINE_xXBleeding 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.Xx_NEWLINE_xXActive bleeding diathesis or history of any major bleeding, central nervous system (CNS) bleeding, or significant hemoptysis within 6 months of enrollmentXx_NEWLINE_xXPatients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vesselsXx_NEWLINE_xXPatients who have experienced any grade 3-4 gastrointestinal (GI) bleeding within 3 months prior to first dose of protocol therapyXx_NEWLINE_xXSubjects with untreated or incompletely treated varices with bleeding or high risk for bleeding.Xx_NEWLINE_xXHistory of bleeding diathesis.Xx_NEWLINE_xXKnown history of a bleeding diathesis.Xx_NEWLINE_xXHave a history of uncontrolled hereditary or acquired bleeding or thrombotic disorders.Xx_NEWLINE_xXHave experienced a Grade ?3 bleeding event within 3 months (?3 months) prior to randomization.Xx_NEWLINE_xXknown bleeding disorders or hemophiliaXx_NEWLINE_xXEvidence of active bleeding or bleeding diathesisXx_NEWLINE_xXEvidence of active bleeding or bleeding diathesisXx_NEWLINE_xXClinically significant gastrointestinal bleeding within 6 months prior to the first dose of ALRN-6924Xx_NEWLINE_xXPreviously 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 monthsXx_NEWLINE_xXHistory of active clinically significant bleedingXx_NEWLINE_xXActive 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.Xx_NEWLINE_xXBleeding disorder (INR > ULN and PTT > ULN)Xx_NEWLINE_xXAny history of clinically meaningful variceal bleeding within the last three months.Xx_NEWLINE_xXClinically significant hemoptysis or tumor bleeding within two weeks prior to first dose of lenvatinib.Xx_NEWLINE_xXA 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.Xx_NEWLINE_xXHas active bleeding disorder or other history of significant bleeding episodes within 30 days of randomization.Xx_NEWLINE_xXUse of anti-coagulant agents or history a significant bleeding diathesis. (If a superficial lymph node or subcutaneous mass is to be injected, patients on agents such as non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, or clopidogrel are eligible and these agents do not have to be withheld. For procedures with moderate or significant risk of bleeding, long-acting agents such as aspirin or clopidogrel should be discussed with the Medical Monitor and may need to be discontinued before G100 therapy. For patients enrolled in Part 2 with the potential to receive pembrolizumab:Xx_NEWLINE_xXKnown inherited predisposition to bleeding or thrombosisXx_NEWLINE_xXPatients must not have active bleeding or a pathological condition that is associated with a high risk of bleedingXx_NEWLINE_xXHistory of major gastrointestinal bleeding within the last 6 months. Any evidence of active gastrointestinal bleeding excludes the subject.Xx_NEWLINE_xXNo 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 excludedXx_NEWLINE_xXHistory of congenital bleeding diathesisXx_NEWLINE_xXSignificant hematologic, gastrointestinal, thromboembolic, vascular, bleeding, or coagulation disorders.Xx_NEWLINE_xXPatients with active bleeding or pathologic conditions that carry high risk of bleedingXx_NEWLINE_xXPatients 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 excludedXx_NEWLINE_xXKnown bleeding disorders (e.g., von Willebrand’s disease) or hemophiliaXx_NEWLINE_xXAny hemorrhage or bleeding event >= NCI CTCAE grade 3 within 4 weeks prior to start of study medicationXx_NEWLINE_xXAnemia due to factors other than MDS, CMML, or AML (including hemolysis or gastrointestinal bleeding).Xx_NEWLINE_xXPatient has evidence of mucosal or internal bleeding and/or is platelet transfusion refractoryXx_NEWLINE_xXActive bleeding or pathologic condition that carries a high risk of bleeding (e.g. hereditary hemorrhagic telangiectasia).Xx_NEWLINE_xXPulmonary hemorrhage/bleeding event >= CTCAE grade 2 within 4 weeks of study registrationXx_NEWLINE_xXAny other hemorrhage/bleeding event >= CTCAE grade 3 within 4 weeks of study registrationXx_NEWLINE_xXMajor upper gastrointestinal bleeding episode occurring during the previous year before screening.Xx_NEWLINE_xXEvidence 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 C1D1Xx_NEWLINE_xXA 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)Xx_NEWLINE_xXhave 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 interventionXx_NEWLINE_xXHas had esophageal or gastric variceal bleeding within the last 6 monthsXx_NEWLINE_xXKnown bleeding disorders (eg, von Willebrand’s disease) or hemophiliaXx_NEWLINE_xXAny hemorrhage or bleeding event ? NCI CTCAE Grade 3 within 4 weeks prior to start of study medication.Xx_NEWLINE_xXKnown bleeding disorders (e.g., severe von Willebrand’s disease) or severe hemophiliaXx_NEWLINE_xXActive uncontrolled bleedingXx_NEWLINE_xXHave significant bleeding disorders, vasculitis, or had a significant bleeding episode from the gastrointestinal tract within 12 weeks prior to randomization.Xx_NEWLINE_xXPatients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder or coagulopathy.Xx_NEWLINE_xXKnown inherited predisposition to bleeding or thrombosisXx_NEWLINE_xXFor 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.Xx_NEWLINE_xXPulmonary hemorrhage/bleeding event > or equal to CTCAE v4 grade 2 within 4 weeks of first dose of study drugXx_NEWLINE_xXAny other hemorrhage/bleeding event > or equal to CTCAE v4 grade 3 within 4 weeks of first dose of study drugXx_NEWLINE_xXPatients at risk of non-AML related major bleeding (e.g. recent gastrointestinal [GI] hemorrhage or