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+History or evidence of cardiovascular risk including any of the following:\r\n* LVEF < LLN (lower limit of normal range)\r\n* A QT interval corrected for heart rate using the Bazett’s formula QTcB >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization\r\n* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic >140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Patients with intra-cardiac defibrillators\r\n* Known cardiac metastases
+Medical illness unrelated to HL, which in the opinion of the study physician will preclude administration of chemotherapy safely; this includes patients with uncontrolled infection (including opportunistic), chronic renal failure, myocardial infarction (MI) within the past 6 months, unstable angina, or cardiac arrhythmias other than chronic atrial fibrillation, or second malignancy requiring active treatment
+Patients who have the following risk factors are considered to be at increased risk for cardiac toxicity and must have documented left ventricular ejection fraction (LVEF) by echocardiogram greater than institution’s lower limit of normal (or 55% if threshold for normal not otherwise specified by institutional guidelines) obtained within 3 months\r\n* Prior treatment with anthracyclines\r\n* Prior treatment with trastuzumab\r\n* A New York Heart Association (NYHA) classification of II controlled with treatment\r\n* Prior central thoracic radiation therapy (RT), including RT to the heart.\r\n* History of myocardial infarction within 12 months (patients with history of myocardial infarction within 6 months are excluded)
+History of any of the following within the last 6 months prior to study entry:\r\n* Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures  \r\n* Ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures\r\n* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia) \r\n* Pulmonary embolism\r\n* New York Heart Association (NYHA) class III or IV heart failure \r\n* Placement of a pacemaker for control of rhythm
+Patients must not have a history of or evidence of cardiovascular risks including any of the following:\r\n* QT interval corrected for heart rate using the Bazett’s formula (QTcB) >= 480 msec. at baseline\r\n* History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within the past 24 weeks prior to registration\r\n* History prior to registration or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Left ventricular ejection fraction (LVEF) =< lower limit of normal on cardiac echocardiogram (echo) or multi gated acquisition scan (MUGA)\r\n* Intra-cardiac defibrillator\r\n* History of abnormal cardiac valve morphology (>= grade 2) documented by ECHO (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study\r\n* History or evidence of current clinically significant uncontrolled cardiac arrhythmias; clarification: subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible\r\n* Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy
+Patients with a history of the following within =< 6 months of study entry are NOT eligible:\r\n* Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures\r\n* Ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures\r\n* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)\r\n* New York Heart Association (NYHA) class III or IV heart failure\r\n* Pulmonary embolism
+Adequate cardiac function, defined as:\r\n* No electrocardiogram (EKG) evidence of acute ischemia\r\n* No EKG evidence of active, clinically significant conduction system abnormalities\r\n* No EKG evidence of > grade 2 (> 480 ms) corrected QT (QTc) prolongation \r\n* Prior to study entry, any EKG abnormality at screening not felt to put the patient at risk has to be documented by the investigator as not medically significant\r\n* No uncontrolled angina or severe ventricular arrhythmias\r\n* No clinically significant pericardial disease\r\n* No history of myocardial infarction within 6 months prior to registration\r\n* No class 3 or higher New York Heart Association congestive heart failure
+History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
+A history of any of the following: sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes, cardiac arrest, Mobitz II second degree heart block or third degree heart block; known presence of dilated, hypertrophic, or restrictive cardiomyopathy
+Current or history of congestive heart failure New York Heart Association (NYHA) class 3 or 4, or any history of documented diastolic or systolic dysfunction (left ventricular ejection fraction [LVEF] < 50%, as measured by MUGA scan or echocardiogram); prior to study entry, any electrocardiography (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
+Patient has clinically significant, uncontrolled heart disease and/or recent events including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 12 months prior to treatment start\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Patient has a left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening\r\n* History of any cardiac arrhythmias, eg., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months prior to treatment start\r\n* Family history of corrected QT interval (QTc) prolongation or of unexplainable sudden death at < 50 years of age\r\n* On screening 12 lead electrocardiogram (ECG), any of the following cardiac parameters: bradycardia (heart rate < 50 at rest), tachycardia (heart rate > 90 at rest), PR interval > 220 msec, QRS interval > 109 msec, or Fridericia corrected QT (QTcF) > 450 msec; congenital long QT syndrome or family history of long QT syndrome\r\n* Systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg\r\n* Bradycardia (heart rate < 50 at rest), by ECG or pulse, at screening
+Have documented major electrocardiogram (ECG) abnormalities which are clinically significant at the investigator's discretion (for example, symptomatic or sustained atrial or ventricular arrhythmias, second- or third-degree atrioventricular block, bundle-branch blocks, ventricular hypertrophy, or recent myocardial infarction).
