Clinically significant or uncontrolled cardiac disease.Xx_NEWLINE_xXClinically significant respiratory disease that requires mechanical ventilation support or 50% oxygen.Xx_NEWLINE_xXUncontrolled or significant cardiovascular disease, clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation, or Torsades des pointes), clinically significant pulmonary disease (such as ? Grade 2 dyspnea, according to CTCAE 4.03)Xx_NEWLINE_xXResearch participants with other clinically significant medical disorders that could compromise their ability to tolerate protocol therapy or would interfere with the study procedures or results historyXx_NEWLINE_xXCurrent evidence of clinically significant corneal or retinal disorder confirmed by ophthalmologic examination.Xx_NEWLINE_xXNo clinically significant infections as judged by the treating investigatorXx_NEWLINE_xXAny significant medical complications related to induction must have resolvedXx_NEWLINE_xXAny significant medical complications related to therapy must have resolvedXx_NEWLINE_xXAll non-hematologic treatment related toxicities that are deemed clinically significant by the treating investigator must have resolved to =< grade 2Xx_NEWLINE_xXRegistration Step 3 – Maintenance: All non-hematologic treatment related toxicities that are deemed clinically significant by the treating investigator must have resolved to =< grade 2Xx_NEWLINE_xXNo signs of clinically significant hearing lossXx_NEWLINE_xXPatients with clinically significant history of any chronic liver disease.Xx_NEWLINE_xXSignificant abnormalities on ECG at ScreeningXx_NEWLINE_xXSubject has clinically significant and uncontrolled major medical condition(s) including but not limited to:Xx_NEWLINE_xXSerious co-morbid medical conditions, including clinically-significant cardiac diseaseXx_NEWLINE_xXUncontrolled (over the last 30 days), clinically significant confounding medical conditionsXx_NEWLINE_xXSubjects who are at significant risk for general anesthesiaXx_NEWLINE_xXElectrocardiogram (ECG) with no clinically significant findings as assessed by the Investigator;Xx_NEWLINE_xXHistory of clinically significant, medically unstable disease which, in the judgment of the investigator, would jeopardize the safety of the subject, interfere with trial assessments or endpoint evaluation, or otherwise impact the validity of the trial results.Xx_NEWLINE_xXImpaired cardiac function or clinically significant cardiac disease.Xx_NEWLINE_xXUncontrolled clinically significant arrhythmias.Xx_NEWLINE_xXImpaired cardiac function or clinically significant cardiac diseaseXx_NEWLINE_xXPatients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that would compromise the patient’s ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or resultsXx_NEWLINE_xXHas a medical history of clinically significant lung diseaseXx_NEWLINE_xXImpaired cardiac function or clinically significant cardiac disease, including any of the following (Criteria a through g):Xx_NEWLINE_xXSignificant history of medical conditions as listed in the protocol.Xx_NEWLINE_xXLaboratory test values at screening outside of the normal range and judged clinically significant by the investigatorXx_NEWLINE_xXSignificant myelofibrosis (>2+fibrosis)Xx_NEWLINE_xXClinically significant anemia due to non-MDS etiologiesXx_NEWLINE_xXClinically significant graft versus host disease (GVHD) or GVHD requiring initiation of treatment or treatment escalation within 21 days, and/or > grade 1 persistent or clinically significant non-hematologic toxicity related to HSCTXx_NEWLINE_xXTreatment with clinically significant metabolic CYP3A inducers within 14 days before the first dose of study drug; clinically significant CYP3A inducers are not permitted during the studyXx_NEWLINE_xXClinically significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation.Xx_NEWLINE_xXClinically significant gastrointestinal disorders.Xx_NEWLINE_xXHistory of clinically significant cardiac dysfunctionXx_NEWLINE_xXKnown clinically significant liver diseaseXx_NEWLINE_xXEvidence or history of other significant, hepatic, renal, ophthalmologic, psychiatric, or gastrointestinal disease which would likely increase the risks of participating in the study.Xx_NEWLINE_xXParticipant has clinically significant uncontrolled conditions.Xx_NEWLINE_xXEvidence of any significant, uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of resultsXx_NEWLINE_xXUrinalysis: o No clinically significant abnormalitiesXx_NEWLINE_xXHistory of clinically significant coagulation or platelet disorder in the past 12 months.Xx_NEWLINE_xXClinically significant cardiac disease.Xx_NEWLINE_xXCurrent diagnosis of any other active or clinically significant nonbreast cancerXx_NEWLINE_xXHistory of clinically significant thrombosis within the past 3 months prior to randomization that, in the investigator's opinion, may place the patient at risk of side effects from anti-angiogenesis products.Xx_NEWLINE_xXHistory of clinically significant glomerulonephritis, biopsy-proven tubulointerstitial nephritis, crystal nephropathy, or other renal insufficiencies.Xx_NEWLINE_xXKnown significant clinically significant gastrointestinal diseaseXx_NEWLINE_xXHistory of clinically significant cardiac dysfunctionXx_NEWLINE_xXClinically significant third-space fluid accumulationXx_NEWLINE_xXImpaired cardiac function or clinically significant cardiac disease.Xx_NEWLINE_xXImpaired cardiac function or clinically significant cardiac diseaseXx_NEWLINE_xXKnown clinically significant liver diseaseXx_NEWLINE_xXEvidence of increased intracranial pressure (clinically significant papilledema, vomiting, and nausea, or reduced level of consciousness)Xx_NEWLINE_xXClinically significant neurologic event (stroke) or any neurological deficit lasting > 24 hours;Xx_NEWLINE_xXHave any clinically significant disease considered by the investigator to interfere with study participationXx_NEWLINE_xXHistory of clinically significant cardiac disease; uncontrolled hypertensionXx_NEWLINE_xXHas clinically significant heart disease that affects normal activities.Xx_NEWLINE_xXClinically significant cardiac diseaseXx_NEWLINE_xXOther clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise participation of the subject in the studyXx_NEWLINE_xXEvidence of clinically significant immunosuppression.Xx_NEWLINE_xXClinically significant acute or unstable cardiovascular, cerebrovascular (stroke), renal, gastrointestinal, pulmonary, immunological, endocrine, or central nervous system disorders.Xx_NEWLINE_xXClinically significant bleeding event, as judged by investigator, within prior 6 monthsXx_NEWLINE_xXClinically significant hearing impairment, as judged by the Principal Investigator.Xx_NEWLINE_xXHistory of thromboembolism within the past 5 years, history of catheter-related thrombophlebitis or other clinically significant thrombophlebitis are excluded.Xx_NEWLINE_xXHistory of clinically significant GI bleed, intestinal obstruction, or GI perforation within 6 months of study doseXx_NEWLINE_xXHistory of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelaeXx_NEWLINE_xXHistory of malabsorption or other clinically significant metabolic dysfunctionXx_NEWLINE_xXHistory of clinically significant cardiac or pulmonary dysfunction as specified in antecedent studyXx_NEWLINE_xXHave had significant active cardiac disease within 6 months prior to the start of study treatment, including any of the following:Xx_NEWLINE_xXHave any other concurrent severe and/or uncontrolled concomitant medical condition that could compromise participation in the study (eg, clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection).Xx_NEWLINE_xXHistory of osteonecrosis of the hip or have evidence of structural bone abnormalities in the proximal femur on MRI scan that are symptomatic and clinically significant.Xx_NEWLINE_xXHistory or presence of an abnormal electrocardiogram (ECG) that is clinically significant in the investigator's opinionXx_NEWLINE_xXSubject has any neuropathy > Grade 1. 5. Subject has impaired cardiac function or clinically significant cardiac diseases, including any of the following:Xx_NEWLINE_xXSignificant screening ECG abnormalities.Xx_NEWLINE_xXAny known clinically significant prior radiation to the chest area that included lung parenchyma.Xx_NEWLINE_xXCardiac ejection fraction >= 45%, no evidence of physiologically significant pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findingsXx_NEWLINE_xXCurrent, clinically significant, active infection that in the opinion of the Investigator would make them an unfit participant in the trialXx_NEWLINE_xXWomen who have had an abnormal gynecology exam within the last three years with clinically significant findings, such as secondary dysmenorrhea, polyps, or atypia, which in the opinion of the Investigator would interfere with the study.Xx_NEWLINE_xXKnown clinically significant liver disease,Xx_NEWLINE_xXHistory or evidence of clinically significant pulmonary disease that precludes the use of general anesthesia.Xx_NEWLINE_xXEXCLUSION - TREATMENT: Clinically significant viral infection or uncontrolled viral reactivation of EBV, CMV, Adv, BK-virus, or HHV-6Xx_NEWLINE_xXClinically significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation.Xx_NEWLINE_xXClinically significant gastrointestinal disordersXx_NEWLINE_xXClinically significant history of liver diseaseXx_NEWLINE_xXHistory or presence of clinically significant ventricular or atrial dysrhythmia >Grade 2 per NCI CTCAE v4.0Xx_NEWLINE_xXPatients with any clinically significant unrelated systemic illness that would compromise the patient’s ability to tolerate protocol therapyXx_NEWLINE_xXClinically significant anemia, neutropenia or thrombocytopenia at screeningXx_NEWLINE_xXPatients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) that will likely interfere with the study procedures or resultsXx_NEWLINE_xXPatients with clinically significant abnormalities on urinalysis at < 14 days prior to randomization.Xx_NEWLINE_xXClinically significant cardiac disease or impaired cardiac functionXx_NEWLINE_xXOther clinically significant comorbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise the patient's participation in the study.Xx_NEWLINE_xXMedically significant (symptomatic) bradycardiaXx_NEWLINE_xXLaboratory parameters for vital functions should be in the normal range or not clinically significant.Xx_NEWLINE_xXSignificant ECG abnormalities.Xx_NEWLINE_xXHistory or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.Xx_NEWLINE_xXHistory of clinically significant cardiac dysfunctionXx_NEWLINE_xXHistory of malabsorption or other clinically significant metabolic dysfunctionXx_NEWLINE_xXHistory of autoimmune disease, clinically significant cardiac or pulmonary dysfunctionXx_NEWLINE_xXHave evidence of active clinically significant bleed (e.g., gastrointestinal bleed, hemoptysis, or gross hematuria) at screeningXx_NEWLINE_xXImpaired cardiac function or clinically significant cardiac disease.Xx_NEWLINE_xXClinically significant active infection, in the judgment of the investigatorXx_NEWLINE_xXHave clinically significant dermatological disorders (e.g., eczema, psoriasis, or any unhealed skin wounds or ulcers) as assessed by the principal investigator during screening and during the studyXx_NEWLINE_xXClinically significant cardiac disease.Xx_NEWLINE_xXPatients with acute or chronic hepatic dysfunction as evidenced by clinically significant abnormalities in albumin, total protein, or prothrombin time, or evidence of hepatic injury with clinically important (> grade 1) changes in AST, ALT, ALP, bilirubin, or GGT values.Xx_NEWLINE_xXThe patient has uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, pulmonary hypertension) that, in the Investigator's opinion, would put the patient at significant risk for pulmonary complications during the study.Xx_NEWLINE_xXClinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months prior to randomization)Xx_NEWLINE_xXKnown or suspected history of significant drug abuse as judged by the InvestigatorXx_NEWLINE_xXSignificant intercurrent illnessXx_NEWLINE_xXCOHORT I: No significant contraindications to cisplatinum chemotherapy (significant hearing loss, renal dysfunction or neuropathy)Xx_NEWLINE_xXActive or clinically significant cardiac disease.Xx_NEWLINE_xXHistory of clinically significant or uncontrolled cardiac disease including but not limited to:Xx_NEWLINE_xXPatient with clinically positive nodal diseaseXx_NEWLINE_xXClinically significant cardiac, respiratory, gastrointestinal, renal, hepatic or neurological conditions.Xx_NEWLINE_xXImpaired cardiac function or clinically significant cardiac disease.Xx_NEWLINE_xXSubject who has a clinically significant coagulation disorder or disease, defined as a platelet count <100,000 per microliter, International Normalized Ratio >1.5, or a PTT more than 1.5 times outside the laboratory's normal reference range;Xx_NEWLINE_xXHas a clinically significant coagulopathy per investigator’s assessmentXx_NEWLINE_xXHistory of clinically significant cardiac dysfunctionXx_NEWLINE_xXPatients with any clinical significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) that is likely to interfere with the study procedures or resultsXx_NEWLINE_xXTaking a medication known to be clinically significant P-gp inhibitors or inducers within 14 days of treatment with Oratecan.Xx_NEWLINE_xXOther clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise participation of the patient in the studyXx_NEWLINE_xXImpaired cardiac function including any of the following:\r\n* Myocardial infarction within 6 months of starting study drug\r\n* A past medical history of clinically significant electrocardiography (ECG) abnormalities, including corrected QT (QTc) 481 ms or greater\r\n* Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)Xx_NEWLINE_xXPatients with a significant other medical conditions that would make them unsuitable for transplantXx_NEWLINE_xXMust have a normal ejection fraction (within the reference range of the institution) and no clinically significant valvular dysfunction.Xx_NEWLINE_xXClinically significant patient history which in the judgment of the principal investigator would compromise the patient’s ability to tolerate high-doseXx_NEWLINE_xXOther serious illnesses or medical conditions including but not limited to:\r\n* Unstable cardiac disease despite treatment, myocardial infarction within 6 months prior to study entry\r\n* History of significant neurologic or psychiatric disorders including dementia or seizures \r\n* Active clinically significant uncontrolled infection \r\n* Active peptic ulcer disease defined as unhealed or clinically active \r\n* Active drug addiction including alcohol, cocaine or intravenous drug use defined as occurring within the 6 months preceding diagnosis \r\n* Chronic obstructive pulmonary disease, defined as being associated with a hospitalization for pneumonia or respiratory decompensation within 12 months of diagnosis; this does not include obstruction from tumor \r\n* Autoimmune disease requiring therapy, prior organ transplant, or known human immunodeficiency virus (HIV) infection\r\n* Interstitial lung disease\r\n* Hepatitis C by history \r\n* Concurrent treatment with any other anticancer therapy\r\n* Participation in an investigational therapeutic drug trial within 30 days of study entryXx_NEWLINE_xXRETREATMENT WITH MODIFIED T-CELLS INCLUSION CRITERIA: Research participant without clinically significant encephalopathy/new focal neurologic deficitsXx_NEWLINE_xXEvidence of increased intracranial pressure (clinically significant papilledema, vomiting and nausea or reduced level of consciousness)Xx_NEWLINE_xXClinically significant, uncontrolled heart diseaseXx_NEWLINE_xXPatient has significant and/or uncontrolled cardiac, renal, hepatic or other systemic disorders or significant psychological conditions at baseline visit that in the investigator’s judgment would jeopardize subject enrollment or compliance with the study proceduresXx_NEWLINE_xXClinically significant pulmonary dysfunction, active infection, prior allogeneic bone marrow transplant, active autoimmune diseaseXx_NEWLINE_xXClinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), which in