neurosurgery).Xx_NEWLINE_xXActive bleeding diathesisXx_NEWLINE_xXHistory of gastrointestinal ulcer or bleeding within 3 months; any digestive tract dysfunctionXx_NEWLINE_xXSevere gastrointestinal bleeding within 12 weeks of treatment with G-202Xx_NEWLINE_xXOngoing major bleeding,Xx_NEWLINE_xXHistory 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)Xx_NEWLINE_xXGastrointestinal bleeding event or active hemoptysis (bright red blood of at least 0.5 teaspoon) within 28 days prior to randomizationXx_NEWLINE_xXThe 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 hemorrhageXx_NEWLINE_xXSignificant gastrointestinal bleeding within 6 weeks prior to consent.Xx_NEWLINE_xXPortosystemic hypertension or known history of bleeding esophageal varices.Xx_NEWLINE_xXPatients with an uncontrolled bleeding disorderXx_NEWLINE_xXHistory of significant congenital or acquired bleeding disorderXx_NEWLINE_xXParticipant has a history of uncontrolled hereditary or acquired bleeding or thrombotic disordersXx_NEWLINE_xXParticipant has active, high risk bleeding (such as, via gastric ulcers or gastric varices) within 14 days prior to randomizationXx_NEWLINE_xXPatients with history of bleeding diathesisXx_NEWLINE_xXHistory of hemolytic anemia or bleeding diathesisXx_NEWLINE_xXHistory of clinically-significant cardiovascular disease; gastrointestinal perforation; gastrointestinal bleeding, acute pancreatitis or diverticulitis within 4 weeks of first study drug administrationXx_NEWLINE_xXIn the opinion of the investigator, bleeding diathesis or anticoagulation therapy that would preclude intramuscular injectionsXx_NEWLINE_xXHistory 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 excludedXx_NEWLINE_xXKnown inherited predisposition to bleeding or thrombosisXx_NEWLINE_xXHave 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.Xx_NEWLINE_xXAny hemorrhage or bleeding event >= NCI CTCAE grade 3 within 4 weeks prior to start of study medicationXx_NEWLINE_xXPatients with known bleeding diathesis (e.g. von Willebrand ‘s disease) or hemophiliaXx_NEWLINE_xXHistory of significant congenital or acquired bleeding disorder unrelated to cancerXx_NEWLINE_xXHistory of major gastrointestinal bleeding within the last 6 months.Xx_NEWLINE_xXKnown bleeding disorders with the exception of acquired Von Willebrand disorder suspected on the basis of WMXx_NEWLINE_xXKnown bleeding disorders (e.g., von Willebrand disease or hemophilia)Xx_NEWLINE_xXKnown bleeding diathesis (e.g., von Willebrand’s disease) or hemophiliaXx_NEWLINE_xXSubject has a history of bleeding esophageal varices within 3 months before the Day 1 visit.Xx_NEWLINE_xXContraindications 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)Xx_NEWLINE_xXActive bleeding diathesisXx_NEWLINE_xXPatients with history of gastrointestinal (GI) bleeding and peptic ulcer disease within the past 6 monthsXx_NEWLINE_xXActive 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 excludedXx_NEWLINE_xXAny hemorrhage or bleeding event >= NCI CTCAE grade 3 within 4 weeks prior to start of study medicationXx_NEWLINE_xXSubject has a contraindication to receiving IM injections (eg, bleeding disorders, anticoagulant use).Xx_NEWLINE_xXEvidence or history of bleeding diathesis or any hemorrhage or bleeding event > CTCAE grade 3 =< 4 weeks prior to randomizationXx_NEWLINE_xXSubjects with uncontrolled bleeding disorder which cannot be controlled with anticoagulantsXx_NEWLINE_xXHas history of known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhage within 12 months of start of study drugXx_NEWLINE_xXSubjects with a history of intestinal perforation, colitis, clinically significant gastrointestinal bleeding or intestinal obstruction within one year prior to enrollment.Xx_NEWLINE_xXPatients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vesselsXx_NEWLINE_xXSignificant history of bleeding events or pre-existing bleeding diathesis =< 6 months of randomization (unless the source of bleeding has been resected)Xx_NEWLINE_xXPatients with a history of significant tumor bleeding, or coagulation or bleeding disorders.Xx_NEWLINE_xXThe 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 excludedXx_NEWLINE_xXHistory of significant bleeding disorder unrelated to cancerXx_NEWLINE_xXPatients with active bleeding diathesisXx_NEWLINE_xXConcurrent 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 infectionXx_NEWLINE_xXEvidence of blood clotting or bleeding abnormalitiesXx_NEWLINE_xXKnown bleeding disorders or hemophilia.Xx_NEWLINE_xXPatients with coagulation problems and active bleeding in the last month (peptic ulcer, epistaxis, spontaneous bleeding)Xx_NEWLINE_xXKnown bleeding disorders (eg, von Willebrand's disease) or hemophilia.Xx_NEWLINE_xXPatients with evidence or history of any bleeding diathesis, irrespective of severityXx_NEWLINE_xXSubjects with a bleeding diathesis (e.g., von Willebrand’s disease or hemophilia) are not eligibleXx_NEWLINE_xXSubjects 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 treatmentXx_NEWLINE_xXPatients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vesselsXx_NEWLINE_xXAny hemorrhage or bleeding event >= NCI CTCAE grade 3 within 4 weeks prior to start of study medicationXx_NEWLINE_xXAny hemorrhage or bleeding event >= NCI CTCAE grade 3 within 4 weeks prior to start of study medicationXx_NEWLINE_xXEvidence 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;Xx_NEWLINE_xXHave a history of or active significant gastrointestinal (GI) bleeding within 3 months of the first dose of brigatinib.Xx_NEWLINE_xXPatients