+Active congestive heart failure or ventricular arrhythmia requiring medication
+History or evidence of increased cardiovascular risk including any of the following: \r\n* Left ventricular ejection fraction (LVEF) < institutional lower limit of normal\r\n* A QT interval corrected for heart rate using the Bazett’s formula >= 480 msec\r\n* Current clinically significant uncontrolled arrhythmias\r\n** Exception: subjects with controlled atrial fibrillation for > 30 days prior to randomization are eligible\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization\r\n* Current >= class II congestive heart failure as defined by New York Heart Association\r\n* Patients with intra-cardiac defibrillators\r\n* Abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study
+History of congestive heart failure, arrhythmias, acute coronary syndrome or torsades de pointes
+Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
+Any history of ventricular fibrillation or torsades de pointes
+ELIGIBILITY CRITERIA - PHASE II (ARM D): Patients with NYHA class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia may not be enrolled
+Clinically significant active cardiac disease, uncontrolled heart disease and/or a history of cardiac dysfunction including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 12 months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Patient has a left ventricular ejection fraction (LVEF) < 50% as determined by echocardiogram (ECHO) \r\n* History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening\r\n* Long QT syndrome or known family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: \r\n** Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia\r\n** Concomitant use of medication(s) with a known risk to prolong the QT interval and/or days prior to starting study drug) or replaced by safe alternative medication\r\n* 12-lead electrocardiogram (ECG), any of the following cardiac parameters:\r\n** QTc > 480 msec\r\n* Hypertension defined as: \r\n** Patients 1-12 years of age with blood pressure that is > 95th percentile for age, height and gender at the time of enrollment \r\n*** The normal blood pressure by height, age and gender tables can be accessed in the Generic Forms section of the PBTC members’ webpage\r\n** Patients who are >= 13 years of age with blood pressure > 130/80 mm of Hg at the time of enrollment\r\n* Note: if a blood pressure (BP) reading prior to enrollment does not meet parameters, blood pressure should be rechecked and documented to be within eligibility range prior to patient enrollment
+Myocardial infarction within six months prior to enrollment or has New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities prior to study entry
+Participants with uncontrolled intercurrent illness including, but not limited to:\r\n* Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities, including any of the following:\r\n** History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to screening\r\n** History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n** Documented cardiomyopathy\r\n** Left ventricular ejection fraction (LVEF) =< 50% as determined by multiple-gated acquisition (MUGA) scan or echocardiogram (ECHO) within six months prior to beginning protocol therapy\r\n** Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block)\r\n** Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:\r\n*** Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia\r\n*** Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued (within 5 half-lives or 7 days prior to starting study drug) or replaced by safe alternative medication\r\n** Systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg at screening\r\n** Impairment of gastrointestinal function or who have gastrointestinal disease that may significantly alter the absorption of study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea or malabsorption syndrome)\r\n** Patient with liver disease and Child-Pugh score B or C
+History or family history of Long QT Syndrome or Torsade de Pointes. Myocardial infarction, CABG, coronary or cerebral artery stenting and /or angioplasty, stroke, cardiac surgery, or hospitalization for congestive heart failure within 3 months or greater than Class 2 Angina Pectoris or NYHA Heart Failure Class >2. QTcF > 470 msec, PR > 280 msec, Mobitz II 2nd degree AV Block, 2:1 AV Block, High Grade AV Block, or Complete Heart Block, unless the patient has an implanted pacemaker or implantable cardiac defibrillator (ICD) with backup pacing capabilities.
+Known cardiopulmonary disease defined as having one or more of the following:\r\n* Uncontrolled high blood pressure (i.e. systolic > 180 mmHg or diastolic > 95 mmHg);\r\n* Cardiomyopathy\r\n* Ischemic heart disease; patients with acute coronary syndrome, myocardial infarction, and/or revascularization (e.g. coronary artery bypass graft, stent) within 6 months of first dose of study drug are excluded; patients with a history of ischemic heart disease who have had revascularization greater than 6 months before screening and who are without cardiac symptoms may enroll\r\n* Arrhythmia (e.g. history of polymorphic ventricular fibrillation or torsade de pointes); patients with symptomatic atrial fibrillation (Afib) incompletely controlled medically, or controlled by device (e.g. pacemaker) or by ablation are excluded; however, patients with stable, asymptomatic AFib for a period of at least 6 months, whose Afib is controlled with medication, or who have a history of paroxysmal AFib are permitted to enroll\r\n* Implantable cardioverter defibrillator\r\n* Congestive heart failure (New York Heart Association [NYHA] class III or IV; or class II with a recent decompensation requiring hospitalization or referral to a heart failure clinic within 4 weeks before screening)\r\n* Moderate to severe aortic and/or mitral stenosis or other valvulopathy (ongoing); mild regurgitation is not excluded\r\n* Pulmonary hypertension
+Clinically significant, uncontrolled heart disease and/ or cardiac repolarization abnormalities including any of the following:\r\n* History of unstable angina pectoris, symptomatic pericarditis, myocardial infarction, coronary artery bypass grafting or coronary angioplasty =< 12 months prior to registration\r\n* History of documented congestive heart failure (New York Heart Association functional classification III - IV)\r\n* Documented cardiomyopathy\r\n* Left ventricular ejection fraction (LVEF) < 50% as determined by echocardiogram (ECHO)\r\n* Clinically significant cardiac arrhythmias (e.g ventricular tachycardia) , left bundle branch block, high-grade atrioventricular (AV) block (e.g bifascucular block, Mobitz type II and third degree AV block)\r\n* Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:\r\n** Risk factors for torsades de pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia\r\n** Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause torsades de pointe that cannot be discontinued (within 5 half-lives or =< 7 days prior to registration) or replaced by safe alternative medication\r\n** Inability to determine the QT interval on screening (QTcF, using Fridericia’ s correction)
+History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
+Known history of symptomatic congestive heart failure (New York Heart Association III-IV), symptomatic or poorly controlled cardiac arrhythmia, complete left bundle branch block, bifascicular block, or any clinically significant ST segment and/or T-wave abnormalities, QTcF > 450 msec prior to randomization.
+Atrial fibrillation with a ventricular rate > 100 beats per minute (bpm) on echocardiograph (ECG) at rest
+Myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
+Participants who have clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g. bifascicular block, Mobitz type II) and third-degree AV block\r\n* Documented cardiomyopathy\r\n* Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening\r\n* Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following\r\n** Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia\r\n** Inability to determine the QT interval on screening (QTcF, using Fridericia’s correction)\r\n* Systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg at screening
+Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiographic (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
+History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or cardiac arrhythmias requiring anti-arrhythmic medications, except for atrial fibrillation that is well controlled with anti arrhythmic medication.