the judgment of the principal or associate investigator would compromise the patient’s ability to tolerate this therapy or are likely to interfere with the study procedures or resultsXx_NEWLINE_xXNo clinically significant infections as judged by the treating investigatorXx_NEWLINE_xXTREATMENT WITH SJCAR19: Electrocardiogram (EKG) without evidence of clinically significant arrhythmiaXx_NEWLINE_xXEvidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results or that could increase risk to the patient, including renal disease that would preclude chemotherapy administration or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm).Xx_NEWLINE_xXSignificant screening ECG abnormalitiesXx_NEWLINE_xXClinically significant patient history which in the judgment of the principal investigator (PI) would compromise the patients’ ability to tolerate high-dose aldesleukin.Xx_NEWLINE_xXHave electrocardiogram (ECG) with no clinically significant findings as assessed by the investigator performed within 28 days prior to first dose;Xx_NEWLINE_xXSignificant pulmonary disease or conditionXx_NEWLINE_xXImplanted pacemaker, defibrillator or deep brain stimulator, or documented clinically significant arrhythmiasXx_NEWLINE_xXEvidence of increased intracranial pressure (midline shift > 5 mm, clinically significant papilledema)Xx_NEWLINE_xXEvidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results or that could increase risk to the patient, including renal disease that would preclude chemotherapy administration or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)Xx_NEWLINE_xXHistory of clinically significant chronic obstructive pulmonary disease (COPD), asthma, or other chronic lung disease.Xx_NEWLINE_xXSignificant cardiopulmonary dysfunctionXx_NEWLINE_xXKnown clinically significant liver diseaseXx_NEWLINE_xXKnown clinically significant liver diseaseXx_NEWLINE_xXOngoing clinically significant infection at or near the incident lesionXx_NEWLINE_xXParticipants with a history of clinically significant, uncontrolled heart disease and/or repolarization abnormalitiesXx_NEWLINE_xXSTRATUM A: Participants with other clinically significant medical disorders (serious infections or significant cardiac, pulmonary, hepatic, psychiatric, gastrointestinal [GI] disease, or other organ dysfunction) that in the investigator’s judgment could compromise their ability to tolerate or absorb protocol therapy or would interfere with the study procedures or resultsXx_NEWLINE_xXSTRATUM B: Participants with other clinically significant medical disorders (serious infections or significant cardiac, pulmonary, hepatic, psychiatric, GI disease, or other organ dysfunction) that in the investigator’s judgment could compromise their ability to tolerate or absorb protocol therapy or would interfere with the study procedures or resultsXx_NEWLINE_xXSTRATUM C: Participants with other clinically significant medical disorders (serious infections or significant cardiac, pulmonary, hepatic, psychiatric, GI disease, or other organ dysfunction) that in the investigator’s judgment could compromise their ability to tolerate or absorb protocol therapy or would interfere with the study procedures or resultsXx_NEWLINE_xXParticipants may not have current or history of clinically significant muscle disorders (eg, myositis), recent unresolved muscle injury, or any condition known to elevate serum CK levelsXx_NEWLINE_xXOther clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise the patient’s participation in the study.Xx_NEWLINE_xXSignificant gastrointestinal diseaseXx_NEWLINE_xXPatients must not have clinically significant cardiac disease.Xx_NEWLINE_xXClinically significant cardiac diseaseXx_NEWLINE_xXHistory of significant cerebrovascular diseaseXx_NEWLINE_xXSignificant cardiac abnormalitiesXx_NEWLINE_xXConcurrent clinically significant infections as determined by the treating Investigator.Xx_NEWLINE_xXHas clinically significant lung disease or is suspected to have such diseases by imaging at ScreeningXx_NEWLINE_xXHas clinically significant corneal diseaseXx_NEWLINE_xXTreatment with clinically significant metabolic inducers within 14 days before the first dose of study drug; clinically significant metabolic inducers are not permitted during the studyXx_NEWLINE_xXDecompensated liver disease as evidenced by clinically significant ascites refractory to diuretic therapy, hepatic encephalopathy, or coagulopathyXx_NEWLINE_xXCardiac ejection fraction ? 50%, no evidence of pericardial effusion, and no clinically significant arrhythmiasXx_NEWLINE_xXClinically-significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenationXx_NEWLINE_xXPatients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), likely interfere with the study procedures or resultsXx_NEWLINE_xXHistory of clinically significant hemorrhagic or thromboembolic event in the past 6 monthsXx_NEWLINE_xXDocumented clinically significant cardiac arrhythmiasXx_NEWLINE_xXHave a significant cardiac condition.Xx_NEWLINE_xXConcurrent severe and/or uncontrolled medical conditions, which may compromise participation in the study, including impaired heart function or clinically significant heart diseaseXx_NEWLINE_xXClinically significant abnormal laboratory resultsXx_NEWLINE_xXCurrent, serious, clinically significant cardiac arrhythmias as determined by the investigator, or patient receiving a digitalis derivative.Xx_NEWLINE_xXTreatment with clinically significant metabolic enzyme inducers within 14 days before the first dose of the study drug; clinically significant metabolic enzyme inducers are not permitted during this studyXx_NEWLINE_xXThe subject has experienced any of the following:\r\n* Clinically significant gastrointestinal bleeding within 6 months before the first dose of study treatment\r\n* Clinically significant hemoptysis within 3 months of the first dose of study treatment\r\n* Any other signs indicative of pulmonary hemorrhage within 3 months before the start of study treatmentXx_NEWLINE_xXSignificant pulmonary disease or conditionXx_NEWLINE_xXPatients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunctionXx_NEWLINE_xXAll persistent clinically significant toxicities from prior chemotherapy must be less than or equal to grade 1Xx_NEWLINE_xXNo clinically significant infections as judged by the treating investigatorXx_NEWLINE_xXAny clinically significant uncontrolled concomitant diseaseXx_NEWLINE_xXCardiac ejection fraction >= 45%, no evidence of physiologically significant pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findingsXx_NEWLINE_xXIf in Arm G, significant allergic reaction to cisplatin.Xx_NEWLINE_xXCHEMOTHERAPY/CELL INFUSION ELIGIBILITY: Patients with electrocardiogram (EKG) within 14 days of initiation of chemotherapy demonstrating no new significant rhythm, axis or ST segment changes will be included; if clinically significant, new EKG changes are present, patients may be included if cardiac stress test indicates no reversible cardiac ischemiaXx_NEWLINE_xXEvidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome)Xx_NEWLINE_xXHas any other clinically significant abnormal laboratory value in the opinion of the investigatorXx_NEWLINE_xXAcute or chronic, clinically significant hematologic, pulmonary, cardiovascular, or hepatic or renal functional abnormality as determined by the investigator based on medical history, physical examination, electrocardiography (EKG), and/or laboratory screening testXx_NEWLINE_xXActive or clinically significant cardiac diseaseXx_NEWLINE_xXclinically significant cardiac diseaseXx_NEWLINE_xXclinically significant active infectionXx_NEWLINE_xXclinically significant CNS disorderXx_NEWLINE_xXAbnormalities on 12-lead electrocardiogram (ECG) considered by the investigator to be clinical significant.Xx_NEWLINE_xXKnown impaired cardiac function including any of the following:\r\n* History or presence of clinically significant ventricular or atrial tachyarrhythmias;\r\n* Clinically significant resting bradycardia (< 50 beats per minute);\r\n* Myocardial infarction within 1 year of starting study drug;\r\n* Other clinically significant heart disease (e.g., unstable angina, congestive heart failure, or uncontrolled hypertension)Xx_NEWLINE_xXAcute or chronic, clinically significant hematologic, pulmonary, cardiovascular, hepatic renal, and/or other functional abnormality that would jeopardize the health and safety of the participant as determined by the investigator based on medical history, physical examination, laboratory values, and/or diagnostic studiesXx_NEWLINE_xXPatients on every 2, 3 or 4 week systemic therapy programs must be off the treatment program for at least 2, 3, or 4 weeks, respectively, and must have recovered from any clinically significant toxicity experienced; patients on weekly or daily systemic therapy programs and patients receiving radiation must be at least 1 week since treatment and recovered from any clinically significant toxicity experienced; must be at least 4 weeks and have recovered from major surgeryXx_NEWLINE_xXIf present, clinically significant or symptomatic amounts of ascites should be drained prior to Day 1.Xx_NEWLINE_xXSubjects with clinically significant uncontrolled cardiac diseaseXx_NEWLINE_xXClinically significant dry eye or contact lens useXx_NEWLINE_xXPatients with any clinically significant autoimmune disease uncontrolled with treatmentXx_NEWLINE_xXCardiac ejection fraction ? 50%, no evidence of pericardial effusion as determined by an ECHO, and no clinically significant ECG findingsXx_NEWLINE_xXKnown history of clinically significant active COPD, or other moderate-to-severe chronic respiratory illness present within 6 months.Xx_NEWLINE_xXUncontrolled, clinically significant pulmonary disease (for example, chronic obstructive pulmonary disease, pulmonary hypertension, idiopathic pulmonary fibrosis) that in the opinion of the investigator would put the participant at significant risk for pulmonary complications during the studyXx_NEWLINE_xXActive or clinically significant Gastric Antral Vascular Ectasia (GAVE, \watermelon stomach\)Xx_NEWLINE_xXOngoing clinically significant toxicity (Grade 2 or greater) associated with prior treatment (including radiotherapy or surgery).Xx_NEWLINE_xXOther clinically significant co-morbidities, such as uncontrolled pulmonary disease, active CNS disease, active infection, or any other condition that could compromise participation of the participant in the study.Xx_NEWLINE_xXMedically significant (symptomatic) bradycardia.Xx_NEWLINE_xXClinically significant cardiac diseaseXx_NEWLINE_xXOther clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise participation of the patient in the studyXx_NEWLINE_xXPatients with significant malabsorption as determined by the treating physicianXx_NEWLINE_xXSignificant vascular disease or recent peripheral arterial thrombosisXx_NEWLINE_xXTreatment with clinically significant metabolic enzyme inducers within 14 days before the first dose of the study drug; clinically significant metabolic enzyme inducers are not permitted during this study (CYP3A4/5 inducers)Xx_NEWLINE_xXEither clinically positive (N1 only) or clinically negative axillary nodes (N0)Xx_NEWLINE_xXNo clinically significant infections or any other medical condition(s) that render the subject ineligible for high dose IL-2 therapy as judged by the treating investigatorXx_NEWLINE_xXAny clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise the patient’s participation in the studyXx_NEWLINE_xXHas clinically significant toxicities from previous anti-cancer therapy that have not resolved, or have not stabilized at a new baselineXx_NEWLINE_xXOther serious illnesses or medical conditions including but not limited to:\r\n* Unstable cardiac disease despite treatment, myocardial infarction within 6 months prior to study entry\r\n* History of significant neurologic or psychiatric disorders including dementia or seizures\r\n* Active clinically significant uncontrolled infection\r\n* Active peptic ulcer disease defined as unhealed or clinically active\r\n* Hypercalcemia\r\n* Active drug addiction including alcohol, cocaine or intravenous drug use defined as occurring within the 6 months preceding diagnosis\r\n* Chronic obstructive pulmonary disease, defined as being associated with a hospitalization for pneumonia or respiratory decompensation within 12 months of diagnosis; this does not include obstruction from tumor\r\n* Autoimmune disease requiring therapy, prior organ transplant, or human immunodeficiency virus (HIV) infection\r\n* Interstitial lung disease\r\n* Hepatitis C by history, and confirmed by serologyXx_NEWLINE_xXHistory of clinically significant auditory or ocular toxicity with ICTXx_NEWLINE_xXUrinalysis: No clinically significant abnormalitiesXx_NEWLINE_xXPatients with clinically significant cardiomyopathy requiring treatmentXx_NEWLINE_xXHistory of clinically significant hemorrhagic or thromboembolic event in the past 6 monthsXx_NEWLINE_xXPART 1 EXCLUSION CRITERIA: Subjects with concurrent severe and/or uncontrolled concurrent medical conditions that could compromise participation in the study (e.g., chronic medical or psychiatric condition or laboratory abnormality, uncontrolled hypertension and/or diabetes mellitus, clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection (including hepatitis A, B or C, human immunodeficiency virus [HIV] [testing is not mandatory])Xx_NEWLINE_xXPART 2 GROUP 1 EXCLUSION CRITERIA: Subjects with concurrent severe and/or uncontrolled concurrent medical conditions that could compromise participation in the study (e.g., chronic medical or psychiatric condition or laboratory abnormality, uncontrolled hypertension and/or diabetes mellitus, clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection (including hepatitis A, B or C, human immunodeficiency virus [HIV] [testing is not mandatory])Xx_NEWLINE_xXPART 2 GROUP 2A EXCLUSION CRITERIA: Subjects with concurrent severe and/or uncontrolled concurrent medical conditions that could compromise participation in the study (e.g., chronic medical or psychiatric condition or laboratory abnormality, uncontrolled hypertension and/or diabetes mellitus, clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection (including hepatitis A, B or C, human immunodeficiency virus [HIV] [testing is not mandatory])Xx_NEWLINE_xXPART 2 GROUP 3 EXCLUSION CRITERIA: Subjects with concurrent severe and/or uncontrolled concurrent medical conditions that could compromise participation in the study (e.g., chronic medical or psychiatric condition or laboratory abnormality, uncontrolled hypertension and/or diabetes mellitus, clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection (including hepatitis A, B or C, human immunodeficiency virus [HIV] [testing is not mandatory])Xx_NEWLINE_xXNo clinically significant uncontrolled infections as determined by investigatorXx_NEWLINE_xXPatients must not have clinically significant malabsorption syndrome or historyXx_NEWLINE_xXNo clinically significant infections as judged by the treating investigatorXx_NEWLINE_xXUrinalysis: No clinically significant abnormalitiesXx_NEWLINE_xXOther clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise participation of the patient in the studyXx_NEWLINE_xXOther clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise the patient’s participation in the studyXx_NEWLINE_xXClinically significant unrelated systemic illness (including but not limited to active life threatening infection, cardiac or neurologic events, current hospital admission for a coexisting comorbid illness), which would make it impossible for the patient to tolerate re-irradiation or systemic chemotherapy or likely to interfere with the resultsXx_NEWLINE_xXEXCLUSION CRITERIA FOR PATIENTS WITH NSCLC OR TNBC (COHORT B): Patients with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing; those with an FEV1 of =< 65% or DLCO (corrected) < 40% will be excludedXx_NEWLINE_xXEXCLUSION CRITERIA FOR PATIENTS WITH NSCLC OR TNBC (COHORT B): Significant cardiovascular abnormalities as defined by any one of the following: congestive heart failure, clinically significant hypotension, symptomatic coronary artery disease, or a documented