must not have any evidence of bleeding diathesis or active gastrointestinal bleedingXx_NEWLINE_xXNo patients with clinically significant gastrointestinal (GI) bleeding or bleeding diathesis within 30 days prior to registrationXx_NEWLINE_xXHistory of bleeding (i.e. disseminated intravascular coagulation or clotting factor deficiency);Xx_NEWLINE_xXPulmonary hemorrhage/bleeding event >= CTCAE grade 2 within 4 weeks of first dose of study drugXx_NEWLINE_xXAny other hemorrhage/bleeding event >= CTCAE grade 3 within 4 weeks of first dose of study drugXx_NEWLINE_xXPatient must not have any known bleeding disorders (e.g., von Willebrand’s disease) or hemophiliaXx_NEWLINE_xXHas had significant bleeding/thrombosis in previous 4 weeksXx_NEWLINE_xXPatients 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 treatmentXx_NEWLINE_xXPatients with known bleeding disorders or more than punctate intratumoral hemorrhage are excludedXx_NEWLINE_xXPatients requiring anticoagulation or with uncontrolled bleeding are excludedXx_NEWLINE_xXHistory of upper gastrointestinal bleeding, ulceration, or perforation within 12 months prior to the first dose of study drugXx_NEWLINE_xXHistory of clinically significant gastrointestinal (GI) bleeding within prior 2 months prior to enrollmentXx_NEWLINE_xXEvidence of mucosal or internal bleedingXx_NEWLINE_xXEvidence of active bleeding or bleeding diathesisXx_NEWLINE_xXConcurrent 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)-positiveXx_NEWLINE_xXClinically significant hemoptysis or tumor bleeding within 2 weeks prior to first dose of lenvatinibXx_NEWLINE_xXPatients with untreated or incompletely treated varices with bleeding or high-risk for bleedingXx_NEWLINE_xXBleeding diathesis or use of warfarin or other vitamin K antagonistXx_NEWLINE_xXGastrointestinal bleeding or active hemoptysis (bright red blood of at least half teaspoon) within 21 days prior to enrollmentXx_NEWLINE_xXKnown bleeding disorders (e.g. von Willebrand’s disease) or hemophiliaXx_NEWLINE_xXPART B: History of clinically significant bleeding disorderXx_NEWLINE_xXAny active uncontrolled bleeding or bleeding diathesisXx_NEWLINE_xXEvidence of active bleeding or bleeding diathesisXx_NEWLINE_xXSubject with any pulmonary hemorrhage/bleeding event of NCI-CTCAE v4.0 grade 2 or higher within 4 weeks before treatment; any other hemorrhage/bleeding event of NCI-CTCAE v4.0 grade 3 or higher within 4 weeks before treatmentXx_NEWLINE_xXPresence 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 thrombocytopenicXx_NEWLINE_xXKnown bleeding disorders (e.g., von Willebrand’s disease) or hemophiliaXx_NEWLINE_xXSignificant 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)Xx_NEWLINE_xXSubject with any pulmonary hemorrhage/bleeding event of NCI-CTCAE v4.0 grade 2 or higher within 4 weeks before randomization; any other hemorrhage/bleeding event of NCI-CTCAE v4.0 grade 3 or higher within 4 weeks before study entryXx_NEWLINE_xXNo 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 perforationXx_NEWLINE_xXNo evidence of active bleeding, bleeding diathesis, or hemoptysis (>= 1/2 teaspoon of red blood) within 8 weeks prior to registrationXx_NEWLINE_xXBleeding esophageal or gastric varices within 30 days prior to treatment initiationXx_NEWLINE_xXHistory of bleeding diathesisXx_NEWLINE_xXAny active uncontrolled bleeding and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)Xx_NEWLINE_xXPrevious major bleed (bleeding requiring transfusion of red blood cells) on LMWHXx_NEWLINE_xXPatients must not have any evidence of bleeding diathesis or active gastrointestinal bleedingXx_NEWLINE_xXAny active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)Xx_NEWLINE_xXEvidence of active bleeding or bleeding diathesisXx_NEWLINE_xXHistory 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 therapyXx_NEWLINE_xXHistory of bleeding diathesis or extensive bleeding requiring blood transfusion within 14 days of enrollmentXx_NEWLINE_xXHistory of significant congenital or acquired bleeding disorder unrelated to cancerXx_NEWLINE_xXHistory of clinically significant bleeding episodesXx_NEWLINE_xXSubject with any pulmonary hemorrhage/bleeding event of NCI-CTCAE v4.0 grade 2 or higher within 4 weeks before enrollment; any other hemorrhage/bleeding event of NCI-CTCAE v4.0 grade 3 or higher within 4 weeks before enrollmentXx_NEWLINE_xXClinically significant bleeding NCI-CTCAE version 4.0 Grade 3 or higher within 30 days before randomization.Xx_NEWLINE_xXVaginal bleeding of unknown etiology within 12 months of study entryXx_NEWLINE_xXPatient must not have evidence of active bleeding or bleeding diathesisXx_NEWLINE_xXDocumented or known clinically significant bleeding disorder.Xx_NEWLINE_xXKnown presence of a significant congenital or acquired bleeding disorder unrelated to cancerXx_NEWLINE_xXHistory of clinically significant bleeding within 6 months of enrollment/randomizationXx_NEWLINE_xXHistory 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 excludedXx_NEWLINE_xXPatients who have a history of bleeding disorders including congenital or acquired coagulopathiesXx_NEWLINE_xXHistory 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 bleedingXx_NEWLINE_xXActive uncontrolled bleedingXx_NEWLINE_xXBleeding\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 allowedXx_NEWLINE_xXContraindications to seed placement, including uncontrollable bleeding diathesisXx_NEWLINE_xXEvidence of active bleeding or bleeding diathesisXx_NEWLINE_xXThe 