+AZD5363 plus olaparib\r\n* Patients with breast, ovarian and endometrial cancers that carry an AKT1 mutation are excluded from the study due to another ongoing study that enrolls these patients; patients with these tumor types but other mutations can be enrolled in the study\r\n* Patients with type I or type II diabetes mellitus; type II diabetes mellitus is allowed if well controlled by dietary measures alone with a glycated hemoglobin (HbgA1c) < 8%; patients found to have a fasting glucose >= 7 mmol/L (126 mg/dL) or HbgA1c > 8% (64 mmol/L) at screening should be assessed for appropriate management according to local policy, of which those in whom dietary measures alone provide good diabetic control (HbgA1c < 8%) will be eligible for inclusion\r\n* Patient must have no evidence of troponin elevation (any common toxicity criteria [CTC] grade)\r\n* Patient must not have > stage II New York Heart Association (NYHA) classification cardiac status; recent history (i.e., within 6 months) of coronary artery disease or arteriosclerotic cardiovascular disease (angina, myocardial infarction [MI])\r\n* Patient must not have resting left ventricular ejection fraction (LVEF) < 55% measured by multi-gated acquisition (MUGA)/echocardiogram (ECHO)\r\n* Patient must not have PR interval greater than 200 msec\r\n* Patient must not have clinically significant PR (PQ) interval prolongation\r\n* Patient must not have resting LVEF < 55% measured by echocardiogram, regional wall abnormality on ECHO, or any clinically significant structural abnormalities on echocardiogram such as left ventricular hypertrophy or diastolic dysfunction or valvular disease\r\n* Patient must not have QTcF > 480 msec or b) family history of long QT Syndrome or\r\nc) evidence of recent myocardial infarction e.g. within 6 months prior to start of study treatment) or risk of having a re-infarction, or d) history of torsade de pointes or e) QTcF < 350 msec (short QT syndrome)\r\n* Patient must not have intermittent second or third degree atrioventricular (AV) block (second degree AV block [Mobitz Type I and II]; third degree AV block [complete heart block]); incomplete, full or intermittent bundle branch block (QRS 110-120ms with normal QRS and T wave morphology is permitted if there is no evidence of left ventricular hypertrophy); Mobitz type 1, Wenckebach while asleep is permitted\r\n* Patient must not have clinically significant abnormalities in T wave or ST-T changes that can be indicative or be suggestive of acute ischemic changes or acute injury pattern\r\n* Use of any known potent negative inotropic drug - calcium channel blockers: verapamil, diltiazem; beta-blockers (pending discussion with cardiac SKG): metoprolol, propranolol, atenolol, bisoprolol, carvedilol, timolol, sotalol, esmolol; anti- arrhythmics (class I): disopyramide, procainamide, mexiletine; (class III): amiodarone\r\n* Patients with uncontrolled hypotension (systolic blood pressure < 90 mmHg and/or diastolic blood pressure < 50 mmHg)\r\n* Patients with potassium or sodium levels outside the normal range for the site\r\n* Patients with proteinuria (3+ on dipstick analysis or > 500 mg/24 hours)
+History of any of the following within the last 6 months prior to study registration:\r\n* Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures\r\n* Ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures\r\n* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)\r\n* Placement of a pacemaker for control of rhythm\r\n* New York Heart Association (NYHA) class III or IV heart failure \r\n* Pulmonary embolism
+Recent (within 6 months) history of second degree (Type II) or third degree atrioventricular (AV) block cardiomyopathy, myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, stenting, or bypass grafting; Class II, III, or IV heart failure, or symptomatic pericarditis.
+Clinically significant, uncontrolled heart disease and/or recent events including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 12 months prior to screening;\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV);\r\n* Documented cardiomyopathy;\r\n* Patient has a left ventricular ejection fraction < 50% as determined by multi-gated acquisition (MUGA) scan or echocardiography\r\n(ECHO) at screening;\r\n* History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrthymias, or conduction abnormality within 12 months of screening;\r\n* Bradycardia (heart rate < 50 at rest), by electrocardiography (ECG) or pulse, at screening;\r\n* Congenital long QT syndrome or family history of long QT syndrome;\r\n* Systolic blood pressure (SBP) > 160 or < 90 mm Hg
+Clinically significant, uncontrolled heart disease and/or recent events including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty or stenting) or symptomatic pericarditis within 12 months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Patient has a left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) obtained during screening\r\n* History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening; patients with rate-controlled atrial fibrillation or flutter are permitted\r\n* Bradycardia (heart rate < 50 bpm at rest), by electrocardiography (ECG) or pulse, at screening\r\n* Congenital long QT syndrome or family history of long QT syndrome\r\n* Any of the following abnormalities on screening 12-lead ECG:\r\n** QTcF (Fridericia’s formula) > 450 msec\r\n** Bradycardia (heart rate < 50 bpm at rest)\r\n** PR interval > 220 msec\r\n** QRS interval > 109 msec\r\n* Documented cardiomyopathy\r\n* Systolic blood pressure > 160 mmHg or < 90 mmHg at screening
+Significant medical comorbidities, including uncontrolled hypertension (diastolic blood pressure greater than 115 mm Hg), unstable angina, congestive heart failure (greater than New York Heart Association class II), severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia, poorly controlled diabetes, severe chronic pulmonary disease, coronary angioplasty, or myocardial infarction within 6 months prior to screening, or uncontrolled atrial or ventricular cardiac arrhythmias.