ejection fraction of < 45%; any patient with an EF of 45-49% must receive clearance by a cardiologist to be eligible for the trialXx_NEWLINE_xXEXCLUSION CRITERIA FOR TNBC: Patients with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing; those with an FEV1 of =< 65% or DLCO (corrected) < 40% will be excludedXx_NEWLINE_xXEXCLUSION CRITERIA FOR TNBC: Significant cardiovascular abnormalities as defined by any one of the following: congestive heart failure, clinically significant hypotension, symptomatic coronary artery disease or a documented ejection fraction of < 45%; any patient with an EF of 45-49% must receive clearance by a cardiologist to be eligible for the trialXx_NEWLINE_xXHistory or current diagnosis of cardiac disease indicating significant risk of safety for patients participating in the study such as uncontrolled or significant cardiac diseaseXx_NEWLINE_xXComplete blood count (CBC) - no clinically significant findingsXx_NEWLINE_xXComplete metabolic profile (CMP) - no clinically significant findingsXx_NEWLINE_xXLactate dehydrogenase (LDH) - no clinically significant findingsXx_NEWLINE_xXOther clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise participation of the patient in the studyXx_NEWLINE_xXImpaired cardiac function or clinically significant cardiac diseasesXx_NEWLINE_xXUncontrolled or significant cardiovascular disease, clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes), clinically significant pulmonary disease (such as ? Grade 2 dyspnea, according to CTCAE 4.03).Xx_NEWLINE_xXHistory or evidence of other clinically significant disorders that would pose a risk to subject safety.Xx_NEWLINE_xXParticipants with impaired cardiac function or clinically significant cardiac disease.Xx_NEWLINE_xXSignificant organ compromise that will increase risk of toxicity or mortalityXx_NEWLINE_xXUncontrolled clinically significant cardiac arrhythmiaXx_NEWLINE_xXuncontrolled or clinically significant conduction abnormalities; first degree AV block or asymptomatic LAFB/RBBB are eligibleXx_NEWLINE_xXClinically significant increased intracranial pressure (e.g., impending herniation), uncontrolled seizures, or requirement for immediate palliative treatmentXx_NEWLINE_xXPatient with any significant concurrent illnessXx_NEWLINE_xXClinically significant, uncontrolled heart diseases.Xx_NEWLINE_xXConcurrent, clinically significant, active malignancies within 12 months of study enrollmentXx_NEWLINE_xXClinically significant hematemesis or hemoptysis of > 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (such as pulmonary hemorrhage) within 4 weeks of enrollmentXx_NEWLINE_xXClinically significant abnormalities found on an ECG.Xx_NEWLINE_xXClinically significant or uncontrolled cardiac disease.Xx_NEWLINE_xXClinically significant cardiac diseaseXx_NEWLINE_xXClinically disease-free after surgeryXx_NEWLINE_xXInclusion Criteria:\n\n        All Patients (Stages 1 and 2):\n\n          1. The patient is ?18 years old\n\n          2. The patient has an Eastern Cooperative Oncology Group (ECOG) performance score of 0-2\n\n          3. The patient has adequate baseline organ function, including cardiac, renal, and\n             hepatic function:\n\n               -  Left ventricular ejection fraction (LVEF) ? institutional lower limit of normal\n                  as measured by multigated acquisition scan or 2-dimensional (2-D) echocardiogram\n                  within 28 days prior to start of therapy and no clinically significant\n                  abnormalities on a 12-lead electrocardiogram (ECG)\n\n               -  Serum creatinine ?1.5 mg/dL (or ?114 µmol/L)\n\n               -  Serum albumin ?3.2 g/dL (or ?32 g/L) in the absence of receipt of (IV) albumin\n                  within the previous 72 hours\n\n               -  Bilirubin ?1.5 mg/dL (or ?26 µmol/L)\n\n               -  Aspartate transaminase (AST) and alanine transaminase (ALT) ?2.5 times the upper\n                  limit of normal (ULN)\n\n               -  CPK ?2.5 times the ULN\n\n          4. If a woman of child bearing potential, the patient has a negative serum or urine\n             pregnancy test within 1 week prior to SL-401 treatment (intervals shorter than 1 week\n             are acceptable, if required by institutional guidelines)\n\n          5. The patient has signed informed consent prior to initiation of any study-specific\n             procedures or treatment\n\n          6. The patient is able to adhere to the study visit schedule and other protocol\n             requirements, including follow-up for response assessments\n\n          7. The patient agrees to use acceptable contraceptive methods for the duration of time in\n             the study, and to continue to use acceptable contraceptive methods for 2 months after\n             the last SL-401 infusion\n\n          8. Patient has an absolute neutrophil count (ANC) ?0.5×10?/L\n\n        Additional Inclusion Criteria Specific to Patients with MF and CMML (Stages 1 and 2)\n\n        Exclusion Criteria:\n\n        All Patients (Stages 1 and 2):\n\n          1. Patient has persistent clinically significant toxicities Grade ?2 from previous\n             chemotherapy not readily controlled by supportive measures (excluding alopecia,\n             nausea, and fatigue)\n\n          2. Patient has received treatment with chemotherapy, wide-field radiation, or biologic\n             therapy within 14 days of study entry\n\n          3. Patient has received treatment with another investigational agent within 14 days of\n             study entry or concurrent treatment with another investigational agent.\n\n          4. Patient has previously received treatment with SL-401 or has a known hypersensitivity\n             to any components of the drug product\n\n          5. Patient has an active malignancy and/or cancer history (excluding myeloproliferative\n             disorders and concomitant myeloid malignancies as specified in the inclusion criteria)\n             that can confound the assessment of the study endpoints. Patients with a past cancer\n             history (within 2 years of entry) and/or ongoing active malignancy or substantial\n             potential for recurrence must be discussed with the Sponsor before study entry.\n             Patients with the following neoplastic diagnoses are eligible: non-melanoma skin\n             cancer, carcinoma in situ (including superficial bladder cancer), cervical\n             intraepithelial neoplasia, or organ-confined prostate cancer with no evidence of\n             progressive disease\n\n          6. Patient has clinically significant cardiovascular disease (e.g., uncontrolled or any\n             New York Heart Association Class 3 or 4 congestive heart failure, uncontrolled angina,\n             history of myocardial infarction or stroke within 6 months of study entry,\n             uncontrolled hypertension or clinically significant arrhythmias not controlled by\n             medication)\n\n          7. Patient has uncontrolled, clinically significant pulmonary disease (e.g., chronic\n             obstructive pulmonary disease, pulmonary hypertension) that, in the Investigator's\n             opinion, would put the patient at significant risk for pulmonary complications during\n             the study\n\n          8. Patient has known active or suspected disease involvement of the central nervous\n             system (CNS). If suspected due to clinical findings, CNS disease should be ruled out\n             with relevant imaging and/or examination of cerebrospinal fluid\n\n          9. Patient is receiving immunosuppressive therapy, with the exception of corticosteroids\n             as specified in the inclusion criteria and tacrolimus, for treatment or prophylaxis of\n             graft-versus-host disease (GVHD). If the patient has been on immunosuppressive\n             treatment or prophylaxis for GVHD, the treatment(s) must have been discontinued at\n             least 14 days prior to study drug and there must be no evidence of Grade ?2 GVHD\n\n         10. Patient has uncontrolled intercurrent illness including, but not limited to,\n             uncontrolled infection, disseminated intravascular coagulation, or psychiatric illness\n             that would limit compliance with study requirements\n\n         11. Patient is pregnant or breast feeding\n\n         12. Patient has known human immunodeficiency virus (HIV)\n\n         13. Patient has evidence of active or chronic Hepatitis B or Hepatitis C infection.\n\n         14. Patient is oxygen-dependent\n\n         15. Patient has any medical condition that in the Investigator's opinion place the patient\n             at an unacceptably high risk for toxicities\n\n        Additional Exclusion Criteria Specific to Patients with MF and CMML (Stages 1 and 2)Xx_NEWLINE_xXClinically significant medical disorders that could compromise the ability to tolerate protocol therapy or that would interfere with the study procedures or results historyXx_NEWLINE_xXSubject has a clinically significant uncontrolled condition(s) s described in the protocol.Xx_NEWLINE_xXARM B COHORT 3: Patients must not have active clinically significant hemoptysisXx_NEWLINE_xXSubject has a clinically significant peripheral artery disease, e.g., those with claudication, within 6 monthsXx_NEWLINE_xXClinically significant peripheral vascular disease or vascular disease (including aortic aneurysm or aortic dissection)Xx_NEWLINE_xXPatients must have recovery from other clinically significant, non-hematologic toxicities to =< grade 2Xx_NEWLINE_xXHas any clinically significant infectionXx_NEWLINE_xXAcute or chronic, clinically significant hematologic, pulmonary, cardiovascular, or hepatic or renal functional abnormality as determined by the investigator based on medical history, physical examination, electrocardiogram (EKG), and/or laboratory screening testXx_NEWLINE_xXPatients with clinically significant unrelated systemic illness (including autoimmune disease, serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) which in the judgment of the principal or associate investigators would compromise the patient’s ability to tolerate this therapy or are likely to interfere with the study procedures or resultsXx_NEWLINE_xXClinically significant peripheral vascular diseaseXx_NEWLINE_xXRETREATMENT WITH MODIFIED T CELLS: Research participant without clinically significant encephalopathy/ new focal neurologic deficitsXx_NEWLINE_xXPatients with clinically significant increased intracranial pressure (e.g., impending herniation), uncontrolled seizures, or requirement for immediate palliative treatmentXx_NEWLINE_xXHistory of clinically significant hemorrhagic or thromboembolic event in the past 6 monthsXx_NEWLINE_xXknown pneumonitis or pulmonary fibrosis with clinically significant impairment of pulmonary functionXx_NEWLINE_xXSignificant organ dysfunction defined as:Xx_NEWLINE_xXAcute or chronic, clinically significant hematologic, pulmonary, cardiovascular, or hepatic or renal functional abnormality as determined by the investigator based on medical history, physical examination, electrocardiogram (EKG), and/or laboratory screening testXx_NEWLINE_xXClinically significant uncontrolled illnessXx_NEWLINE_xXPatients with any clinically significant autoimmune disease uncontrolled with treatmentXx_NEWLINE_xXResearch participant without clinically significant encephalopathy/new focal deficitsXx_NEWLINE_xXImpaired cardiac function or clinically significant heart disease, including any one of the following:\r\n* Angina pectoris within 3 months\r\n* Acute myocardial infarction within 3 months\r\n* Corrected QT interval (QTc) > 480 msec on the screening electrocardiogram (ECG)\r\n* A past medical history of clinically significant ECG abnormalities\r\n* Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)Xx_NEWLINE_xXResearch participants without clinically significant encephalopathy/new focal deficitsXx_NEWLINE_xXResearch participant without clinically significant encephalopathy/new focal deficitsXx_NEWLINE_xXNeurological: research participant without clinically significant encephalopathy/new focal deficitsXx_NEWLINE_xXClinically no evidence of pulmonary diseaseXx_NEWLINE_xXClinically significant heart diseaseXx_NEWLINE_xXImpaired cardiac function or clinically significant heart disease, including any one of the following:\r\n* Angina pectoris within 3 months\r\n* Acute myocardial infarction within 3 months\r\n* Fridericia QT (QTcF) > 450 msec for males and > 470 msec for females on the screening electrocardiogram (ECG)\r\n* A past medical history of clinically significant ECG abnormalities or a family history of prolonged QT-interval syndrome\r\n* Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)Xx_NEWLINE_xXPatients must not have nor had active or recent peptic ulcer disease within the past 6 months\r\n* Patients with active significant symptoms of dyspepsia will be excludedXx_NEWLINE_xXActive infection or antibiotics within 48 hours prior to study enrollment, including unexplained fever (temp > 38.1°C), if deemed clinically significant by the treating physician.Xx_NEWLINE_xXClinically significant gastrointestinal disordersXx_NEWLINE_xXClinically significant abnormalities in laboratory test results (including complete blood count, chemistry panel including electrolytes, and urinalysis)Xx_NEWLINE_xXSignificant risk of suicide based on the investigator’s judgmentXx_NEWLINE_xXClinically significant coagulation disorderXx_NEWLINE_xXClinically significant peripheral vascular diseaseXx_NEWLINE_xXPatients with any amount of clinically significant pericardial effusionXx_NEWLINE_xXClinically significant comorbid disease or other underlying condition, including major autoimmune disorders that would contraindicate study therapy or confuse interpretation of study resultsXx_NEWLINE_xXSubjects must not have a history of any significant renal or hepatic disease requiring ongoing medical therapy or clinical interventionXx_NEWLINE_xXClinical evidence of significant renal impairmentXx_NEWLINE_xXPatient with evidence of clinically significant bradycardia (heart rate [HR] < 50), or a history of clinically significant bradyarrhythmias such as sick sinus syndrome, 2nd degree atrioventricular (AV) block (Mobitz type 2), patient with uncontrolled hypertension (>= 140/90 mmHg). Patients who are controlled on antihypertensive medication will be allowed to enter the studyXx_NEWLINE_xXHistory of clinically significant coagulopathyXx_NEWLINE_xXClinically significant comorbid disease or other underlying condition, including major autoimmune disorders that would contraindicate study therapy or confuse interpretation of study resultsXx_NEWLINE_xXClinically significant systemic illness (e.g. serious active infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the judgment of the principal investigator (PI) would compromise the patient’s ability to tolerate protocol therapy or significantly increase the risk of complicationsXx_NEWLINE_xXPatients with clinically significant unexplained bleeding within 28 days prior to entering the studyXx_NEWLINE_xXPatients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the patient’s ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or resultsXx_NEWLINE_xXHistory of clinically significant ventricular arrhythmiasXx_NEWLINE_xXHistory of clinically significant (as determined by the treating physician) atrial arrhythmia;Xx_NEWLINE_xXHistory or evidence of clinically significant pulmonary disease that precludes the use of general anesthesia.Xx_NEWLINE_xXClinically significant cardiac disease or impaired cardiac function, including any of the following:Xx_NEWLINE_xXHave clinically significant graft versus host disease (GVHD), or GVHD requiring initiation or escalation of treatment within the last 21 daysXx_NEWLINE_xXRespiratory Function: Adequate respiratory function in the opinion of the Investigator with no clinically significant uncontrolled respiratory disease.Xx_NEWLINE_xXConcurrent or Intercurrent Illness: Impaired wound healing due to diabetes; Significant concurrent or intercurrent illness, psychiatric disorders or alcohol or