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 hemorrhageXx_NEWLINE_xXPatients with an active, bleeding diathesisXx_NEWLINE_xXEvidence of active bleeding or bleeding diathesisXx_NEWLINE_xXHistory of gastrointestinal (GI) bleeding (hemoptysis/melena/hematochezia, >= 1/2 teaspoon of bright red blood per episode) within 1 month prior to day 1Xx_NEWLINE_xXSignificant history of bleeding events or pre-existing bleeding diathesis, within 6 months of randomization (unless the source of bleeding has been resected)Xx_NEWLINE_xXUncontrolled severe bleeding tendency or active GI bleedingXx_NEWLINE_xXActive bleeding or bleeding susceptibilityXx_NEWLINE_xXEvidence of active bleeding or bleeding diathesisXx_NEWLINE_xXEvidence of active bleeding or bleeding diathesisXx_NEWLINE_xXActive bleeding or a pathological condition that is associated with a high risk of bleedingXx_NEWLINE_xXHistory of bleeding (hemoptysis in excess of 2.5 mL or one-half teaspoon, hematuria, gastrointestinal [GI] blood loss, epistaxis, or others with greater than grade 1 according to Common Terminology Criteria for Adverse Events [CTCAE] version 4.0) within 1 month prior to beginning therapy or any clinical indications of current active bleedingXx_NEWLINE_xXHistory of significant congenital or acquired bleeding disorder unrelated to cancerXx_NEWLINE_xXEvidence of active bleeding or bleeding diathesisXx_NEWLINE_xXSerious bleeding diathesis or those who are on therapeutic anticoagulationXx_NEWLINE_xXEvidence or history of bleeding diathesis; any hemorrhage or bleeding event >= grade 4 within 4 weeks of start of FOLFIRIXx_NEWLINE_xXClinically 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 hemorrhageXx_NEWLINE_xXHave a significant bleeding disorder unrelated to CML or Ph+ALLXx_NEWLINE_xXEvidence of active bleeding or bleeding diathesisXx_NEWLINE_xXEXPANSION COHORT ONLY: Evidence of active bleeding or bleeding diathesisXx_NEWLINE_xXEXPANSION 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 perforationXx_NEWLINE_xXKnown history of bleeding disorders (e.g., von Willebrand disease or hemophilia).Xx_NEWLINE_xXClinically significant bleeding such as gross hematuria, gastrointestinal bleeding and hemoptysis within 6 months prior to enrollment.Xx_NEWLINE_xXKnown bleeding diathesis (e.g., von Willebrand's disease) or hemophiliaXx_NEWLINE_xXClinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drugXx_NEWLINE_xXPatients 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.Xx_NEWLINE_xXContraindication 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 fractureXx_NEWLINE_xXPatients with active bleeding, including hemoptysis within 4 weeks of enrollment should be excluded, as there is no safety data with vorinostat in this settingXx_NEWLINE_xXKnown bleeding diathesisXx_NEWLINE_xXHistory of severe gastrointestinal bleeding within 6 months; patients with gastrointestinal blood loss due to KS may be includedXx_NEWLINE_xXBleeding disorderXx_NEWLINE_xXHistory of underlying bleeding disorder, such as hemophiliaXx_NEWLINE_xXHistory of gastro-intestinal bleeding within 12 monthsXx_NEWLINE_xXRecent history (within 1 year of first dose) of underlying, predisposing condition of bleeding or currently exhibits signs of bleedingXx_NEWLINE_xXHistory 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)Xx_NEWLINE_xXSubject has history of gastrointestinal ulcer or gastrointestinal bleeding within 3 months prior to the planned first dose of study drug.Xx_NEWLINE_xXKnown systemic bleeding or platelet disorderXx_NEWLINE_xXPatients with poorly controlled bleeding from gastric antral vascular ectasia (GAVE) or other gastrointestinal (GI) sitesXx_NEWLINE_xXOngoing 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.Xx_NEWLINE_xXAny hemorrhage or bleeding event ? NCI CTCAE Grade 3 within 4 weeks prior to study registration.Xx_NEWLINE_xXSuffering from a known bleeding disorder.Xx_NEWLINE_xXSignificant 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;Xx_NEWLINE_xXFor 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.Xx_NEWLINE_xXSubjects with current/a history of bleeding disorder or coagulopathy or who are at particularly high risk for bleeding complications.Xx_NEWLINE_xXHistory of upper gastrointestinal bleeding, ulceration, or perforation within 12 months prior to the first dose of study drug.Xx_NEWLINE_xXSubject has active gastrointestinal ulcer or gastrointestinal bleeding within 3 months prior to the planned first dose of study drug.Xx_NEWLINE_xXHistory of upper gastrointestinal bleeding, ulceration, or perforation within 6 months prior to the first dose of protocol therapyXx_NEWLINE_xXKnown congenital bleeding disorders such as hemophiliaXx_NEWLINE_xXNo history of major bleeding, recent or active myocardial ischemia, gastrointestinal (GI) perforation, cerebrovascular accidents or other significant illnessXx_NEWLINE_xXSubject has severe or uncontrolled systemic diseases or active bleeding diatheses.Xx_NEWLINE_xXSubject has a history of gastrointestinal bleeding within 90 days prior to the first dose of study drug.Xx_NEWLINE_xXSubjects 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.Xx_NEWLINE_xXKnown inherited predisposition to bleeding or thrombosisXx_NEWLINE_xXOngoing risk of bleeding.Xx_NEWLINE_xXEvidence 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 drugXx_NEWLINE_xXActive bleeding disorders or clinical signs of bleeding (Grade ?2).Xx_NEWLINE_xXKnown bleeding disorders (e.g., von Willebrand's disease) or hemophilia.Xx_NEWLINE_xXInternational normalized ratio > 1.5 