+A history or evidence of cardiovascular risk including any of the following:\r\n* A QT interval corrected for heart rate using the Bazett's formula (QTc) >= 480 msec\r\n* A history or evidence of current clinically significant uncontrolled arrhythmias\r\n** Exception: subjects with atrial fibrillation controlled for > 30 days prior to study day 1\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to study day 1\r\n* A history or evidence of current >= class I congestive heart failure as defined by the New York Heart Association (NYHA) guidelines\r\n* Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy\r\n* Patients with intra-cardiac defibrillators or permanent pacemakers\r\n* Known cardiac metastases
+Unstable angina or myocardial infarction within 6 months prior cycle 1, day 1, New York Heart Association (NYHA) class III or IV heart failure, left ventricular ejection fraction (LVEF) < 40%, uncontrolled angina, history of severe coronary artery disease, history of torsade de pointes, history of symptomatic pulmonary hypertension, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, corrected QT (QTc) prolongation > 450 msec, or electrocardiographic evidence of acute ischemia or grade 3 conduction system abnormalities unless subject has a pacemaker
+Impaired cardiac function or clinically significant cardiac disease including any of the following:\r\n* Congenital long QT syndrome\r\n* Screening electrocardiogram (ECG) with corrected QT (QTc) interval >= 500 milliseconds\r\n* Myocardial infarction (MI) or unstable angina =< 6 months of course 1, day 1 (C1D1); however, subjects with a history of MI between 6 and 12 months who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event would be eligible\r\n* Symptomatic coronary artery disease (CAD), e.g., angina Canadian class II-IV; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present\r\n* An ECG recorded at screening showing evidence of cardiac ischemia (ST depression of >= 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present\r\n* Other significant ECG abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (defined here as ventricular rate < 50 beats per minute [bpm]); right bundle-branch block + left anterior hemi-block (bifascicular block)\r\n* Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II to IV definitions and/or ejection fraction < 40% by multi gated acquisition scan (MUGA) scan or < 50% by echocardiogram and/or magnetic resonance imaging (MRI) history or presence of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), torsade de pointes, or cardiac arrest\r\n* Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes\r\n* Uncontrolled hypertension, i.e., blood pressure (BP) of >= 160/95; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria\r\n* Any cardiac arrhythmia requiring an anti-arrhythmic medication, excluding stable (i.e., at least 30 days from screening) doses of beta-blockers
+For Part G: Have a baseline electrocardiogram (obtained from Day -14 to Day -1) with any of the following abnormal findings: ventricular arrhythmia, evidence of acute myocardial ischemia, heart block (of any degree), or QTc prolongation (defined as QTcB ?450 milliseconds).
+History or evidence of cardiovascular risk including any of the following:\r\n* A QT interval corrected for heart rate using the Bazett’s formula QTcB >= 480 msec on screening electrocardiography (ECG)\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization\r\n* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study
+Patients with significant cardiovascular disease are excluded, including:\r\n* Myocardial infarction, severe angina, or unstable angina within 6 months prior to administration of first dose of study drug\r\n* History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation)\r\n* Cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication)\r\n* Coronary or peripheral artery bypass graft within 6 months of screening\r\n* History of class III or IV congestive heart failure, as defined by the New York Heart Association
+Significant ventricular arrhythmia (persistent ventricular tachycardia, ventricular fibrillation, resuscitated sudden death)
+Myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
+History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
+The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest
+Persistent or clinically meaningful ventricular arrhythmias.
+History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality in the previous 12 months;
+Significant medical history or unstable medical comorbidities, including:\r\n* Heart disease including congestive heart failure (New York Heart Association [NYHA] grade II or greater); unstable angina; prior myocardial infarction (non-ST elevation myocardial infarction [NSTEMI] or ST elevation myocardial infarction [STEMI]) within 6 months prior to study enrollment; hypertension with a systolic blood pressure of > 150 mm Hg or diastolic blood pressure of > 100 mm Hg while on antihypertensive medication\r\n* Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiogram (ECG), e.g. complete left bundle branch block, third-degree heart block, second-degree heart block, PR interval > 250 msec, mean resting corrected QT value (QTc) of > 470 msec\r\n* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives, or any concomitant medication known to the prolong the QT interval that a patient is unable to stop\r\n* Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease\r\n* Active bleeding diatheses, which in the investigator’s opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol\r\n* Active infection or ongoing antiviral medication for viral infections including hepatitis B, hepatitis C, or human immunodeficiency virus (HIV); screening for chronic conditions is not required; HIV-positive participants on combination antiretroviral therapy are ineligible
+Symptomatic cardiac disease (including symptomatic ventricular dysfunction, symptomatic coronary artery disease, and symptomatic arrhythmias), cerebrovascular event/stroke or myocardial infarction within the past 6 months
+Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality,\r\nincluding any of the following:\r\n* History of myocardial infarction (MI), angina pectoris, symptomatic pericarditis, or coronary artery bypass graft (CABG) within 6 months prior to study entry\r\n* Documented cardiomyopathy\r\n* Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:\r\n** Risk factors for torsades de pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia\r\n** Concomitant medication(s) with a known risk to prolong the QT interval and/or known to cause torsades de pointe that cannot be discontinued or replaced by safe alternative medication (e.g. within 5 half-lives or 7 days prior to starting study drug)\r\n** Inability to determine the QTcF interval\r\n* Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third degree AV block
+Subject had a myocardial infarction within 6 months of enrollment, heart failure (New York Heart Association (NYHA) Class III or IV), uncontrolled angina, severe uncontrolled ventricular arrhythmias, left ventricular ejection fraction (LVEF) ? 40% or evidence of acute ischemia or active conduction system abnormalities.
+Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) Class III or IV heart failure (see Appendix D), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant.
+Any of the following cardiac diseases currently or within the last 6 months as defined by New York Heart Association (NYHA) >= class 2\r\n* Unstable angina pectoris\r\n* Congestive heart failure\r\n* Acute myocardial infarction\r\n* Conduction abnormality not controlled with pacemaker or medication\r\n* Significant ventricular or supraventricular arrhythmias (patients with chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible)\r\n* AZD1775 should not be given to patients who have a history of Torsades de pointes unless all risk factors that contributed to Torsades have been corrected; AZD1775 has not been studied in patients with ventricular arrhythmias or recent myocardial infarction
+History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such as structural heart disease (e.g., severe left ventricular systolic dysfunction, left ventricular hypertrophy), untreated coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), myocardial infarction or atrial thrombotic events within the past 6 months, severe unstable angina, New York Heart Association Class III and IV heart disease or depressed left ventricular ejection fraction (LVEF; previously documented LVEF < 50% without documentation of recovery), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome
+Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation, and ventricular tachycardia)
+Any clinically important abnormalities in rhythm, conduction, or morphology of the resting ECG (e.g., complete left bundle branch block, third-degree heart block, second-degree heart block, PR interval >250msec).
+Uncontrolled or significant cardiovascular disease, including any of the following:\r\n* Corrected QT (QTc) interval > 480 msec (mean value and manually verified) at 3 or more time points within a 24 hour period if necessary\r\n* Diagnosed or expected congenital long QT syndrome\r\n* Concurrent congestive heart failure, prior history of class III/IV cardiac disease (New York Heart Association)\r\n* Left ventricular ejection fraction < 50%\r\n* Prior history of cardiac ischemia or cardiac arrhythmia within the last 6 months; coronary angioplasty or stenting in the previous 12 months\r\n* Any history of second or third degree heart block (may be eligible if the subject currently has a pacemaker)\r\n* Uncontrolled hypertension defined as inability to maintain blood pressure below the limit of 140/90 mmHg\r\n* Known pulmonary hypertension
+Congestive heart failure (New York Heart Association [NYHA] class III to IV), symptomatic cardiac ischemia, unstable angina or myocardial infarction in the previous 6 months prior to first dose, or with a known left ventricular ejection fraction (LVEF) <40%, cardiomyopathy, pericardial disease, clinically relevant cardiac arrhythmia (CTCAE version 4.03 Grade 2 or higher), clinically significant ECG abnormalities, or screening 12-lead ECG showing a baseline prolonged QT interval (baseline QT interval as corrected by Fridericia's formula > 470 msec).
+Cardiac abnormalities:\r\n* Mean QTc interval >= 480 msec at screening\r\n* Acute coronary syndrome (ACS)/acute myocardial infarction (AMI) –within 24 weeks prior to screening\r\n* Percutaneous coronary intervention (PCI)/percutaneous transluminal coronary angioplasty (PTCA) –within 24 weeks prior to screening\r\n* Symptomatic heart failure – New York Heart Association (NYHA) class >= II symptoms
+Clinically important abnormalities in rhythm, conduction, or morphology of resting ECGs, e.g., complete left bundle branch block, third degree heart block
+Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECGs, e.g., complete left bundle branch block, third degree heart block
+Clinically significant cardiac disease or impaired cardiac function, such as:\r\n* Congestive heart failure (CHF) requiring treatment (New York Heart Association [NYHA] grade >= 2) or left ventricular ejection fraction (LVEF) < 50% as determined by multi-gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening\r\n* History or current evidence of clinically significant cardiac arrhythmias, atrial fibrillation and/or conduction abnormality, e.g. congenital long QT syndrome, high-grade/complete atrioventricular (AV)-blockage\r\n* Acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft [CABG], coronary angioplasty, or stenting), < 3 months prior to screening\r\n* QT interval adjusted according to Fredericia (QTcF) > 480 msec on screening electrocardiogram (ECG)
+Hiistory of ventricular arrhythmia
+History or evidence of cardiac risk including any of the following: history or evidence of current clinically significant uncontrolled arrhythmias or arrhythmia requiring treatment with the exceptions of atrial fibrillation and paroxysmal supraventricular tachycardia; history of acute coronary syndromes within 6 months prior to the first dose of study therapy (including myocardial infarction and unstable angina, coronary angioplasty, or stenting); history of uncontrolled hypertension; or any history of congestive heart failure with most recent ejection fraction < 45% (screening left ventricular ejection fraction [LVEF] assessment without history of congestive heart failure CHF is not required)
+Ventricular arrhythmias requiring continuous therapy, or
+Supraventricular arrhythmias including atrial fibrillation, which are uncontrolled.