chemical dependence that would compromise Subject safety or compliance or interfere with interpretation of the study; Uncontrolled thyroid disease or cystic fibrosis; Presence of clinically significant acute or unstable cardiovascular, cerebrovascular (stroke), renal, gastrointestinal, pulmonary, immunological (with the exception of the presence of hepatitis B virus (HBV), viral hepatitis, or cirrhosis), endocrine, or central nervous system disorders; Current encephalopathy or current treatment for encephalopathy; Variceal bleeding requiring hospitalization or transfusion within 4 months of screening; History of human immunodeficiency virus or acquired immune deficiency syndrome; The clinical presence of ascites.Xx_NEWLINE_xXSerum bilirubin =< 2 x ULN or considered not clinically significantXx_NEWLINE_xXElectrocardiography (EKG) without evidence of ischemia or significant arrhythmiaXx_NEWLINE_xXHistory of hepatic disease or significant hepatic dysfunctionXx_NEWLINE_xXSubjects at significant risk for general anesthesiaXx_NEWLINE_xXSubjects with uncontrolled (over the last 30 days) clinically significant confounding medical conditionsXx_NEWLINE_xXEvidence of clinically significant neuropathy (> Grade 1) by physical exam.Xx_NEWLINE_xXHistory of clinically significant cardiac diseaseXx_NEWLINE_xXClinically significant iron metabolism disorders (eg, sickle cell anemia)Xx_NEWLINE_xXAny Grade 3 or higher lab abnormalities should be discussed and approved by the Medical Monitor prior to enrollment (even if not considered clinically significant);Xx_NEWLINE_xXSignificant pulmonary disease or conditionXx_NEWLINE_xXSignificant cardiac abnormalities;Xx_NEWLINE_xXSignificant laboratory abnormalities;Xx_NEWLINE_xXClinically significant medical history or ongoing chronic illness that would jeopardize the safety of the participant or compromise the quality of the data derived from his/her participation in this studyXx_NEWLINE_xXTreatment with clinically significant metabolic enzyme inducers within 14 days before the first dose of the study drug; clinically significant metabolic enzyme inducers are not permitted during this studyXx_NEWLINE_xXSymptomatic, clinically significant autonomic neuropathy which the Principal Investigator (PI) feels will preclude administration of study treatmentXx_NEWLINE_xXHas clinically significant corneal diseaseXx_NEWLINE_xXClinically significant, uncontrolled heart diseasesXx_NEWLINE_xXElectrocardiogram (EKG) without clinically significant abnormalityXx_NEWLINE_xXClinically significant abnormality on ophthalmologic examination during screening evaluationXx_NEWLINE_xXClinically significant, uncontrolled heart diseases.Xx_NEWLINE_xXClinically normal resting 12-lead ECG at screening visit or, if abnormal, considered not clinically significant by the PIXx_NEWLINE_xXClinically normal resting 12-lead ECG at screening visit or, if abnormal, considered not clinically significant by the PIXx_NEWLINE_xXEvidence of clinically significant pancreatitis as determined by the investigatorXx_NEWLINE_xXAny significant ophthalmologic abnormalityXx_NEWLINE_xXPatients who have impaired cardiac function or clinically significant cardiac diseases,Xx_NEWLINE_xXClinically significant GVHD or organ dysfunction where chemotherapy specified by protocol cannot be givenXx_NEWLINE_xXUrinalysis: No clinically significant abnormalities.Xx_NEWLINE_xXHave significant baseline neuropathiesXx_NEWLINE_xXClinically significant abnormal 12-lead ECG findings;Xx_NEWLINE_xXcurrent, serious, clinically significant cardiac arrhythmias as determined by the Investigator.Xx_NEWLINE_xXScreening ECG abnormality documented by the investigator as medically significantXx_NEWLINE_xXKnown history of clinically significant active COPD, or other moderate-to-severe chronic respiratory illness present within 6 months.Xx_NEWLINE_xXNo clinically significant infections as judged by the treating investigatorXx_NEWLINE_xXPatients with history of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae are NOT eligible for the studyXx_NEWLINE_xXSignificant medical disease other than cancerXx_NEWLINE_xXHistory of significant neurologic or psychiatric disorders including dementia or seizuresXx_NEWLINE_xXSignificant medical disease other than cancerXx_NEWLINE_xXPatients with significant intercurrent illnesses.Xx_NEWLINE_xXAny significant diseases (other than HL) or clinically significant findings, including psychiatric and behavioral problems, medical history and/or physical examination findings that would preclude the subject from participating in the studyXx_NEWLINE_xXClinically significant systemic disease, as determined by the investigator, which could affect study participation or study resultsXx_NEWLINE_xXClinically significant anemia according to investigator's assessment due to factors such as iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis or gastrointestinal bleeding.Xx_NEWLINE_xX-  Participant has clinically significant uncontrolled condition(s) as described in the protocol.Xx_NEWLINE_xXClinically significant graft versus host disease (GVHD) or active GVHD requiring initiation or escalation of treatment within 28-day screening period.Xx_NEWLINE_xXClinically significant coagulation abnormality, such as disseminated intravascular coagulation.Xx_NEWLINE_xXClinically significant surgery within 2 weeks of enrollment.Xx_NEWLINE_xXHas persistent, clinically significant > Grade 1 non-hematologic toxicity from prior AML therapiesXx_NEWLINE_xXSignificant gastrointestinal abnormality.Xx_NEWLINE_xXClinically significant cardiac disease as per protocol-defined criteria.Xx_NEWLINE_xXActive clinically significant infectionXx_NEWLINE_xXKnown history of clinically significant active COPD, or other moderate-to-severe chronic respiratory illness present within 6 months.Xx_NEWLINE_xXCardiac ejection fraction >= 50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findingsXx_NEWLINE_xXCardiac ejection fraction >= 40%, and no clinically significant electrocardiogram (ECG) findings.Xx_NEWLINE_xXActive clinically significant infection within 7-days of study treatment.Xx_NEWLINE_xXPatients taking medications with known significant drug interactionsXx_NEWLINE_xXElectrocardiography (ECG) without evidence of clinically significant arrhythmia or ischemia.Xx_NEWLINE_xXPresence of clinically significant increased intracranial pressure (e.g. impending herniation) or hemorrhage, uncontrolled seizures, or requirement for immediate palliative treatment.Xx_NEWLINE_xXHistory or evidence of current clinically significant uncontrolled arrhythmiasXx_NEWLINE_xXPatients with history of clinically significant venous thromboembolismXx_NEWLINE_xXClinically significant toxicities from prior chemotherapy must not be greater than grade 1Xx_NEWLINE_xXConcurrent Illness\r\n* Patients with any clinically significant unrelated systemic illness (serious infections grade >= 2 or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the patient’s ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results\r\n* Patients with a history of any other malignancy, except patients with a secondary brain tumor if the patient’s first malignancy has been in remission for at least 5 years from the end of treatmentXx_NEWLINE_xXHave had significant active cardiac disease within 6 months prior to the start of study treatmentXx_NEWLINE_xXHave clinically significant cardiac diseaseXx_NEWLINE_xXKnown, clinically significant carotid artery diseaseXx_NEWLINE_xXAny clinically significant electrolyte imbalance, particularly hypokalemia and hypomagnesemia, should be corrected before treatmentXx_NEWLINE_xXClinically significant malabsorption syndromeXx_NEWLINE_xXClinically significant hypersensitivity to denosumab or any components of denosumab 120 mgXx_NEWLINE_xXClinically-significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation.Xx_NEWLINE_xXImpaired cardiac function or clinically significant cardiac diseaseXx_NEWLINE_xXAny significant medical complications related to induction must have resolvedXx_NEWLINE_xXSubjects at significant risk with general anesthesiaXx_NEWLINE_xXSubjects with uncontrolled (over the last 30 days) clinically significant confounding medical conditionsXx_NEWLINE_xXARM B: Patients must not have clinically significant ascites and/or portal vein thrombosisXx_NEWLINE_xXUncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease [COPD], pulmonary hypertension) that in the opinion of the investigator would put the patient at significant risk for pulmonary complications during the studyXx_NEWLINE_xXProgression of disease on the most recent restaging scan or clinically significant disease at the time of evaluation justifying enrolment in a trial in the opinion of the treating physicianXx_NEWLINE_xXClinically significant systemic illness (e.g. serious active infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the judgment of the principal investigator (PI) would compromise the patient’s ability to tolerate protocol therapy or significantly increase the risk of complicationsXx_NEWLINE_xXClinically significant gastrointestinal (GI) disorders, including history of small bowel obstruction unless the obstruction was a surgically treated remote episodeXx_NEWLINE_xXUncontrolled and clinically significant disease-related metabolic disorderXx_NEWLINE_xXClinically significant malabsorption syndromeXx_NEWLINE_xXThe subject has experienced clinically-significant hematemesis or hemoptysis of > 0.5 teaspoon of red blood, or other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatmentXx_NEWLINE_xXPatients must not have clinically significant autoimmune disease that requires treatment with immunosuppressant medicationsXx_NEWLINE_xXPatients with a history of clinically significant venous thromboembolism will be excludedXx_NEWLINE_xXHas a history of significant congestive heart failure or significant pulmonary diseaseXx_NEWLINE_xXSubjects with significant cardiac issuesXx_NEWLINE_xXSubjects with history of anaphylaxis or angioedema, bronchial asthma, peptic ulcer\n             and clinically significant food or drug allergyXx_NEWLINE_xXMagnesium >= within institutional normal limits, or =< grade 1 according to NCI-CTCAE version 4.03 if judged clinically not significant by the investigatorXx_NEWLINE_xXAny clinically significant active infection that requires systemic treatment at the time of enrollmentXx_NEWLINE_xXAny other concurrent severe and/or uncontrolled concomitant medical condition that could compromise participation in the study - e.g., clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infectionXx_NEWLINE_xXSubjects with a history of significant hemoptysis per the treating physician's judgment, cerebral hemorrhage or clinically significant gastrointestinal (GI) hemorrhage or myocardial infarction (MI) within the past 6 monthsXx_NEWLINE_xXClinically significant sensorineural hearing impairment which may be worsened via cisplatin exposure (audiometric abnormalities without corresponding clinical deafness are not grounds for exclusion)Xx_NEWLINE_xXHas a clinically significant coagulopathy per investigator’s assessmentXx_NEWLINE_xXPatients on every 2, 3, or 4 week systemic treatment programs must be off the treatment program at least 2, 3, or 4 week, respectively, and must have recovered from any clinically significant toxicity experienced; patients on weekly or daily systemic treatment programs and patients receiving radiation must be off at least 1 week and must have recovered from any clinically significant toxicity experienced; must be at least 4 weeks and have recovered from major surgeryXx_NEWLINE_xXClinically significant resting bradycardiaXx_NEWLINE_xXClinically significant systemic illness (e.g., serious active infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the judgment of the principal investigator (PI) would compromise the patient’s ability to tolerate protocol therapy or significantly increase the risk of complications; peripheral nerve symptoms from prior therapies or from tumor compression > grade 1Xx_NEWLINE_xXTreatment for clinically-significant hyperglycemia, hyperlipidemia, or hypertension that develops on study is requiredXx_NEWLINE_xXHistory of clinically significant allergic reaction attributed to any injected\n             compound.Xx_NEWLINE_xXSustained or clinically significant cardiac arrhythmiasXx_NEWLINE_xXClinically significant peripheral vascular diseaseXx_NEWLINE_xXClinically significant systemic illness (e.g. serious active infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the judgment of the PI would likely compromise the patient’s ability to tolerate protocol therapy or significantly increase the risk of complicationsXx_NEWLINE_xXClinically significant uncontrolled condition(s).Xx_NEWLINE_xXClinically significant and unexplained elevated liver or renal function testsXx_NEWLINE_xXCurrent or history of clinically significant muscle disorders (e.g., myositis), recent unresolved muscle injury, or any condition known to elevate serum CK levelsXx_NEWLINE_xXPatients with abnormal serum chemistry values, which in the opinion of the Investigator is considered to be clinically significant, will be excluded from the studyXx_NEWLINE_xXSubject has clinically significant abnormality of coagulation profile, such as disseminated intravascular coagulation (DIC).Xx_NEWLINE_xXSubject has active clinically significant GVHD or is on treatment with systemic corticosteroids for GVHD.Xx_NEWLINE_xXSubjects must not have clinically active cerebral metastases.Xx_NEWLINE_xXClinically significant graft versus host disease (GVHD) or GVHD requiring initiation of treatment or treatment escalation within 21 days, and/or > Grade 1 persistent or clinically significant non hematologic toxicity related to HSCT.Xx_NEWLINE_xXClinically significant coagulation abnormality, such as disseminated intravascular coagulation.Xx_NEWLINE_xXThe participant has bowel obstruction or history of chronic diarrhea that is considered clinically significant.Xx_NEWLINE_xXSecond primary malignancy that is clinically detectable or clinically significant at the time of consideration for study enrollmentXx_NEWLINE_xXHas had clinically diagnosed hepatic encephalopathy in the last 6 months.Xx_NEWLINE_xXSignificant co-morbid condition or disease which in the judgment of the Investigator would place the subject at undue risk or interfere with the study; examples include, but are not limited to, cirrhotic liver disease, sepsis, recent significant traumatic injury, and other conditionsXx_NEWLINE_xXSubjects who have plasma cell leukemia or clinically significant amyloidosisXx_NEWLINE_xXClinically localized disease (?T2a) andXx_NEWLINE_xXAny other clinically significant medical condition and/or organ dysfunction that will interfere with the administration of the therapy according to this protocol.Xx_NEWLINE_xXClinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, or clinically significant cardiac arrhythmiasXx_NEWLINE_xXClinically significant respiratory disease that requires mechanical ventilation support or 50% oxygen.Xx_NEWLINE_xXImpaired cardiac function or clinically significant cardiac diseaseXx_NEWLINE_xXClinically significant organ/system disease unrelated to RCC that in the judgment of the investigator should preclude treatment with dalantercept or axitinib.Xx_NEWLINE_xXSignificant immunosuppression.Xx_NEWLINE_xXEvidence of active tuberculosis or recent (<1 week prior to first scheduled dosing) clinically significant infection requiring systemic therapy.Xx_NEWLINE_xXSignificant history or risk of cardiac diseaseXx_NEWLINE_xXPatients must have a baseline electrocardiogram (ECG) performed within 42 days of registration that is normal or considered not clinically significant by the site investigatorXx_NEWLINE_xXHas clinically significant cardiac diseaseXx_NEWLINE_xXSignificant immunosuppression from:Xx_NEWLINE_xXKnown clinically significant liver diseaseXx_NEWLINE_xXClinically significant third-space fluid accumulationXx_NEWLINE_xXThe patient has uncontrolled, clinically significant pulmonary disease (e.g., COPD, pulmonary hypertension) that in the opinion of the investigator would put the patient at significant risk for pulmonary