on anticoagulant therapy, active bleeding on low molecular weight heparin, or chronic condition with a high risk of bleeding.Xx_NEWLINE_xXAny hemorrhage or bleeding event >= NCI CTCAE grade 3 within 4 weeks prior to start of study medicationXx_NEWLINE_xXHistory of significant congenital or acquired bleeding disorder unrelated to cancerXx_NEWLINE_xXActive bleeding within 4 weeks prior to screening visitXx_NEWLINE_xXAny hemorrhage or bleeding event >= NCI CTCAE v.4.0 grade 3 within 4 weeks prior to start of study medicationXx_NEWLINE_xXNo 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 excludedXx_NEWLINE_xXAny active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)Xx_NEWLINE_xXAny hemorrhage or bleeding eventXx_NEWLINE_xXActive 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.Xx_NEWLINE_xXPatients taking anticoagulants or with a history of a bleeding diathesisXx_NEWLINE_xXClinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleedingXx_NEWLINE_xXEvidence of active bleeding or bleeding diathesisXx_NEWLINE_xXActive bleeding that requires hospitalization during the screening periodXx_NEWLINE_xXHistory of medically significant thromboembolic events or bleeding diathesis within the past 6 monthsXx_NEWLINE_xXEvidence of active bleeding or bleeding diathesis; any medical condition requiring systemic anticoagulation (including anti-platelet agents)Xx_NEWLINE_xXHave evidence or history of any bleeding diathesis (including mild hemophilia), irrespective of severity.Xx_NEWLINE_xXHave had a hemorrhage or a bleeding event >/=Grade 3 (NCI-CTCAE v 4.0) within 4 weeks prior to the initiation of study treatment.Xx_NEWLINE_xX3. History of upper GI bleeding, ulceration, or perforation within 12 months prior to the first dose of study drug.Xx_NEWLINE_xXHistory of upper gastrointestinal bleeding, ulceration, or perforation within 12 months.Xx_NEWLINE_xXEvidence of a bleeding diathesis that cannot be corrected with standard therapy or factor replacementXx_NEWLINE_xXClinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding.Xx_NEWLINE_xXEvidence of active bleeding or bleeding diathesis.Xx_NEWLINE_xXHistory of active peptic ulcer disease or major upper gastrointestinal (GI) bleed < 12 months; history of GI bleeding from the colorectal cancer primary is not an exclusion criterionXx_NEWLINE_xXHistory of perforation or bleeding related to peptic ulcer diseaseXx_NEWLINE_xXHistory of unexplained bleeding episodes within 3 months of M402 dosingXx_NEWLINE_xXPulmonary hemorrhage/bleeding event >= CTCAE grade 2 within 4 weeks of first dose of study drugXx_NEWLINE_xXAny other hemorrhage/bleeding event >= CTCAE grade 3 within 4 weeks of first dose of study drugXx_NEWLINE_xXCurrent (significant or uncontrolled) gastrointestinal bleedingXx_NEWLINE_xXParticipants with a recent history (< 6 months) of a major bleed which will be defined as a symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome, and/or bleeding causing a fall in hemoglobin level 2 grams/dL or more, or leading to transfusion of two or more units of whole blood or packed red cellsXx_NEWLINE_xXPrior 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.Xx_NEWLINE_xXPatients with an active, bleeding diathesisXx_NEWLINE_xXPulmonary hemorrhage/bleeding event > CTCAE grade 2 within 4 weeks of study entryXx_NEWLINE_xXAny other hemorrhage/bleeding event > CTCAE grade 3 within 4 weeks of study entryXx_NEWLINE_xXEvidence or history of any bleeding or coagulation disorderXx_NEWLINE_xXAny sign of clinically significant bleedingXx_NEWLINE_xXRecent hemoptysis >2.5 mL or serious bleeding from another site, known bleeding disorder or coagulopathy or therapeutic anti-coagulationXx_NEWLINE_xXHave significant bleeding disorders, vasculitis, or had a significant bleeding episode from the gastrointestinal (GI) tract within 3 months prior to receiving study drugs.Xx_NEWLINE_xXActive bleeding or high risk for bleeding contraindicating treatment with LMWH or edoxaban;Xx_NEWLINE_xXHistory of gastrointestinal bleeding within the past 6 monthsXx_NEWLINE_xXHistory of bleeding diathesis or known qualitative platelet defect (including von Willebrand disease)Xx_NEWLINE_xXEsophageal variceal bleeding within 2 weeks prior to the first dose of TKM-080301.Xx_NEWLINE_xXKnown bleeding diathesis or hemophiliaXx_NEWLINE_xXClinically significant bleeding within 30 days before enrollmentXx_NEWLINE_xXHistory 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 excludedXx_NEWLINE_xXHistory of bleeding diasthesisXx_NEWLINE_xXParticipants 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 entryXx_NEWLINE_xXBleeding esophageal or gastric varices within 2 months before enrollment.Xx_NEWLINE_xXOngoing major bleeding,Xx_NEWLINE_xXPatients with coagulation problems and active bleeding in the last month (peptic ulcer, epistaxis, spontaneous bleeding)Xx_NEWLINE_xXActive bleeding; pathological condition that carries a high risk of bleeding; risk of pseudoaneurysm of the internal carotid artery and carotid blowout syndrome.Xx_NEWLINE_xXKnown bleeding disorders (e.g., von Willebrand’s disease) or hemophiliaXx_NEWLINE_xXActive bleeding disorders or evidence of evidence of chronic or acute disseminated intravascular coagulation (DIC)Xx_NEWLINE_xXPatients with known bleeding diathesis or prothrombin time (PT) or aPTT >1.5 x ULN or fibrinogen <0.5 x LLNXx_NEWLINE_xXUncontrolled peptic or gastric ulcer disease, or gastrointestinal bleeding within prior 6 monthsXx_NEWLINE_xXPatients with acute gastrointestinal bleeding