+New York Heart Association classification III or IV congestive heart failure, known symptomatic coronary artery disease, symptoms of coronary artery disease on systems review, or known cardiac arrhythmias (atrial fibrillation or supraventricular tachycardia [SVT])
+Patients who had had a myocardial infarction within 6 months of enrollment or have New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
+History of any of the following within the last 6 months prior to study entry:\r\n* Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures\r\n* Ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures\r\n* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)\r\n* Placement of a pacemaker for control of rhythm\r\n* New York Heart Association (NYHA) class III or IV heart failure\r\n* Pulmonary embolism
+Documented LVEF of less than or equal to 45% tested in patients with:\r\n* Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or have a history of ischemic heart disease, chest pain\r\n* Age >= 65 years old
+Documented LVEF of less than or equal to 45%, note: testing is required in patients with:\r\n* Age >= 65 years old\r\n* Clinically significant atrial and or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block, or history of ischemic heart disease or chest pain
+Any known cardiac abnormalities such as:\r\n* Congenital long QT syndrome\r\n* Corrected QT (QTc) interval >= 500 milliseconds\r\n* Patients taking drugs leading to significant QT prolongation\r\n* Myocardial infarction within 6 months of cycle1 day 1 (C1D1); (subjects with a history of myocardial infarction between 6 and 12 months prior to C1D1 who are asymptomatic and have had a negative cardiac risk assessment [treadmill stress test, nuclear medicine stress test, or stress echocardiogram] since the event, may participate)\r\n* Other significant electrocardiogram (ECG) abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min)\r\n* Symptomatic coronary artery disease (CAD), e.g., angina Canadian class II-IV; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present\r\n* An ECG recorded at screening showing evidence of cardiac ischemia (ST depression of >= 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present\r\n* Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II to IV definitions and/or ejection fraction < 40% by multi gated acquisition (MUGA) scan or < 50% by echocardiogram and/or magnetic resonance imaging (MRI)\r\n* A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest \r\n* Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes\r\n* Uncontrolled hypertension, i.e., blood pressure (BP) of >= 160/95; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria or\r\n* Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)
+Cardiac abnormalities as evidenced by any of the following: History or current clinically significant uncontrolled arrhythmias or hypertension; Clinically significant conduction abnormalities or arrhythmias, subjects with Bundle Branch Block; Presence of cardiac pacemaker; History or evidence of current >=Class II congestive heart failure as defined by New York Heart Association (NYHA); History of acute coronary syndromes (including unstable angina and myocardial infarction), coronary angioplasty, or stenting within the past 3 months.
+Other significant electrocardiogram (ECG) abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min)
+A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD)
+Severe, active co-morbidity, defined as follows:\r\n* Cardiac symptoms; any of the following should be considered for exclusion:\r\n** Uncontrolled angina, congestive heart failure or myocardial infarction (MI) within (6 months)\r\n** Diagnosed congenital long QT syndrome\r\n** Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)\r\n** Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (> 450 msec)
+Active cardiac arrhythmias with rapid ventricular response (defined as heart rate greater than 100 beats/minute)
+Documented left ventricular ejection fraction (LVEF) of less than or equal to 45% tested in patients with:\r\n* Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block, chest pain, or ischemic heart disease\r\n* Age >= 65 years old
+Uncontrolled angina, congestive heart failure, myocardial infarction (MI) (within last 6 months), congenital long QT syndrome, history of clinically significant ventricular arrhythmia, prolonged QTcF interval on pre-entry electrocardiogram (EKG) (greater than normal range)
+Documented LVEF of less than or equal to 45% tested in patients with:\r\n* Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or have a history of ischemic heart disease, chest pain\r\n* Age >= 65 years old
+No history of arrhythmia (multifocal premature ventricular contractions [PVCs], bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (Common Terminology Criteria for Adverse Events [CTCAE] grade 3) or asymptomatic sustained ventricular tachycardia; atrial fibrillation, controlled on medication is permitted
+Documented left ventricular ejection fraction (LVEF) =< 45% tested in patients:\r\n* Age >= 65 years\r\n* With clinically significant atrial and/or ventricular arrhythmias, including but not limited to: atrial fibrillation, ventricular tachycardia, second- or third-degree heart block, or have a history of ischemic heart disease and/or chest pain.
+Clinically significant, uncontrolled heart disease and/or recent events including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting\r\n* Coronary angioplasty, or stenting) or symptomatic pericarditis within 12 months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Patient has a left ventricular ejection fraction < 40% as determined by multigated acquisition (MUGA) scan or echocardiography (ECHO) (MUGA and ECHO are not required prior to enrollment)
+Since IL-2 is administered following cell infusion:\r\n* Patients will be excluded if they have a history of clinically significant electrocardiogram (ECG) abnormalities, symptoms of cardiac ischemia with evidence of ischemia on a cardiac stress test (stress thallium, stress multigated acquisition [MUGA], dobutamine echocardiogram or other stress test)\r\n* Similarly, patients with a baseline left ventricular ejection fraction (LVEF) < 45 percent (%) will be excluded\r\n* Patients with ECG results of any conduction delays (PR interval > 200 ms, corrected QT [QTC] > 480 ms), sinus bradycardia (resting heart rate < 50 beats per minute), sinus tachycardia (heart rate > 120 beats per minute) will be evaluated by a cardiologist prior to starting the trial; patients with any arrhythmias, including atrial fibrillation/atrial flutter, excessive ectopy (defined as > 20 premature ventricular contractions [PVCs] per minute), ventricular tachycardia or 3rd degree heart block will be excluded from the study unless cleared by a cardiologist\r\n* Patients with pulmonary function test abnormalities as evidenced by a forced expiratory volume in 1 (FEV1) / forced vital capacity (FVC) < 70% of predicted for normality will be excluded