complications during the study.Xx_NEWLINE_xXConcurrent severe and/or uncontrolled medical conditions which may compromise participation in the study, including impaired heart function or clinically significant heart diseaseXx_NEWLINE_xXUrinalysis: No clinically significant abnormalities.Xx_NEWLINE_xXHas a medical history of clinically significant lung diseaseXx_NEWLINE_xXClinically significant unrelated illness which would, in the judgment of the treating physician, compromise the patient's ability to tolerate the investigational agent or be likely to interfere with the study procedures or results.Xx_NEWLINE_xXHistory of clinically significant or uncontrolled cardiac, hepatic, or pulmonary diseaseXx_NEWLINE_xXSubjects with uncontrolled and significant inter-current illness.Xx_NEWLINE_xXAny prior (within 1 year) or current clinically significant ascites as measured by physical examination and that requires paracentesis for control;Xx_NEWLINE_xXClinically significant ascitesXx_NEWLINE_xXClinically significant heart diseaseXx_NEWLINE_xXKnown clinically significant liver diseaseXx_NEWLINE_xXECG without evidence of clinically significant arrhythmia or ischemia.Xx_NEWLINE_xXSignificant immunosuppression from:Xx_NEWLINE_xXDecompensated liver disease as evidenced by clinically significant ascites refractory to diuretic therapy, hepatic encephalopathy, or coagulopathyXx_NEWLINE_xXSignificant active cardiac disease within the previous 6 monthsXx_NEWLINE_xXHas all prior treatment (i.e., chemotherapy, immunotherapy, radiotherapy) related clinically significant toxicities resolve to ? Grade 1 per NCI CTCAE, Version 4.03 or are clinically stable and not clinically significant, at time of consentXx_NEWLINE_xXHas a clinically significant gastrointestinal (GI) abnormality including:Xx_NEWLINE_xXSignificant active cardiac disease within the previous 6 months prior to signing the ICF, including:Xx_NEWLINE_xXSignificant cardiac arrhythmiaXx_NEWLINE_xXsignificant fatigueXx_NEWLINE_xXHas clinically significant cardiac diseaseXx_NEWLINE_xXNo clinically significant progression outside of the CNS on most recent EGFR inhibitor therapyXx_NEWLINE_xXPatients who have received treatment with clinically significant enzyme inducers within 14 days prior to registration are not eligibleXx_NEWLINE_xXECG without evidence of clinically significant arrhythmia or ischemiaXx_NEWLINE_xXSignificant immunosuppression from:Xx_NEWLINE_xXClinically significant cardiac diseaseXx_NEWLINE_xXAny prior or current clinically significant ascitesXx_NEWLINE_xXPatients must not have clinically significant anemia resulting from iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis, or gastrointestinal bleedingXx_NEWLINE_xXHas all prior treatment (i.e., chemotherapy, immunotherapy, radiotherapy) related clinically significant toxicities resolve to ? Grade 1 per CTCAE, version 4.03 or are clinically stable and not clinically significant, at time of enrollmentXx_NEWLINE_xXclinically significant symptomatic arrhythmia despite anti-arrhythmic therapy.Xx_NEWLINE_xXEvidence of any significant, uncontrolled concomitant diseaseXx_NEWLINE_xXSignificant serum chemistry abnormalitiesXx_NEWLINE_xXClinically significant cardiac diseaseXx_NEWLINE_xXInclusion Criteria:\n\n        Adults (aged ? 18 years)\n\n        Histologically confirmed diagnosis of a B-cell lymphoma that has progressed in spite of\n        prior treatment, and for which additional effective standard therapy is not available\n\n        Eastern Cooperative Oncology Group (ECOG) performance status ? 2\n\n        Adequate hematological, renal, hepatic, and coagulation laboratory assessments\n\n        Must give written informed consent to participate in this study before the performance of\n        any study-related procedure\n\n        Exclusion Criteria:\n\n        A primary lymphoma of the central nervous system (CNS) or known lymphomatous involvement of\n        the CNS\n\n        Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the\n        absorption of CPI-1205, including any unresolved nausea, vomiting, or diarrhea that is\n        CTCAE grade >1\n\n        Treatment with proton pump inhibitors, H2 antagonists, or antacids\n\n        Achlorhydria, either documented or suspected on the basis of an associated disease (e.g.,\n        pernicious anemia, atrophic gastritis, or certain gastric surgical procedures)\n\n        Impaired cardiac function or clinically significant cardiac diseases, including any of the\n        following:\n\n          -  Acute myocardial infarction or angina pectoris ? 6 months prior to starting study drug\n\n          -  New York Heart Association Class III or IV congestive heart failure\n\n          -  QTcF > 470 msec on the screening ECG\n\n        Uncontrolled cardiac arrhythmia (patients with rate-controlled atrial fibrillation are not\n        excluded)\n\n        A past medical history of other clinically significant cardiovascular disease (e.g.,\n        uncontrolled hypertension, history of labile hypertension or history of poor compliance\n        with an antihypertensive regimen)\n\n        Any other concurrent severe and/or uncontrolled concomitant medical condition that could\n        compromise participation in the study (e.g., clinically significant pulmonary disease,\n        clinically significant neurological disorder, active or uncontrolled infection)\n\n        Systemic anti-cancer treatment or radiotherapy less than 2 weeks before the first dose of\n        CPI 1205\n\n        Radioimmunotherapy (e.g., 131I-tositumomab, 90Y-ibritumomab tiuxetan) less than 6 weeks\n        before the first dose of CPI-1205\n\n        Treatment with an investigational small molecule less than 2 weeks before the first dose of\n        CPI-1205.\n\n        Treatment with a therapeutic antibody less than 4 weeks before the first dose of CPI-1205.\n\n        Treatment with medications that are strong inhibitors of CYP3A4\n\n        Treatment with medications that are inducers of CYP3A4 enzymes\n\n        Treatment with medications that are known to carry a risk of Torsades de Pointes\n\n        Pregnant or lactating women\n\n        Women of child bearing potential and men with reproductive potential, if they are unwilling\n        to use adequate contraception while on study therapy and for 3 months thereafter\n\n        Patients unwilling or unable to comply with this study protocolXx_NEWLINE_xXMedical conditions that would prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures such as the presence of other clinically significant cardiac, respiratory, gastrointestinal, renal, hepatic or neurological disease.Xx_NEWLINE_xXSignificant active cardiac disease within the previous 6 months from the signing of the ICD, including:Xx_NEWLINE_xXClinically significant cardiac or pulmonary dysfunctionXx_NEWLINE_xXClinically significant peripheral vascular diseaseXx_NEWLINE_xXPatient has no clinically significant abnormalities on urinalysis results.Xx_NEWLINE_xXHave a 12-lead Electrocardiogram (ECG) that is not clinically significant at screening, as determined by the investigatorXx_NEWLINE_xXHave ongoing clinically significant adverse event(s) due to prior treatments administered as determined by the investigator.Xx_NEWLINE_xXSignificant active cardiac disease within the previous 6 months, including:Xx_NEWLINE_xXSubject with an unhealed surgical wound or other clinically significant woundXx_NEWLINE_xXImpaired cardiac function or clinically significant cardiac diseases, including any of the following:Xx_NEWLINE_xXAny other concurrent severe and/or uncontrolled concomitant medical condition that could compromise participation in the study (e.g., clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection)Xx_NEWLINE_xXClinically significant, uncontrolled heart disease and/or recent cardiac repolarization abnormality including any of the following:Xx_NEWLINE_xXEvidence of pulmonary insufficiency or clinically evident chronic obstructive pulmonary diseaseXx_NEWLINE_xXImpaired cardiac function or clinically significant cardiac diseases, including any of the following:Xx_NEWLINE_xXClinically significant hypercalcemia (including vomiting, dehydration and neurological symptoms)Xx_NEWLINE_xXA histologically proven, clinically significant lesion visible on mpMRI (magnetic resonance imaging) that is accessible to PRX302 transperineal injection.Xx_NEWLINE_xXTargeted prostate biopsy within 6 months prior to dosing, with a clinically significant lesion correlating with an mpMRI visible lesion.Xx_NEWLINE_xXOther clinically significant co-morbidities, such as uncontrolled pulmonary disease, active CNS disease, active infection, or any other condition that might compromise the participant's participation in the study.Xx_NEWLINE_xXMedically significant (symptomatic) bradycardia;Xx_NEWLINE_xXHistory of clinically significant allergic reactions or atopic disease that may pose an increased risk of severe CDX-0158 IRRs.Xx_NEWLINE_xXClinically significant gastritis or peptic ulcer disease that would contraindicate the use of indomethacin.Xx_NEWLINE_xXConcurrent Illness Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) that would compromise the patient's ability to tolerate protocol therapy or would likely interfere with the study procedures or results.Xx_NEWLINE_xXClinically significant active cardiac disease, uncontrolled heart disease and/or history of cardiac dysfunction including any of the followingXx_NEWLINE_xXRisk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia.Xx_NEWLINE_xXPrevious significant urinary obstructive symptomsXx_NEWLINE_xXClinically significant (i.e. active) cardiac disease (e.g. symptomatic coronary artery disease, uncontrolled cardiac arrhythmia, or myocardial infarction within the last 6 months); any history of clinically significant cardiac failureXx_NEWLINE_xXOther clinically significant disease or co-morbidity that may adversely affect the safe delivery of treatment within this trialXx_NEWLINE_xXPresence of clinically significant increased intracranial pressure (e.g. impending herniation) or hemorrhage, uncontrolled seizures, or requirement for immediate palliative treatmentXx_NEWLINE_xXAbnormal ECGs that are clinically significant such as QT prolongation (QTc > 480 msec), clinically significant cardiac enlargement or hypertrophy, new bundle branch block or existing left bundle branch block, or signs of new, active ischemia.Xx_NEWLINE_xXClinically significant pulmonary diseaseXx_NEWLINE_xXClinically significant gastrointestinal abnormalitiesXx_NEWLINE_xXAbnormal and clinical significant coagulation parameters at the discretion of the Investigator, i.e.:Xx_NEWLINE_xXActive or clinically significant cardiac disease including:Xx_NEWLINE_xXAny other unstable or clinically significant concurrent medical conditionXx_NEWLINE_xXClinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalityXx_NEWLINE_xXPatients with significant pulmonary dysfunction, large intracranial metastases, or significant thrombocytopenia (platelet count refractory to transfusion)Xx_NEWLINE_xXSubject with clinically significant woundXx_NEWLINE_xXHave an acute or subacute bowel obstruction or history of chronic diarrhea which is considered clinically significant in the opinion of the investigator.Xx_NEWLINE_xXSignificant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular diseaseXx_NEWLINE_xXUncontrolled or significant cardiac diseaseXx_NEWLINE_xXPatients with significant malabsorption as determined by the treating physicianXx_NEWLINE_xXHistory of clinically significant hemorrhagic or thromboembolic event in the past 6 monthsXx_NEWLINE_xXClinically significant or uncontrolled hypertension or cardiac diseaseXx_NEWLINE_xXKnown clinically significant hypotensionXx_NEWLINE_xXKnown clinically significant autoimmune disorders requiring on-going systemic immune-suppression for controlXx_NEWLINE_xXPatients who have a history of: congestive heart failure, unstable angina, sustained ventricular tachycardia, clinically significant bradycardia, advanced heart block, acute MI less than one year prior to study entry, or clinically significant impairment in cardiovascular function.Xx_NEWLINE_xXHave blood urea nitrogen and serum creatinine (BUN/Cr) without clinically significant abnormalities after review by the study physiciansXx_NEWLINE_xXComplete blood count (CBC) without clinically significant abnormalities after review by the study physiciansXx_NEWLINE_xXHave altered immunity such as autoimmune disorders, clinically significant anemia, hemophilia, and blood dyscrasiasXx_NEWLINE_xXEvidence of significant, uncontrolled concomitant diseaseXx_NEWLINE_xXImpaired cardiac function including any of the following:\r\n* Congenital long QT syndrome or a known family history of long QT syndrome;\r\n* Corrected QT (QTc) > 450 msec;\r\n* History or presence of clinically significant ventricular or atrial tachyarrhythmias;\r\n* Clinically significant resting bradycardia (< 50 beats per minute); \r\n* Myocardial infarction within 1 year of starting study drug;\r\n* Other clinically significant heart disease (e.g., unstable angina, congestive heart failure, or uncontrolled hypertension)Xx_NEWLINE_xXHave clinically significant cardiac diseaseXx_NEWLINE_xXClinically significant psychiatric disease which, in the opinion of the PI or sub-investigator (I), would render immunotherapy and its potential sequelae unsafe or compliance with procedural requirements unlikelyXx_NEWLINE_xXPatients with clinically significant dermatological disorders, e.g., eczema or psoriasis, as judged by the principal investigator, or any unhealed skin wounds or ulcersXx_NEWLINE_xXHistory of clinically significant cardiac or pulmonary dysfunctionXx_NEWLINE_xXPatients with clinically significant peripheral vascular diseaseXx_NEWLINE_xXAnother malignancy that is clinically significant or requires active intervention (chemotherapy or radiation)Xx_NEWLINE_xXMust have significant residual invasive disease at the time of definitive surgery following preoperative chemotherapy. Significant residual disease is defined at least one of the following:Xx_NEWLINE_xXNo clinically significant infections as judged by the treating investigator.Xx_NEWLINE_xXPatients with any clinically significant systemic illness, including serious infection, pulmonary, hepatic, or other organ impairment, that would compromise tolerance and/or timely completion of protocol therapyXx_NEWLINE_xXActive, clinically significant Electrocardiogram (ECG) abnormalitiesXx_NEWLINE_xXEvidence of severe or uncontrolled systemic diseases (example, unstable or uncompensated respiratory, hepatic, renal, cardiac disease, or clinically significant bleeding episodes).Xx_NEWLINE_xXUncontrolled clinically significant pulmonary disease.Xx_NEWLINE_xXClinically significant cardiovascular disease (e.g., uncontrolled or any NYHA Class 3 or 4 CHF, uncontrolled angina, history of MI, unstable angina or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication).Xx_NEWLINE_xXUncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, pulmonary hypertension) that in the opinion of the Investigator would put the patient at significant risk for pulmonary complications during the study.Xx_NEWLINE_xXImpaired cardiac function or clinically significant cardiac diseaseXx_NEWLINE_xXClinically significant, uncontrolled heart disease and/or recent cardiac event within 6 months prior to studyXx_NEWLINE_xXClinically significant signs and/or symptoms of bowel obstruction within 3 months prior to starting treatmentXx_NEWLINE_xXSubject has clinically significant coagulation abnormality unless secondary to AML.Xx_NEWLINE_xXPatients with impaired cardiac function or clinically significant cardiac disease.Xx_NEWLINE_xXImpaired cardiac function or clinically significant cardiac diseases.Xx_NEWLINE_xXSystemic immunosuppressive therapy post HSCT or with clinically significant graft-versus-host disease (GVHD).Xx_NEWLINE_xXCardiac ejection fraction ? 