within 1 month of study entryXx_NEWLINE_xXHas history of known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhage within 12 months of start of study drug.Xx_NEWLINE_xXEsophageal or gastric variceal bleeding within last 3 monthsXx_NEWLINE_xXAny other hemorrhage or bleeding of Grade ?3 within 28 days prior to first dose of study treatmentXx_NEWLINE_xXKnown active gastrointestinal (GI) bleeding.Xx_NEWLINE_xXKnown bleeding diathesis Known history of hereditary hemorrhagic telangiectasia (HHT).Xx_NEWLINE_xXEndometrial bleedingXx_NEWLINE_xXKnown history of bleeding disorders, eg, von Willebrand disease or hemophiliaXx_NEWLINE_xXClinically significant bleeding such as gross hematuria, GI bleeding, and hemoptysis within the 6 months before screeningXx_NEWLINE_xXDoes the subject have any bleeding diathesis, or must the subject take any anticoagulants, or antiplatelet agents, including NSAIDs that cannot be stopped for surgery?Xx_NEWLINE_xXPatients 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 antibodiesXx_NEWLINE_xXActive bleedingXx_NEWLINE_xXKnown inherited predisposition to bleeding or thrombosisXx_NEWLINE_xXEvidence or history of bleeding disorder, i.e. any hemorrhage / bleeding event of > Grade 2 within 4 weeks prior to the first dose of study drugXx_NEWLINE_xXThe 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 hemorrhageXx_NEWLINE_xXSubjects 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 treatmentXx_NEWLINE_xXPatients with an underlying diagnosis or disease state associated with an increased risk of bleeding.Xx_NEWLINE_xXPART I: History of bleeding disorderXx_NEWLINE_xXPART II: History of bleeding disorderXx_NEWLINE_xXPatient 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 drugXx_NEWLINE_xXActive, bleeding diathesis.Xx_NEWLINE_xXHistory of bleeding diathesis, known factor X deficiency (level < 20%), or requirement for therapeutic anticoagulation with warfarinXx_NEWLINE_xXPatients with a history of/or active bleeding disordersXx_NEWLINE_xXClinically significant gastrointestinal bleeding occurring <= 4 weeks prior to randomizationXx_NEWLINE_xXTarget bleeding site has moderate bleeding according to the Investigator's judgment.Xx_NEWLINE_xXThe target bleeding site has a mild or severe bleeding.Xx_NEWLINE_xXUncorrected bleeding disorder.Xx_NEWLINE_xXIf receiving warfarin: INR ? 3.0 (and no active bleeding, [i.e., no bleeding within 14 days prior to first dose of study therapy])Xx_NEWLINE_xXKnown bleeding diathesis.Xx_NEWLINE_xXNo known bleeding disordersXx_NEWLINE_xXNo active bleedingXx_NEWLINE_xXNo active bleedingXx_NEWLINE_xXActive bleeding or high risk of bleedingXx_NEWLINE_xXActive gastrointestinal bleedingXx_NEWLINE_xXHistory of significant bleeding disorder unrelated to cancer, including:Xx_NEWLINE_xXDiagnosed congenital bleeding disorders (e.g., von Willebrand's disease)Xx_NEWLINE_xXHistory of GI bleeding within 6 months of Screening visitXx_NEWLINE_xXEvidence 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 allowedXx_NEWLINE_xXFor patients undergoing serial tumor biopsies, known bleeding diathesis or history of abnormal bleeding or require anti-coagulation therapy.Xx_NEWLINE_xXNo history of bleeding diathesis.Xx_NEWLINE_xXAny hemorrhage or bleeding event >= grade 3 within 4 weeks prior to registrationXx_NEWLINE_xXThe subject has experienced any of the following\r\n* Clinically-significant gastrointestinal bleeding within 3 months before the first dose of study treatment; the participant must be maintained on a prophylactic regimen for management of an upper gastrointestinal (GI) bleeding event with no evidence of recurrence and/or endoscopic confirmation of resolution of the source of a lower GI bleed\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 treatmentXx_NEWLINE_xXAny other hemorrhage/bleeding event >= NCI-CTCAE grade 3 within 4 weeks of enrollmentXx_NEWLINE_xXActive bleedingXx_NEWLINE_xXPatients with an active, bleeding diathesisXx_NEWLINE_xXNo gastrointestinal bleeding within 1 year of study entry.Xx_NEWLINE_xXKnown bleeding diathesis, esophageal varices, or angioplastyXx_NEWLINE_xXHistory of clinically significant bleeding within 6 months of enrollment/randomizationXx_NEWLINE_xXHistory of bleeding diathesisXx_NEWLINE_xXHistory 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)Xx_NEWLINE_xXPatients with clinical bleeding, active gastric, or duodenal ulcerXx_NEWLINE_xXClinically significant gastrointestinal (GI) abnormalities that may increase the risk for GI bleeding.Xx_NEWLINE_xXEvidence of active bleeding or bleeding diathesis.Xx_NEWLINE_xXNo bleeding diathesisXx_NEWLINE_xXPatients with a history of familial bleeding disordersXx_NEWLINE_xXPatients must not have any evidence of bleeding diathesis or signs of active bleedingXx_NEWLINE_xXPulmonary hemorrhage/bleeding event >= CTCAE v 4.0 grade 2 within 4 weeks of first dose of study drugXx_NEWLINE_xXAny other hemorrhage/bleeding event >= CTCAE v 43.0 grade 3 within 4 weeks of first dose of study drugXx_NEWLINE_xXClinically 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.Xx_NEWLINE_xXHistory of bleeding diathesisXx_NEWLINE_xXKnown bleeding diathesisXx_NEWLINE_xXPatients with evidence of a bleeding diathesis that cannot be corrected with standard therapy or factor replacementXx_NEWLINE_xXHas a history of uncontrolled hereditary or acquired bleeding or thrombotic disordersXx_NEWLINE_xXHas experienced a Grade ? 