+Patients with the following cardiovascular abnormalities:\r\n* Corrected QT interval (QTc) > 500 msec within 7 days prior to registration for protocol therapy; NOTE: if QTc is > 450 and ? 500 msec, subject to local cardiology review and approval, the patient may be enrolled if the QTc elevation is deemed clinically insignificant\r\n* Acute cardiovascular events within 6 months prior to C1D1: stroke (transient ischemic attack permitted), acute coronary syndrome, peripheral arterial obstruction, clinically significant arrhythmias (e.g., such as paroxysmal atrial fibrillation/atrial flutter, sick sinus syndrome, second or third degree atrio-ventricular blockade); a cardiology consultation may be obtained to clarify clinical significance\r\n* Clinical cardiac heart failure of New York Heart Association class III or IV or left ventricular ejection fraction (LVEF) < 50% as assessed by echocardiogram at screening
+Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any ECG abnormality at screening has to be documented by the Investigator as not medically relevant
+Significant medical history or unstable medical comorbidities, including but not limited to:\r\n* Heart disease including congestive heart failure (New York Heart Association [NYHA] grade II or greater); unstable angina; prior myocardial infarction (non-ST-elevation myocardial infarction [NSTEMI] or ST-elevation myocardial infarction [STEMI]) within 6 months prior to study enrollment; hypertension with a systolic blood pressure of > 150 mm Hg or diastolic blood pressure of > 100 mm Hg while on antihypertensive medication\r\n* Any clinically significant abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second degree heart block\r\n* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval\r\n* Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease\r\n* Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses\r\n* Active infection or ongoing antiviral medication for viral infections including hepatitis B, hepatitis C, or human immunodeficiency virus (HIV). Screening for chronic conditions is not required. HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with osimertinib\r\n* Ongoing use of warfarin (injectable low-molecular weight heparins are permitted). Patients must be off warfarin for > 7 days prior to enrollment
+Patients who have experienced untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction (unstable angina, congestive heart failure, myocardial infarction within the previous 3 months; coronary angioplasty, or stenting or bypass grafting within the past 6 months; cardiac ventricular arrhythmias requiring medication; any history of second (2nd) or third (3rd) degree atrioventricular conduction defects)
+Participants must not have had uncontrolled or significant cardiovascular disease including, but not limited to, any of the following: \r\n* Myocardial infarction or stroke/transient ischemic attack within the past 6 months\r\n* Uncontrolled angina within the past 3 months\r\n* Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes)\r\n* History of other clinically significant heart disease (eg, cardiomyopathy, congestive heart failure with New York Heart Association functional classification III to IV, pericarditis, significant pericardial effusion, or myocarditis)\r\n* Cardiovascular disease-related requirement for daily supplemental oxygen therapy
+History of any of the following within the last 6 months before administration of the first dose of the drug: a) Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures b) Ischemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures c) Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia) d) Placement of a pacemaker for control of rhythm e) New York Heart Association (NYHA) class III or IV heart failure f) Pulmonary embolism.
+Significant cardiovascular disease, including:\r\n* Cardiac failure New York Heart Association (NYHA) class III or IV\r\n* Myocardial infarction, severe or unstable angina within 6 months prior to study day 1\r\n* History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation)\r\n* Cardiac arrhythmia requiring anti-arrhythmic medication(s); note that beta-blockers, calcium channel blockers, and digoxin administered for the purpose rate control of supraventricular tachycardia, including atrial fibrillation and atrial flutter, are not classified as anti-arrhythmic medications for purposes of trial eligibility
+Any clinically important abnormalities in rhythm, conduction or morphology of a resting ECG, e.g., complete left bundle branch block, third degree heart block, that in the opinion of the Investigator render the patient unsuitable for participation in the study
+Significant screening ECG abnormalities, including unstable cardiac arrhythmia requiring medication, atrial fibrillation/flutter, left bundle branch block, 2nd-degree atrioventricular (AV) block type II, 3rd degree AV block, Grade ?2 bradycardia, or corrected QT (QTc) >450 msec (for men) or >470 msec (for women).
+Documented LVEF =< 45% tested in patients with:\r\n* Age >= 65 years\r\n* With clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second- or third-degree heart block or have a history of ischemic heart disease and/or chest pain
+COHORT 1: HORMONE RECEPTOR POSITIVE BREAST CANCER: Known history of cardiac arrhythmias including uncontrolled atrial fibrillation, tachyarrhythmias or bradycardia, history of congestive heart failure, or myocardial infarction or stroke in the previous 3 months will be excluded
+COHORT 2: TRIPLE NEGATIVE BREAST CANCER: Known history of cardiac arrhythmias including uncontrolled atrial fibrillation, tachyarrhythmias or bradycardia, history of congestive heart failure, or myocardial infarction or stroke in the previous 3 months will be excluded
+COHORT 3: ENDOMETRIAL CANCER: Known history of cardiac arrhythmias including uncontrolled atrial fibrillation, tachyarrhythmias or bradycardia, history of congestive heart failure, or myocardial infarction or stroke in the previous 3 months will be excluded
+Cardiac exclusions specific to glasdegib and OX40 containing arms: Any one of the following ongoing or in the previous 6 months: congenital long QT syndrome, torsades de pointes, sustained ventricular tachyarrhythmia, right or left bundle branch block and bifascicular block, unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident (CVA), transient ischemic attack or symptomatic pulmonary emboli, as well as bradycardia defined as < 50 beats per minute (bpm)s. Active cardiac dysrhythmias of NCI CTCAE grade >= 2 (eg, atrial fibrillation) or corrected QT (QTc) interval > 470 msec.