50% and no clinically significant ECG findingsXx_NEWLINE_xXClinically significant cardiac disease or impaired cardiac function, including any of the following:Xx_NEWLINE_xXHistory of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance or drug intakeXx_NEWLINE_xXNo clinically significant cardiac conduction disorder on screening.Xx_NEWLINE_xXSignificant cardiovascular abnormalities as defined by any one of the following:\r\n* Congestive heart failure\r\n* Clinically significant hypotension\r\n* Symptoms of coronary artery disease (angina, dyspnea)\r\n* Presence of cardiac arrhythmias on electrocardiogram (EKG) requiring drug therapyXx_NEWLINE_xXLaboratory parameters for vital functions should be in the normal range or not clinically significant.Xx_NEWLINE_xXHistory of clinically significant hemorrhagic or thromboembolic event in the past 6 monthsXx_NEWLINE_xXSubject has a clinically significant coagulation disorder or disease, defined as a platelet count < 100,000 per microliter or International Normalized Ratio > 1.5 within 4 weeks of surgery;Xx_NEWLINE_xXParticipant has persistent diarrhea or clinically significant malabsorption syndrome or known sub-acute bowel obstruction ? Grade 2, despite medical managementXx_NEWLINE_xXPatients who, in the opinion of the Investigator, have significant medical or psychosocial problems that warrant exclusion. Examples of significant problems include, but are not limited to:Xx_NEWLINE_xXNo evidence of significant cardiac or pulmonary dysfunctionXx_NEWLINE_xXSignificant comorbidity (cirrhosis, severe coronary artery disease, significant psychiatric illness, or other that may compromise the ability to safely administer the therapy at the discretion of the primary investigator)Xx_NEWLINE_xXClinically significant uncontrolled condition(s)Xx_NEWLINE_xXClinically significant persistent immune-related adverse events following prior therapy.Xx_NEWLINE_xXPatients with concurrent severe and/or uncontrolled concurrent medical conditions that could compromise participation in the study (e.g., uncontrolled diabetes mellitus defined by a glucose greater than 1.5 ULN in spite of adequate medical treatment, clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection)Xx_NEWLINE_xXPatients with any clinically significant unrelated systemic illness (e.g., serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the patient’s ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or resultsXx_NEWLINE_xXHistory of osteonecrosis of the hip or have evidence of structural bone abnormalities in the proximal femur on MRI scan that are symptomatic and clinically significant.Xx_NEWLINE_xXClinically active cerebral metastases.Xx_NEWLINE_xXParticipants should not have clinically significant peripheral vascular disease or vascular disease (including aortic aneurysm or aortic dissection)Xx_NEWLINE_xXClinically significant peripheral artery disease (e.g., claudication with < 1 block) or any other arterial thrombotic eventXx_NEWLINE_xXRisk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardiaXx_NEWLINE_xXHave current or prior history of infection or clinically significant adverse events (AEs) associated with an exogenous implant(s) or device(s) that cannot be easily removedXx_NEWLINE_xXClinically significant valvular heart diseaseXx_NEWLINE_xXPatients who have had a previous allogeneic transplant within 6 months and have evidence of clinically significant graft versus host diseaseXx_NEWLINE_xXPresence of clinically significant ascitesXx_NEWLINE_xXDecompensated liver disease as evidenced by clinically significant ascites refractory to diuretic therapy, hepatic encephalopathy, or coagulopathyXx_NEWLINE_xXSignificant co-morbid condition or disease which in the judgment of the investigator would place the patient at undue risk or interfere with the study; examples include, but are not limited to cirrhotic liver disease, sepsis, or recent significant traumatic injuryXx_NEWLINE_xXPatients with clinically significant cardiomyopathy requiring treatmentXx_NEWLINE_xXHistory of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelaeXx_NEWLINE_xXParticipants with poorly controlled diabetes or with evidence of clinically significant diabetic vascular complicationsXx_NEWLINE_xXHistory of clinically significant or uncontrolled cardiac disease.Xx_NEWLINE_xXRecent or ongoing clinically significant GI disorder, e.g. Crohn's Disease, Ulcerative Colitis, or prior total or partial gastrectomy.Xx_NEWLINE_xXKnown history of ischemic cardiac disease (including angina requiring anti-anginal medications, myocardial infarction, coronary artery disease documented on cardiac catheterization or ischemia documented on stress test), congestive heart failure, clinically significant arrhythmia or conduction system abnormalities, clinically significant valvular disease, clinically significant pericardial effusion or EF below the lower limit of normalXx_NEWLINE_xXPatients with clinically significant unexplained bleeding within 28 days prior to entering the studyXx_NEWLINE_xXHistory of clinically significant (as determined by the treating physician) atrial arrhythmiaXx_NEWLINE_xXResearch participant without clinically significant encephalopathy/new focal deficitsXx_NEWLINE_xXConcurrent disease or condition that would interfere with study participation or safety, such as:\r\n* Active, clinically significant infection requiring the use of parenteral anti-microbial agents, or grade > 2 by NCI CTCAE (v 4.03) within 14 days prior to enrollment\r\n* Clinically significant bleeding diathesis or coagulopathy, including known platelet function disorders\r\n* Non-healing wound, ulcer, or bone fracture\r\n* Bone marrow disorder including myelodysplasiaXx_NEWLINE_xXClinically significant abnormality on electrocardiogram (ECG)Xx_NEWLINE_xXSignificant weight loss (> 10%) in the prior 3 monthsXx_NEWLINE_xXPHASE I: Clinically significant malabsorption syndromeXx_NEWLINE_xXPHASE II: Clinically significant malabsorption syndromeXx_NEWLINE_xXActive infection or antibiotics within 48 hours prior to study enrollment, including unexplained fever (temp > 38.1°C), if deemed clinically significant by the treating physician.Xx_NEWLINE_xXPresence of any clinically significant findings at entry for medical history, laboratory values, or physical examinationXx_NEWLINE_xXSignificant vascular diseaseXx_NEWLINE_xXNo arrhythmia interpreted by the study cardiologist to be clinically significantXx_NEWLINE_xXSignificant cardiac impairmentXx_NEWLINE_xXSignificant vascular diseaseXx_NEWLINE_xXMust have significant residual invasive disease at the time of definitive surgery following preoperative chemotherapy. Significant residual disease is defined as at least one of the following:Xx_NEWLINE_xXNo clinically significant infections as judged by the treating physician.Xx_NEWLINE_xXPatients with psychiatric disability judged by the investigator to be clinically significant so as to preclude informed consent or compliance with drug intakeXx_NEWLINE_xXSignificant comorbidity: Patients with clinically significant and uncontrolled major disease or disorder that could exacerbate potential toxicities, confound safety assessments, require excluded therapy for management, or limit study compliance.Xx_NEWLINE_xXClinically significant conditions that increase the risk for antiangiogenic therapy.Xx_NEWLINE_xXTreatment with clinically significant metabolic enzyme inducers within 14 days before the first dose of the study drug; clinically significant metabolic enzyme inducers are not permitted during this studyXx_NEWLINE_xXAny significant tobacco history within the past five yearsXx_NEWLINE_xXOther clinically significant co-morbidities, such as uncontrolled pulmonary disease, active CNS disease, active infectionXx_NEWLINE_xXEvidence of increased intracranial pressure (midline shift > 5 mm, clinically significant papilledema, vomiting and nausea, or reduced level of consciousness)Xx_NEWLINE_xXPatients with a significant other medical conditions that would make them unsuitable for transplantXx_NEWLINE_xXSignificant cardiac disease within 6 monthsXx_NEWLINE_xXHistory of previous clinically significant GI bleed in the last 6 months prior to first doseXx_NEWLINE_xXClinically significant peripheral vascular diseaseXx_NEWLINE_xXNo evidence of significant cardiac or pulmonary dysfunctionXx_NEWLINE_xXHistory of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance or oral drug intakeXx_NEWLINE_xXClinically significant valvular heart disease or uncontrollable high-risk cardiac arrhythmiaXx_NEWLINE_xXAny significant uncontrolled intercurrent systemic illnessXx_NEWLINE_xXActive infection or antibiotics within 48 hours prior to study enrollment, including unexplained fever (temp > 38.1°C) if deemed clinically significant by the treating physician.Xx_NEWLINE_xXClinically significant acute pancreatitis within 12 weeks of treatment with protocol therapy as indicated by the presence of two of the three following criteria: abdominal pain in the epigastrium, often with radiation to the back, serum amylase and/or lipase greater than three times the upper limit of normal, and/or characteristic findings (peripancreatic inflammation, fat necrosis, etc.) from abdominal imaging; clinically significant will be defined as that requiring oral narcotics or hospital admissionXx_NEWLINE_xXClinically significant cardiac disease as defined in the protocolXx_NEWLINE_xXFor patients with history of major coronary artery disease in the judgment of the responsible physician, a cardiac stress test (either exercise or pharmacologic) that demonstrates clinically significant abnormalities when performed within 4 weeks of first dose of study drugXx_NEWLINE_xX>= grade 1 proteinuria at baseline or clinically significant impairment of renal functionXx_NEWLINE_xXSignificant uncontrolled intercurrent illnessXx_NEWLINE_xXClinically significant cardiac diseaseXx_NEWLINE_xXHistory of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelaeXx_NEWLINE_xXOther serious illnesses or medical conditions including but not limited to:\r\n* Unstable cardiac disease despite treatment, myocardial infarction within 6 months prior to study entry\r\n* History of significant neurologic or psychiatric disorders including dementia or seizures\r\n* Active clinically significant uncontrolled infection\r\n* Active peptic ulcer disease defined as unhealed or clinically active\r\n* Hypercalcemia \r\n* Active drug addiction including alcohol, cocaine or intravenous drug use defined as occurring within the 6 months preceding diagnosis\r\n* Chronic obstructive pulmonary disease, defined as being associated with a hospitalization for pneumonia or respiratory decompensating within 12 months of diagnosis; this does not include obstruction from tumor\r\n* Autoimmune disease requiring therapy, prior organ transplant, or human immunodeficiency virus (HIV) infection \r\n* Interstitial lung disease\r\n* Hepatitis C by historyXx_NEWLINE_xXAny >grade 1 persistent clinically significant toxicities from prior chemotherapy.Xx_NEWLINE_xXHistory of or presence of clinically significant ventricular or atrial tachyarrhythmiasXx_NEWLINE_xXClinically significant resting bradycardiaXx_NEWLINE_xXHistory of significant hypotensive episode requiring hospitalizationXx_NEWLINE_xXClinically significant cardiovascular disease or cardiac insufficiency,cardiomyopathy, preexisting clinically significant arrhythmia, acute myocardial infarction within 3 months of enrolment, angina pectoris within 3 months of enrolment.Xx_NEWLINE_xXUnstable coronary disease or clinically significant electrocardiogram (ECG) (12-lead) abnormalities, as determined by the investigatorXx_NEWLINE_xXSubjects who have clinically significant graft versus host disease requiring treatment and /or have >grade 2 persistent non hematological toxicity related to transplantXx_NEWLINE_xXNo history of significant vascular disease (eg aortic aneurysm)Xx_NEWLINE_xXResearch participants with other clinically significant medical disorders that could compromise their ability to tolerate protocol therapy or would interfere with the study procedures or resultsXx_NEWLINE_xXSignificant cardiac diseaseXx_NEWLINE_xXPatients with a history of clinically significant cutaneous drug reaction to minocycline, as documented in the patient medical recordsXx_NEWLINE_xXHistory of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance or oral drug intakeXx_NEWLINE_xXNo significant immunodeficiencyXx_NEWLINE_xXEvidence or history of significant cardiac diseaseXx_NEWLINE_xXHistory of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelaeXx_NEWLINE_xXOther clinically significant ECG abnormalities including 2nd degree (Type II) or 3rd degree atrioventricular (AV) block.Xx_NEWLINE_xXThe patient has LVEF ?40% by ECHO or MUGA scan and no clinically significant abnormalities in 12-lead ECGXx_NEWLINE_xXSubjects with a clinically significant or unstable medical condition that would preclude safe and complete study participationXx_NEWLINE_xXHistory of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelaeXx_NEWLINE_xXHistory of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance or oral drug intakeXx_NEWLINE_xXNo significant hematologic abnormalitiesXx_NEWLINE_xXHearing: a) No clinically significant hearing loss, defined in Section 6.2, number 9.Xx_NEWLINE_xXThe subject has a history of clinically significant hematemesis or a recent history of hemoptysis of > 2.5 mL of red blood or other signs indicative of pulmonary hemorrhage or evidence of endobronchial lesion(s)Xx_NEWLINE_xXHistory of significant cerebrovascular disease in the past 6 months or ongoing event with active symptomsXx_NEWLINE_xXPatients with impaired cardiac function or clinically significant cardiac diseases as defined by the protocolXx_NEWLINE_xXClinically significant resting brachycardia (< 50 beats per minute)Xx_NEWLINE_xXHistory of or presence of clinically significant ventricular or atrial tachyarrhythmiasXx_NEWLINE_xXClinically significant peripheral vascular diseaseXx_NEWLINE_xXAdequate cardiac function defined as no clinically significant history of arrhythmia as determined by the principal investigator (PI) and/or the treating physician, history of myocardial infarction (MI) or clinically significant abnormal electrocardiogram (EKG), as determined by the PI and/or the treating physician, within 3 months prior to study enrollment; cardiac function will be assessed by history and physical examinationXx_NEWLINE_xXHistory of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelaeXx_NEWLINE_xXClinically significant systemic illness with manifestations of significant organ dysfunction which in the judgment principal investigator (PI) or associated investigator (AI) would render the patient unlikely to tolerate the protocol therapy or complete the studyXx_NEWLINE_xXEvidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of resultsXx_NEWLINE_xXClinically significant valvular heart diseaseXx_NEWLINE_xXSignificant co-morbidity indicated by major organ system dysfunctionXx_NEWLINE_xXPresence of clinically relevant ascitisXx_NEWLINE_xXPatients with clinically significant unexplained bleeding within 28 days prior to entering the studyXx_NEWLINE_xXSubject has a clinically significant peripheral artery disease, e.g., those with claudication, within 6 monthsXx_NEWLINE_xXClinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection that requires medical treatment within 4 weeks of dosingXx_NEWLINE_xXHistory of significant cardiac disorders:Xx_NEWLINE_xXClinically significant cardiovascular disease defined as: i. Left ventricular ejection fraction (LVEF) ? 50%, measured within 3 months prior to Day 1 confirmed by ECHO/MUGA ii. Congestive heart failure requiring medical therapy iii. Chronic stable angina requiring medical therapy iv. Prior cerebrovascular accident with sequelae c. Clinically significant pulmonary disease defined as: i. Forced expiratory volume in 1 second (FEV1) ? 65% of expected ii. Lung diffusing capacity for carbon monoxide (DLCO) ? 