3 bleeding event within 3 months prior to randomizationXx_NEWLINE_xXPatients with an active, bleeding diathesisXx_NEWLINE_xXAny other hemorrhage/bleeding event >= CTCAE grade 3 within 4 weeks of first dose of study drugXx_NEWLINE_xXExperienced any serious Grade 3-4 gastrointestinal bleeding within 3 months prior to study entryXx_NEWLINE_xXfor intratumoral cohort, bleeding diathesis or use of anticoagulants/antiplatelet agents that cannot be stoppedXx_NEWLINE_xXPatients 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 reconstructionXx_NEWLINE_xXEvidence of active bleeding or bleeding diathesisXx_NEWLINE_xXPatients with an active, bleeding diathesisXx_NEWLINE_xXAny other hemorrhage/bleeding event >= CTCAE Grade 3 within 4 weeks of first dose of study drugXx_NEWLINE_xXPatients with an active, bleeding diathesisXx_NEWLINE_xXHistory of major thrombotic or clinically relevant major bleeding event in the past 6 monthsXx_NEWLINE_xXBleeding diathesis, resulting in symptomatic bleeding.Xx_NEWLINE_xXHistory of bleeding disordersXx_NEWLINE_xXHistory 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)Xx_NEWLINE_xXSubject has history of gastrointestinal ulcer or gastrointestinal bleeding within 3 months prior to the first dose of study drug.Xx_NEWLINE_xXActive bleedingXx_NEWLINE_xXActive bleeding that requires hospitalization during the screening periodXx_NEWLINE_xXPatients with coagulation problems and active bleeding in the last month (peptic ulcer, epistaxis, spontaneous bleeding)Xx_NEWLINE_xXEvidence of active bleeding or pathologic conditions that carry high risk of bleeding such as known bleeding disorders, coagulopathy or tumor involving major vesselsXx_NEWLINE_xXEvidence of active bleeding or bleeding diathesisXx_NEWLINE_xXNo 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 perforationXx_NEWLINE_xXNo evidence of active bleeding, bleeding diathesis, or hemoptysis (>= ½ teaspoon of red blood) within 8 weeks of registrationXx_NEWLINE_xXNo known bleeding diathesisXx_NEWLINE_xXNo central lung metastases with excessive active bleedingXx_NEWLINE_xXInherited predisposition to bleeding or thrombosisXx_NEWLINE_xXHistory 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 surgeryXx_NEWLINE_xXKnown predisposition to bleedingXx_NEWLINE_xXSubject has ? grade 2 bleeding at the time of randomizationXx_NEWLINE_xXSubject with known congenital bleeding disorders or platelet dysfunctionXx_NEWLINE_xXActive grade >= 2 bleeding at the time of randomization, including hematuriaXx_NEWLINE_xXHistory of grade 4 bleedingXx_NEWLINE_xXPatients at risk of non-disease related major bleeding (eg, recent GI hemorrhage or neurosurgery, within previous 21 days).Xx_NEWLINE_xXClinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drugXx_NEWLINE_xXNo 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 registrationXx_NEWLINE_xXNo clinical signs active of bleedingXx_NEWLINE_xXPatients with overt bleedingXx_NEWLINE_xXKnown bleeding disordersXx_NEWLINE_xXKnown bleeding disorder per patient reported historyXx_NEWLINE_xXKnown bleeding or thrombotic diathesisXx_NEWLINE_xXActive bleeding or high risk of bleeding in the opinion of the investigatorXx_NEWLINE_xXBleeding diathesis or inability to hold anticoagulation for surgeryXx_NEWLINE_xXPersistent oral bleeding: > 15 mL (estimated) per dayXx_NEWLINE_xXActive bleeding (grade 2 or higher) at the time of enrollmentXx_NEWLINE_xXHistory of intracranial bleeding at any timeXx_NEWLINE_xXAny hemorrhage or bleeding event >= NCI CTCAE grade 3 within 4 weeks prior to start of study medicationXx_NEWLINE_xXActive bleedingXx_NEWLINE_xXAny 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 randomizationXx_NEWLINE_xXRecent or ongoing clinically significant gastrointestinal disorder (e.g., malabsorption, bleeding, inflammation, emesis, diarrhea > grade 1)Xx_NEWLINE_xXParticipants with untreated or incompletely treated varices with bleeding or high-risk for bleedingXx_NEWLINE_xXKnown bleeding disorders (eg, von Willebrand’s disease or hemophilia), active bleeding disorders or clinical signs of bleeding (grade >= 2)Xx_NEWLINE_xXKnown bleeding disorders (e.g., von Willebrand’s disease) or hemophiliaXx_NEWLINE_xXHas known bleeding diathesis that would be a safety risk;Xx_NEWLINE_xXAny bleeding episode considered life-threatening, or any Grade 3 or 4 gastrointestinal bleeding episode in the 3 months prior to randomization requiring intervention.Xx_NEWLINE_xXEsophageal 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.Xx_NEWLINE_xXUncontrolled hereditary or acquired thrombotic or bleeding disorder.Xx_NEWLINE_xXHistory of major bleeding (requiring a blood transfusion ? 2 units) not related to a tumor within the past 12 monthsXx_NEWLINE_xXPatient has a known bleeding diathesis (e.g. von Willebrand’s disease) or hemophiliaXx_NEWLINE_xXActive or serious bleeding within two weeks of enrollmentXx_NEWLINE_xXPatient condition associated with a high risk of bleeding such as recent surgery or peptic ulcer diseaseXx_NEWLINE_xXActive bleeding diathesisXx_NEWLINE_xXPatients must not have a severe bleeding disorderXx_NEWLINE_xXRecent acute bleeding requiring intervention in less than 24 hoursXx_NEWLINE_xXPatients will also be excluded if they have active bleeding, acute thrombosis, ischemia, hemodynamically unstable, and uncontrolled painXx_NEWLINE_xXCongenital bleeding disorder or predisposition to priapism that is contraindicative to vacuum constriction\r\ndevices (VCD) useXx_NEWLINE_xXNon-correctable bleeding diathesisXx_NEWLINE_xXThe subject has a history of significant bleeding disordersXx_NEWLINE_xXPatient used any medication that increases the risk of bleeding within 24 hours before the start of study treatment.Xx_NEWLINE_xXHistory of significant adverse reaction or major bleeding related adverse reaction to other anticoagulant or antiplatelet agentsXx_NEWLINE_xXActive major bleedingXx_NEWLINE_xXAny 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* Gross hematuria at the time of randomizationXx_NEWLINE_xXActive bleeding or high risk for bleeding (e.g. known acute gastrointestinal ulcer)Xx_NEWLINE_xXFamilial bleeding diathesisXx_NEWLINE_xXGastrointestinal 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 bleedingXx_NEWLINE_xXPatients 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 excludedXx_NEWLINE_xXHistory of gastric ulcer within the past 5 years (with or without bleeding)Xx_NEWLINE_xXHistory of bleeding disorder or hemorrhagic strokeXx_NEWLINE_xXActive bleeding or otherwise considered high risk for hemorrhage (e.g. known acute gastrointestinal ulcer)Xx_NEWLINE_xXKnown bleeding diathesisXx_NEWLINE_xXEXCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT): Known bleeding disorders (eg, von Willebrand’s disease) or hemophiliaXx_NEWLINE_xXGrade 3 or higher recent (within the past 6 months) or ongoing bleeding eventsXx_NEWLINE_xXHistory of aspirin intolerance, bleeding diathesis, peptic ulcer or gastrointestinal bleed, endoscopic complications, or contraindication to colonoscopyXx_NEWLINE_xXActive bleeding condition (not limited to: thrombocytopenia, hemophilias, potential bleeding lesions, recent trauma or surgery, recent stroke, confirmed intracranial or intraspinal bleeding)Xx_NEWLINE_xXHistory of GI ulcers, chronic GERD, or GI bleeding in the past 5 yearsXx_NEWLINE_xXHistory of a bleeding diathesis or current anticoagulant therapyXx_NEWLINE_xXParticipant has an underlying predisposition to gastrointestinal (GI) or rectal bleeding are considered ineligible for study participationXx_NEWLINE_xXBleeding diathesisXx_NEWLINE_xXBleeding diathesis, hemorrhagic lesions, active bleeding, and other conditions with a high risk for bleedingXx_NEWLINE_xXHistory of a bleeding tendency or current use of Coumadin or other anticoagulantsXx_NEWLINE_xXKnown bleeding disorders that preclude intramuscular injection (e.g., on anticoagulants or thrombocytopenia)Xx_NEWLINE_xXHistory 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 aspirinXx_NEWLINE_xXEvidence of active mucosal or internal bleedingXx_NEWLINE_xXClinically 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)Xx_NEWLINE_xXHistory of gastric ulcer within the past 5 years (with or without bleeding)Xx_NEWLINE_xXHistory of bleeding disorder or hemorrhagic strokeXx_NEWLINE_xXactive, bleeding diathesis;Xx_NEWLINE_xXHistory of bleeding/coagulation problemsXx_NEWLINE_xXactive bleeding or at high risk of bleedingXx_NEWLINE_xXThe patient has a lack of bleeding disorders, andXx_NEWLINE_xXBleeding disorderXx_NEWLINE_xXPatients with or with a history of uncontrolled bleeding diathesisXx_NEWLINE_xXNo history of bleeding diathesisXx_NEWLINE_xXHistory of major bleeding with bronchoscopyXx_NEWLINE_xXMajor 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 bleedingXx_NEWLINE_xXPatient must not have evidence of active bleeding or bleeding diathesisXx_NEWLINE_xXHave a previously diagnosed condition of gum disease this included gingivitis, gingival bleeding and plaqueXx_NEWLINE_xXActive vaginal bleeding requiring packing and emergent radiation therapyXx_NEWLINE_xXLack bleeding disordersXx_NEWLINE_xXKnown inherited or acquired bleeding disorders.Xx_NEWLINE_xXKnown bleeding disorders (e.g., von Willebrand’s disease) or hemophiliaXx_NEWLINE_xXEvidence of mucosal or internal bleeding and/or is platelet transfusion refractoryXx_NEWLINE_xXAcute gastrointestinal (GI) bleedingXx_NEWLINE_xXBleeding disordersXx_NEWLINE_xXAny condition resulting in increased risk of bleeding at biopsy.Xx_NEWLINE_xXHistory of any coagulation, bleeding, or blood disorders (e.g. anemia)Xx_NEWLINE_xXNo known bleeding disordersXx_NEWLINE_xXNo active bleedingXx_NEWLINE_xXNo active bleeding in the post-operative periodXx_NEWLINE_xXActive bleeding or high risk of bleedingXx_NEWLINE_xXHistory or presence of significant bleeding disordersXx_NEWLINE_xXKnown bleeding diathesis or history of abnormal bleeding, or any other known coagulation abnormalities that would contraindicate the tumor biopsy procedure.Xx_NEWLINE_xXBleeding and Thrombosis:Xx_NEWLINE_xXIf active bleeding requiring acute surgical intervention, not eligibleXx_NEWLINE_xXHistory of significant bleeding disorder unrelated to CMLXx_NEWLINE_xXThe 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.Xx_NEWLINE_xXThe patient has a known predisposition for bleeding such as von Willebrand's disease or other such condition.Xx_NEWLINE_xXKnown presence of significant congenital or acquired bleeding disorder unrelated to cancerXx_NEWLINE_xXMucosal or internal bleeding, or platelet transfusion refractoryXx_NEWLINE_xXKnown bleeding diathesis or history of abnormal bleeding, or any other known coagulation abnormalities that would contraindicate the tumor biopsy procedure.Xx_NEWLINE_xXBleeding or thrombotic disorders.Xx_NEWLINE_xXActive bleeding or pathologic condition that carries a high risk of bleedingXx_NEWLINE_xXTumors located in the central chest or other location where bleeding is associated with high morbidityXx_NEWLINE_xXClinically-significant gastrointestinal disorders, such as perforation, gastrointestinal bleeding, or diverticulitis (Parts D and E only).Xx_NEWLINE_xX