65% of expected Confirmed by pulmonary tests. d. Diabetes mellitus with symptomatic end-organ damage (e.g., retinopathy, nephropathy, neuropathy, vasculopathy) e. Autoimmune inflammatory conditions (e.g., rheumatoid arthritis, systemic lupus erythematous, inflammatory bowel disease, or similar) requiring chronic disease modifying therapy (e.g., etanercept, adalimumab, infliximab, rituximab, methotrexate, or similar) f. Class III obesity defined as a Body Mass Index (BMI) > 40 kg/m2 g. Renal impairment defined as serum creatinine > 1.3 mg/dL (> 115 µmol/L) or creatinine clearance <70 ml/min h. Clinically significant cognitive impairment defined as requiring medical therapy and/or assistance with activities of daily livingXx_NEWLINE_xXKnown clinically significant liver diseaseXx_NEWLINE_xXConcurrent, clinically significant, active malignancies within two years of study enrollment.Xx_NEWLINE_xXPatients with impaired cardiac function or clinically significant cardiac disease:Xx_NEWLINE_xXResting ECG with clinically significant abnormal findings;Xx_NEWLINE_xXHistory or clinical evidence of any surgical or medical condition which the investigator judges as likely to interfere with the results of the study or pose an additional risk in participating (eg, active or clinically significant history of disease involving a major organ system—vascular, cardiac, pulmonary, hepatic, gastrointestinal, gynecologic, hematologic, neurologic, neoplastic, renal, endocrine or immunodeficiency, autoimmune or clinically significant active psychiatric disorders)Xx_NEWLINE_xXPatients with clinically significant unexplained bleeding within 28 days prior to entering the studyXx_NEWLINE_xXClinically significant cardiac diseaseXx_NEWLINE_xXHistory of significant cerebrovascular disease or event with significant symptomsXx_NEWLINE_xXEvidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of resultsXx_NEWLINE_xXKnown impaired cardiac function or clinically significant cardiac diseaseXx_NEWLINE_xXOther clinically significant co-morbiditiesXx_NEWLINE_xXCentral nervous system disorders or psychiatric disability judged by the investigator to be clinically significant to preclude informed consent or interfere with complying with protocol treatmentsXx_NEWLINE_xXClinically significant peripheral vascular diseaseXx_NEWLINE_xXClinically significant hearing loss or ringing in the earsXx_NEWLINE_xXPatients must have an electrocardiogram (EKG) that shows no significant abnormalities that are suggestive of active cardiac diseaseXx_NEWLINE_xXSignificant cardiac eventsXx_NEWLINE_xXClinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) which in the judgment of the Principal or Associate Investigator would compromise the patient’s ability to tolerate PEG-Intron or are likely to interfere with the study procedures or resultsXx_NEWLINE_xXClinically quantifiable disease burden defined as:Xx_NEWLINE_xXUncontrolled clinically significant arrhythmiasXx_NEWLINE_xXHas clinically significant heart disease that affects normal activitiesXx_NEWLINE_xXSignificant ECG abnormalities.Xx_NEWLINE_xXSignificant screening electrocardiogram (ECG) abnormalities;Xx_NEWLINE_xXAll clinically significant toxicities from prior chemotherapy must be ? Grade 1.Xx_NEWLINE_xXUncontrolled concurrent significant medical or psychological co-morbidityXx_NEWLINE_xXPatients with concurrent severe and/or uncontrolled concurrent medical conditions that could compromise participation in the study (e.g., uncontrolled hypertension and/or diabetes mellitus, clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection)Xx_NEWLINE_xXDONOR: Significant pulmonary diseaseXx_NEWLINE_xXHistory of clinically significant heart problemsXx_NEWLINE_xXPredicted not to have significant clinical progression at 4 monthsXx_NEWLINE_xXClinically significant glaucoma, retinitis pigmentosa, or macular degeneration.Xx_NEWLINE_xXAdequate recovery in the investigators opinion from any clinically significant toxicity from prior therapyXx_NEWLINE_xXClinically significant medical conditions including active or uncontrolled infections, new or recurrent malignancy, serious cardiac, pulmonary, or renal disease, and uncontrolled diabetes.Xx_NEWLINE_xXAny other serious uncontrolled medical disorders or psychological conditions that may interfere with study conduct including but not limited to: clinically significant active infectionXx_NEWLINE_xXClinically significant electrolyte imbalance ? Grade 2.Xx_NEWLINE_xXImplanted pacemaker, defibrillator or deep brain stimulator, or documented clinically significant arrhythmiasXx_NEWLINE_xXEvidence of increased intracranial pressure (midline shift > 5 mm, clinically significant papilledema, vomiting and nausea or reduced level of consciousness)Xx_NEWLINE_xXHistory of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelaeXx_NEWLINE_xXHas any clinically significant co-morbidities.Xx_NEWLINE_xXHistory of clinically significant hemorrhagic or thromboembolic event in the past 6 monthsXx_NEWLINE_xXHistory of clinically significant cardiac diseaseXx_NEWLINE_xXOngoing or clinically significant active infection as judged by the investigator.Xx_NEWLINE_xXOngoing or clinically significant active infection as judged by the investigator.Xx_NEWLINE_xXClinically significant ECG changesXx_NEWLINE_xXPatient with significant cardiac, renal or hematologic or pulmonary dysfunctionXx_NEWLINE_xXSignificant cardiac or peripheral vascular arterial diseaseXx_NEWLINE_xXPrior or ongoing clinically significant illness, medical condition, surgical history, physical finding, electrocardiogram (ECG) finding, or laboratory abnormalityXx_NEWLINE_xXPatients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that would compromise the patient’s ability to tolerate protocol therapy or would likely interfere with the study procedures or resultsXx_NEWLINE_xXPatients with clinically significant severe cardiorespiratory disease.Xx_NEWLINE_xXPatients with clinically significant ophthalmologic findings (as determined by an ophthalmologist) during screening should be excluded from the trialXx_NEWLINE_xXClinically significant systemic illness (e.g. serious active infections or significant vital other organ dysfunction), that in the judgment of the principal investigator (PI) would likely compromise the patient’s ability to tolerate protocol therapy or significantly increase the risk of complicationsXx_NEWLINE_xXSignificant cardiac dysfunction:Xx_NEWLINE_xXSignificant circulatory disorders in the past 6 monthsXx_NEWLINE_xXClinically significant cardiac disease or impaired cardiac functionXx_NEWLINE_xXNo evidence of significant cardiac or pulmonary dysfunctionXx_NEWLINE_xXClinically significant peripheral vascular diseaseXx_NEWLINE_xXHistory of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelaeXx_NEWLINE_xXClinically significant, uncontrolled heart disease and/or recent cardiac events.Xx_NEWLINE_xXRECURRENT/ PROGRESSIVE DIPG (STRATUM 1): Patients have any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the ability of the patient to tolerate protocol therapy or put them at additional risk for toxicity or would interfere with the study procedures or resultsXx_NEWLINE_xXNON-PROGRESSED DIPG (STRATUM 2): Patients have any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the ability of the patient to tolerate protocol therapy or put them at additional risk for toxicity or would interfere with the study procedures or resultsXx_NEWLINE_xXPatients must not have known impaired cardiac function or clinically significant cardiac diseaseXx_NEWLINE_xXHas a medical history of clinically significant lung diseasesXx_NEWLINE_xXClinically significant electrolyte imbalance ? grade 2.Xx_NEWLINE_xXImpaired cardiac function or clinically significant cardiac diseases, including any of the following:Xx_NEWLINE_xXClinically significant cardiac diseaseXx_NEWLINE_xXTumors clinically staged as unresectable diseaseXx_NEWLINE_xXHistory of clinically significant hypercalcemiaXx_NEWLINE_xXImpaired cardiac function or clinically significant cardiac diseases, including any of the following:Xx_NEWLINE_xXAny other concurrent severe and/or uncontrolled concomitant medical condition that could compromise participation in the study (e.g., clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection)Xx_NEWLINE_xXClinically significant ascites or clinical evidence or history of portosystemic hypertension or cirrhosis.Xx_NEWLINE_xXActive and clinically significant systemic or localized infection.Xx_NEWLINE_xXSubject has had clinically-significant hematemesis or hemoptysis of > 0.5 teaspoon of red blood, or other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatmentXx_NEWLINE_xXSignificant organ dysfunction.Xx_NEWLINE_xXWithin normal limit hematopoietic capacity, hepatic and renal function; values outside those limits may be allowed at the digression of the principle investigator (PI), if they are determined as not clinically significantXx_NEWLINE_xXHistory of clinically significant cardiac dysfunctionXx_NEWLINE_xXCurrent diagnosis of any other active or clinically significant non-breast cancerXx_NEWLINE_xXAbnormal 12-lead electrocardiogram (ECG) judged to be clinically significant by the Investigator;Xx_NEWLINE_xXHistory of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance or oral drug intakeXx_NEWLINE_xXClinically significant ascitesXx_NEWLINE_xXOther current, severe, uncontrolled systemic disease (e.g., clinically significant\n             metabolic disease, wound healing disorders, ulcers)Xx_NEWLINE_xXScarring or significant skin disease on both upper arms.Xx_NEWLINE_xXClinically significant cardiac disease, including:Xx_NEWLINE_xXKnown clinically significant liver diseaseXx_NEWLINE_xXClinically significant co-morbiditiesXx_NEWLINE_xXHave clinically significant cardiac diseaseXx_NEWLINE_xXOngoing, significant , uncontrolled medical condition.Xx_NEWLINE_xXNormal electro cardio gram (ECG) or ECG with no clinically significant findings;Xx_NEWLINE_xXSubject with electrocardiogram (ECG) abnormalities on a 12-lead ECG performed within 14 days before start of the study drug that are considered by the Investigator to be clinically significant.Xx_NEWLINE_xXClinically significant bleeding within 28 days of study Day 1Xx_NEWLINE_xXClinically significant hypotensionXx_NEWLINE_xXClinically significant autoimmune disorders requiring on-going systemic immune-suppression for controlXx_NEWLINE_xXAny clinically significant and uncontrolled major medical conditionXx_NEWLINE_xXSubjects with clinically significant ascitesXx_NEWLINE_xXClinically significant cardiac diseaseXx_NEWLINE_xXDisease progression either clinically or radiographically after 1-2 previous regimens.Xx_NEWLINE_xXPatient has a urinalysis obtained (=< 14 days prior to randomization) and the results are deemed not clinically significant by the investigatorXx_NEWLINE_xXAny clinically significant cardiac disease defined as NYHA class III or IV.Xx_NEWLINE_xXECG with no clinically significant findings;Xx_NEWLINE_xXSignificant vascular disease or recent peripheral arterial thrombosisXx_NEWLINE_xXImpaired cardiac function or significant heart disease, including any one of the following:\r\n* Angina pectoris within 3 months\r\n* Acute myocardial infarction within 3 months\r\n* Corrected QT (QTc) > 450 msec on the screening electrocardiogram (ECG)\r\n* A past medical history of clinically significant ECG abnormalities or a family history of prolonged QT-interval syndrome\r\n* Other clinically significant heart disease (e.g. heart failure, uncontrolled/labile hypertension, or history of poor compliance with an antihypertensive regimen)Xx_NEWLINE_xXA history or evidence of current clinically significant uncontrolled arrhythmias;Xx_NEWLINE_xXUncontrolled systemic disease (e.g., clinically significant cardiac, pulmonary or metabolic disease)Xx_NEWLINE_xXClinically significant pulmonary, endocrine, neurologic, hematologic, gastrointestinal (GI), autoimmune, psychiatric or genitourinary disease unrelated to HCC that in the judgment of the investigator should preclude treatment with dalantercept or sorafenib.Xx_NEWLINE_xXClinically significant active pulmonary riskXx_NEWLINE_xXHas clinically significant graft-versus-host disease requiring treatmentXx_NEWLINE_xXEvidence of significant hepatic, hematologic, or immunologic disease.Xx_NEWLINE_xX-  Evidence of any significant disease or condition that could affect compliance with the protocol or interpretation of results.Xx_NEWLINE_xXHistory of significant vascular disease.Xx_NEWLINE_xXHistory of or evidence of clinically significant uncontrolled cardiac arrhythmiasXx_NEWLINE_xXUrinalysis: No clinically significant abnormalitiesXx_NEWLINE_xXHistory of repeated and clinically relevant episodes of syncope or other paroxysmal, ventricular, or other significant arrhythmiasXx_NEWLINE_xXImpaired cardiac function or clinically significant cardiac diseases.Xx_NEWLINE_xXSignificant symptomatic deterioration of lung function.Xx_NEWLINE_xXClinically significant and uncontrolled major medical condition(s) including but not limited to:Xx_NEWLINE_xXSubject exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to:\r\n* Active systemic fungal infection\r\n* Diagnosis of fever and neutropenia within 1 week prior to study drug administrationXx_NEWLINE_xXSignificant pulmonary compromiseXx_NEWLINE_xXImpaired cardiac function or clinically significant cardiac diseases, including any of the following:Xx_NEWLINE_xXClinically significant resting bradycardiaXx_NEWLINE_xXAny other clinically significant heart diseaseXx_NEWLINE_xXPatients with concurrent severe and/or uncontrolled concurrent medical conditions that could compromise participation in the study (i.e. uncontrolled diabetes mellitus, clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection).Xx_NEWLINE_xXClinically significant pulmonary hypertension, as defined by the requirement for ongoing pharmacologic treatment or the consistent or intermittent use of supplemental home oxygen.Xx_NEWLINE_xXClinically significant anemia unrelated to MDSXx_NEWLINE_xXNo evidence of a clinically significant active infectionXx_NEWLINE_xXClinically significant toxicities from prior chemotherapy must be resolved to Grade ?Xx_NEWLINE_xXHistory of clinically significant psychiatric illness that would prevent the patient from providing a valid ICF and complying with protocol requirementsXx_NEWLINE_xXSignificant history of cardiac diseaseXx_NEWLINE_xXSignificant vascular diseaseXx_NEWLINE_xXClinically significant acute or unstable cardiovascular, cerebrovascular (stroke), renal, gastrointestinal, pulmonary, immunological, endocrine, or central nervous system disordersXx_NEWLINE_xXAbnormal ECGs which are clinically significant such as QT prolongation (QTc > 480 msec), clinically significant cardiac enlargement or hypertrophy, new bundle branch block, or signs of active ischemia. Patients with evidence of prior infarction who are New York Heart Association (NYHA) functional classes II, III, or IV are excluded, as are patients with marked arrhythmias such as Wolff Parkinson White pattern or complete atrioventricular (AV) dissociation.Xx_NEWLINE_xXThe patient has uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, pulmonary hypertension) that in the opinion of the Investigator would put the patient at significant risk for pulmonary complications during the study.Xx_NEWLINE_xXHistory of significant cerebrovascular disease in the past 3 months or ongoing event with active symptoms or sequelaeXx_NEWLINE_xXHistory of clinically significant cardiac disease.Xx_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* Clinically-significant hemoptysis of >= 0.5 teaspoon (2.5 ml) of red blood\r\n* Any other signs indicative of pulmonary hemorrhageXx_NEWLINE_xXClinically significant abnormalities of glucose metabolism.Xx_NEWLINE_xXEvidence of clinically significant cardiac abnormalities, uncontrolled hypotension, left ventricular ejection fraction below the lower limit of normal for the site or experience of significant cardiac interventional procedures.Xx_NEWLINE_xXClinically-significant thrombosis within 3 months of screeningXx_NEWLINE_xXParticipants who have not recovered from clinically significant adverse effect(s)/toxicity(s) of the previous therapy.Xx_NEWLINE_xXSecond primary malignancy that is clinically detectable or clinically significant at the time of consideration for study enrollmentXx_NEWLINE_xXHistory of significant cardiac dysfunctionXx_NEWLINE_xXHistory of significant cerebrovascular disease or event with significant symptoms or sequelae.*Xx_NEWLINE_xXPatients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that would compromise the patient’s ability to tolerate protocol therapy or would likely interfere with the study procedures or resultsXx_NEWLINE_xXLifetime history of suicidality, homicidality, or clinically significant hostility/aggressionXx_NEWLINE_xXSignificant vascular disease.Xx_NEWLINE_xXSignificant history of cardiac diseaseXx_NEWLINE_xXClinically significant gastro-intestinal disease, including uncontrolled inflammatory gastro-intestinal diseasesXx_NEWLINE_xXClinically significant cardiac disease;Xx_NEWLINE_xXOther clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system (CNS) disease, active infection, or any other condition that could compromise the subject's participation in the studyXx_NEWLINE_xXClinically significant cardiac disease or impaired cardiac functionXx_NEWLINE_xXPatients with a history of clinically significant venous thromboembolism will be excluded on cohort 2; patients with tumor associated thrombus in the renal vein will not be excludedXx_NEWLINE_xXClinically significant cardiac or pulmonary dysfunctionXx_NEWLINE_xXClinically significant history of liver diseaseXx_NEWLINE_xXHas a significant clinical disease or conditionXx_NEWLINE_xXSignificant renal impairment as determined per investigator discretionXx_NEWLINE_xXSignificant concurrent disease.Xx_NEWLINE_xXImpaired cardiac function or clinically significant cardiac diseases, including any of the following:Xx_NEWLINE_xXClinically significant resting bradycardiaXx_NEWLINE_xXOther clinically significant heart diseaseXx_NEWLINE_xXPatients with concurrent severe and/or uncontrolled concurrent medical conditions that could compromise participation in the study (e.g. uncontrolled hypertension and/or diabetes mellitus, clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection).Xx_NEWLINE_xXHistory of severe cardiac disease or clinically significant arrhythmia (either on ECG or by history) which, in the opinion of the Investigator, will interfere with the safety of the individual subject.Xx_NEWLINE_xXPersistent clinically significant toxicities from prior chemo ? Grd 1Xx_NEWLINE_xXPersistent clinically significant toxicities from prior chemo ? Grd 1Xx_NEWLINE_xXHistory of any clinically significant local or systemic infectious disease within 4 weeks prior to initial treatment administrationXx_NEWLINE_xXHistory of significant neurological or psychiatric disordersXx_NEWLINE_xXNo clinically significant infections as judged by the treating investigator.Xx_NEWLINE_xXA history of clinically significant disease that places subject at an unacceptable risk for study entryXx_NEWLINE_xXSignificant active cardiac disease within the previous 6 months:Xx_NEWLINE_xXClinically significant untreated system illness, such as seriously infections, autoimmunity or organ dysfunction, which in the judgement of the Principal or Associate Investigators would compromise the patient’s ability to tolerate the investigational agents or are likely to interfere with the study procedures or resultsXx_NEWLINE_xXClinically significant unrelated systemic illness, such as serious infections or organ dysfunction, which in the judgement of the Principal or Associate Investigators would compromise the patient’s ability to tolerate the investigational agents or are likely to interfere with the study procedures or resultsXx_NEWLINE_xXClinically significant unrelated systemic illness, such as serious infections or organ dysfunction, which in the judgment of the Principal or Associate Investigators would compromise the patient’s ability to tolerate the investigational agents or are likely to interfere with the study procedures or resultsXx_NEWLINE_xXHistory of clinically significant haemoptysis within the past 3 monthsXx_NEWLINE_xXPatients with clinically significant unexplained bleeding within 28 days prior to entering the studyXx_NEWLINE_xXImpaired cardiac function or clinically significant cardiac diseasesXx_NEWLINE_xXClinically significant encephalopathyXx_NEWLINE_xXHistory or evidence of clinically significant pulmonary disease that precludes the use of general anesthesiaXx_NEWLINE_xXClinically significant obstructive airway diseaseXx_NEWLINE_xXSubjects must be free of any clinically significant disease other than cancer that would interfere with the study evaluationsXx_NEWLINE_xXClinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, or clinically significant cardiac arrhythmiasXx_NEWLINE_xXOther clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise the patient’s participation in the studyXx_NEWLINE_xXAny clinically significant electrolyte imbalance, particularly hypokalemia and hypomagnesemia, should be corrected before treatmentXx_NEWLINE_xXNo specific organ function parameters are required; however, significant abnormalities should be discussed with the study PI (this is especially the case for significant renal dysfunction)Xx_NEWLINE_xXSubjects must be free of any clinically significant disease other than cancer that would interfere with the study evaluationsXx_NEWLINE_xXSerum bilirubin < 2 x ULN, or considered not clinically significant by the study doctor or designeeXx_NEWLINE_xXKnown clinically significant autoimmune disorders requiring systemic immunosuppression for controlXx_NEWLINE_xXHistory of clinically significant cardiac or pulmonary dysfunctionXx_NEWLINE_xXPatient has clinically active diverticular diseaseXx_NEWLINE_xXSignificant psychiatric historyXx_NEWLINE_xXSustained or clinically significant cardiac arrhythmiasXx_NEWLINE_xXPatients with clinically significant illnesses which, according to the Investigator, could compromise participation in the study;Xx_NEWLINE_xXPatient has had no clinically significant change in renal status within 3 months prior to screening, according to Investigator's review of clinical patient records.Xx_NEWLINE_xXUncontrolled clinically significant arrhythmia in last 6 months.Xx_NEWLINE_xXAny clinically significant comorbidities, such as uncontrolled pulmonary disease, known impaired cardiac function or clinically significant cardiac disease (specified below), active CNS disease, active infection, or any other condition that could compromise the participant's participation in the study.Xx_NEWLINE_xXAbnormalities on 12-lead ECG including, but not limited to, changes in rhythm and intervals that, in the opinion of the investigator, are considered to be clinically significant.Xx_NEWLINE_xXClinically significant cardiac diseaseXx_NEWLINE_xXSignificant cognitive impairmentXx_NEWLINE_xXMarried or cohabiting with a significant other of either gender for more than one yearXx_NEWLINE_xXSignificant pain during core biopsy as reported by the patientXx_NEWLINE_xXSignificant kidney disease that would inhibit administration of gabapentinXx_NEWLINE_xXManometry felt to be clinically indicatedXx_NEWLINE_xXSubjects with clinically significant uncontrolled cardiac diseaseXx_NEWLINE_xXReport a clinically significant level of FCR (as assessed with the Fear of Cancer Recurrence Inventory Short Form >= 13)Xx_NEWLINE_xXFree from significant psychiatric historyXx_NEWLINE_xXConcurrent clinically significant infections as determined by the treating investigator.Xx_NEWLINE_xXClinically significant pulmonary compromise (e.g. require supplemental oxygen)Xx_NEWLINE_xXOther uncontrolled significant illness.Xx_NEWLINE_xXClinically significant cardiac or pulmonary diseaseXx_NEWLINE_xXClinically significant uncontrolled condition(s).Xx_NEWLINE_xXClinically significant gastrointestinal disorderXx_NEWLINE_xXPatients with any known significant cardiac abnormality.Xx_NEWLINE_xXAny clinically significant Grade ?3 immune-related adverse event (irAE)Xx_NEWLINE_xXClinically significant comorbid medical conditions or lab abnormalitiesXx_NEWLINE_xXHistory of clinically significant coagulation or platelet disorder in the past 12 monthsXx_NEWLINE_xXIntermediate phase lymphedema; defined clinically as significant persistent pitting edema on physical examXx_NEWLINE_xXHistory of or current clinically significant immunodeficiencyXx_NEWLINE_xXHistory of or current clinically significant alloimmunization to leukocyte antigensXx_NEWLINE_xXImpaired cardiac function or clinically significant heart disease, including any one of the following:\r\n* Angina pectoris within 3 months\r\n* Acute myocardial infarction within 3 months\r\n* Corrected QT (QTc) > 450 msec for males and > 470 msec for females on the screening electrocardiogram (ECG)\r\n* A past medical history of clinically significant ECG abnormalities or a family history of prolonged QT-interval syndrome\r\n* Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor adherence with an antihypertensive regimen)Xx_NEWLINE_xXPatient has acute bleeding that is clinically significant within 24 hours before the start of study treatment.Xx_NEWLINE_xXClinically significant elevation of liver function tests prior to the first day of dosing (FDD) that at the discretion of the treating physician would preclude the administration of an azole antifungalXx_NEWLINE_xXAspartate transaminase (AST), alanine transferase (ALT) within institutional limits of normal or judged to be not clinically significant by the investigatorXx_NEWLINE_xXBlood urea nitrogen (BUN) within institutional limits of normal or judged to be not clinically significant by the investigatorXx_NEWLINE_xXAny significant cardiac, hepatic or renal diseaseXx_NEWLINE_xXSuitable candidate for surgery (meets appropriate performance status, no significant cardiac/renal/hepatic dysfunction)Xx_NEWLINE_xXEvidence or history of clinically significant allergic reactions to vareniclineXx_NEWLINE_xXClinically significant bacteremia or fungemiaXx_NEWLINE_xXAcute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal dysfunction, which in the opinion of the investigator precludes administration of the study vaccineXx_NEWLINE_xXPresence of clinically significant infections or congenital or acquired immunodeficiencyXx_NEWLINE_xXsustained clinically-significant worsening (investigator's assessment) from baseline granulocyte, platelet, or hemoglobin values (? 2 values, separated by ? 2 weeks)Xx_NEWLINE_xXSignificant active cardiac disease within the previous 6 months, including:Xx_NEWLINE_xXImpaired cardiac function or clinically significant cardiac diseasesXx_NEWLINE_xXAny other concurrent severe and/or uncontrolled concomitant medical condition that could compromise participation in the study (e.g., clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection)Xx_NEWLINE_xXImpaired cardiac function or clinically significant cardiac diseasesXx_NEWLINE_xXSubjects with clinically significant increased intracranial pressure or uncontrolled seizures.Xx_NEWLINE_xXSubject has significant auto-immune diseaseXx_NEWLINE_xXSubjects with clinically significant increased intracranial pressure (eg, impending herniation or requirement for immediate palliative treatment) or uncontrolled seizuresXx_NEWLINE_xXOther concurrent clinically active malignant disease, requiring treatmentXx_NEWLINE_xXUnstable or clinically significant concurrent medical conditionXx_NEWLINE_xXSignificant co-morbid condition or disease which in the judgment of the Investigator would place the subject at undue risk or interfere with the study; examples include, but are not limited to, cirrhotic liver disease, sepsis, recent significant traumatic injury, and other conditionsXx_NEWLINE_xXClinically significant edema requiring diuretic therapyXx_NEWLINE_xXEvidence or history of clinically significant allergic reactions to vareniclineXx_NEWLINE_xXComplete blood count (CBC) including diff & platelets - without clinically significant abnormalitiesXx_NEWLINE_xXAcute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.Xx_NEWLINE_xXClinically significant abnormalities on electrocardiogram (ECG) at screening.Xx_NEWLINE_xXBe clinically stableXx_NEWLINE_xXHave BUN/Cr (Blood urea nitrogen and serum creatinine) without clinically significant abnormalities after review by the study physiciansXx_NEWLINE_xXLiver enzymes without clinically significant abnormalities after review by the study physiciansXx_NEWLINE_xXCBC (complete blood count) without clinically significant abnormalities after review by the study physiciansXx_NEWLINE_xXHEALTHY VOLUNTEER: Subject is mentally or legally incapacitated, has significant emotional problems at the time of prestudy (screening) visit or expected during the conduct of the study or has a history of a clinically significant psychiatric disorder within the last 5 years; subjects who have had situational depression may be enrolled in the study at the discretion of the investigatorXx_NEWLINE_xXSignificant valvular disease, or significant pulmonary disease requiring supplemental oxygen therapyXx_NEWLINE_xXHas clinically significant corneal diseaseXx_NEWLINE_xXEvidence of significant uncontrolled concomitant disease that in the opinion of the investigator could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome)Xx_NEWLINE_xXHistory of clinically significant or uncontrolled cardiac disease.Xx_NEWLINE_xXCardiac ejection fraction ? 50%, no evidence of pericardial effusion as determined by an ECHO, and no clinically significant ECG findingsXx_NEWLINE_xXClinically significant cardiac disease within last 12 monthsXx_NEWLINE_xXHistory of clinically significant or active cardiac diseaseXx_NEWLINE_xXActive clinically significant infectionXx_NEWLINE_xXResolution of any clinically significant non-hematological toxicities (if any) from previous treatments to ? Grade 1 by C1D1.Xx_NEWLINE_xXClinically significant gastrointestinal malabsorption syndromeXx_NEWLINE_xXSignificant ophthalmologic abnormality,Xx_NEWLINE_xXImpaired cardiac function or clinically significant cardiac diseaseXx_NEWLINE_xXPatients with clinically significant and unstable renal and/or liver disease (eg, transplant recipients in rejection)Xx_NEWLINE_xXElectrocardiogram (EKG), vitals and laboratory values outside of normal limits at the time of enrollment, unless these are deemed not clinically significant by clinicianXx_NEWLINE_xXClinically severe cardiovascular disease or clinically significant electrocardiogram (ECG) abnormality.Xx_NEWLINE_xXUncontrolled, clinically significant pulmonary disease.Xx_NEWLINE_xXSignificant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of resultsXx_NEWLINE_xXno evidence of active/clinically significant bleeding. May be evidence of punctate hemorrhage w/in tumor as long as not considered clinically significant to warrant urgent surgical evacuationXx_NEWLINE_xXWith significant heart or pulmonary disease.Xx_NEWLINE_xXEvidence of clinically significant immunosuppressionXx_NEWLINE_xXHistory of or presence of clinically significant ventricular or atrial tachyarrhythmiasXx_NEWLINE_xXClinically significant resting bradycardiaXx_NEWLINE_xXpre-existing clinically significant dysfunction of the heart or Chronic Obstructive Pulmonary Disease (COPD)Xx_NEWLINE_xXConcomitant use or administration of clinically significant enzyme inducers less than or equal to (<=) 14 days before the first dose of TAK-580.Xx_NEWLINE_xXClinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 monthsXx_NEWLINE_xXClinically significant abnormalities on electrocardiogram (ECG)Xx_NEWLINE_xXHistory of clinically significant cardiac dysfunctionXx_NEWLINE_xXClinically significant active infectionXx_NEWLINE_xXUncontrolled/significant heart diseaseXx_NEWLINE_xXAny clinically significant comorbidities, such as uncontrolled pulmonary disease, known impaired cardiac function or clinically significant cardiac disease (specified below), active central nervous system disease, active infection, or any other condition that could compromise the participant's participation in the study. Participants with any of the following cardiovascular conditions are excluded:Xx_NEWLINE_xXAbnormalities on 12-lead ECG including, but not limited to, changes in rhythm and intervals that in the opinion of the investigator are considered to be clinically significant.Xx_NEWLINE_xXEvidence of clinically significant immunosuppressionXx_NEWLINE_xXis clinically unstable and/orXx_NEWLINE_xXKnown, clinically important cardiac or respiratory diseaseXx_NEWLINE_xX