+Known cardiopulmonary disease defined as:\r\n* Unstable angina pectoris\r\n* Congestive heart failure (New York Heart Association [NYHA] class III or IV)\r\n* Myocardial infarction within 6 months prior to first dose (patients who had ischemic heart disease such as acute coronary syndrome (ACS), myocardial infarction (MI), and/or revascularization more than 6 months prior to enrollment and who are without cardiac symptoms may enroll)\r\n* Cardiomyopathy\r\n* Clinically significant cardiac arrhythmia\r\n** History of polymorphic ventricular fibrillation or Torsade de Pointes\r\n** Permanent atrial fibrillation (a fib), defined as continuous a fib for ? 6 months\r\n** Persistent a fib, defined as sustained a fib lasting > 7 days and/or requiring cardioversion in the 4 weeks before screening\r\n** Grade 3 a fib defined as symptomatic and incompletely controlled medically, or controlled with device (e.g. pacemaker) or ablation\r\n** Patients with Paroxysmal a fib or < grade 3 a fib for a period of at least 6 months are permitted to enroll provided that their rate is controlled on a stable regimen\r\n* Implantable cardioverter defibrillator\r\n* Moderate to severe aortic and/or mitral stenosis or other valvulopathy (ongoing)\r\n* Pulmonary hypertension
+Patients must have documented left ventricular ejection fraction (LVEF) by echocardiogram greater than institution’s lower limit of normal (or 55% if threshold for normal not otherwise specified by institutional guidelines) obtained within 3 months prior to registration if they have any of the following risk factors for cardiac toxicities:\r\n* A New York Heart Association (NYHA) classification of II controlled with treatment \r\n* Prior central thoracic radiation therapy (RT), including RT to the heart\r\n* History of myocardial infarction within 12 months prior to registration\r\n* Prior treatment with anthracyclines\r\n* Prior treatment with trastuzumab\r\n* Prior history of other significant impaired cardiac function
+History or presence of an abnormal electrocardiogram (ECG) that is clinically significant in the investigator's opinion, including complete left bundle branch block, second- or third degree heart block, or evidence of prior myocardial infarction Exclusions Related to Infections
+Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening will be documented by the investigator as not medically relevant.
+Patients with uncontrolled or significant cardiovascular disease including, but not limited to, any of the following are ineligible:\r\n* Myocardial infarction or stroke/transient ischemic attack (TIA) within the 6 months prior to consent\r\n* Uncontrolled angina within the 3 months prior to consent\r\n* Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes)\r\n* History of other clinically significant cardiovascular disease (i.e., cardiomyopathy, congestive heart failure with New York Heart Association [NYHA] functional classification III-IV, myocarditis and pericarditis, significant pericardial effusion, significant coronary stent occlusion, deep venous thrombosis, etc.)\r\n* Cardiovascular disease-related requirement for daily supplemental oxygen
+Clinically significant cardiovascular disease including: \r\n* Myocardial infarction within 6 months \r\n* Uncontrolled angina within 6 months\r\n* Congestive heart failure New York Heart Association (NYHA) class 3 or 4 in the past, or history of anthracycline or anthracenedione (mitoxantrone) treatment, unless a screening echocardiogram or multi-gated acquisition scan (MUGA) performed within three months results in a left ventricular ejection fraction that is >= 45%\r\n* History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes)\r\n* Prolonged corrected QT interval by the Fridericia correction formula (QTcF) on the screening electrocardiogram (ECG) > 470 msec\r\n* History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place\r\n* Hypotension (systolic blood pressure < 86 millimeters of mercury or bradycardia with a heart rate of < 50 beats per minute on any ECG taken at the screening visit\r\n* Bradycardia with a heat rate of < 50 beats per minutes in the screening ECG, unless pharmaceutically induced and reversible\r\n* Uncontrolled hypertension as indicated by a resting systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg at the screening visit
+Unacceptable cardiac risk factors defined by any of the following criteria: patients with congenital long QT syndrome, any history of ventricular fibrillation or torsade de pointes, bradycardia defined as heart rate (HR) < 50 beats per minute (bpm), left ventricular ejection fraction < 30%
+Known cardiopulmonary disease defined as one of the following:\r\n* Uncontrolled high blood pressure (ie, systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg)\r\n* Cardiomyopathy or history of ischemic heart disease\r\n* Arrhythmia (eg, history of polymorphic ventricular fibrillation or torsade de pointes); however, patients with < grade 3 atrial fibrillation (a fib) for a period of at least 6 months may enroll; grade 3 a fib is symptomatic and\r\nincompletely controlled medically, or controlled with device (e.g., pacemaker), or ablation; patients with paroxysmal a fib are permitted to enroll\r\n* Implantable cardioverter defibrillator\r\n* Congestive heart failure (New York Heart Association [NYHA] class III or IV; or class II with a recent decompensation requiring hospitalization or referral to a heart failure clinic within 4 weeks before screening), myocardial infarction and/or revascularization (eg, coronary artery bypass graft, stent) within 6 months of first dose of study drug\r\n* Patients who had ischemic heart disease who have had acute coronary syndrome (ACS), myocardial infarction (MI), and/or revascularization greater than 6 months before screening and who are without cardiac symptoms may enroll\r\n* Moderate to severe aortic and/or mitral stenosis or other valvulopathy (ongoing)\r\n* Pulmonary hypertension
+Significant uncontrolled cardiac arrhythmias, including ventricular arrhythmias, congenital long QT syndrome, symptomatic atrial fibrillation, symptomatic bradycardia, right bundle branch block plus left anterior hemiblock or bifasicular block
+Known history of cardiac arrhythmias including atrial fibrillation, tachyarrhythmias or bradycardia, unless arrhythmia is controlled and after cardiology has cleared patient to receive ONC 201; receiving therapeutic agents known to prolong QT interval will be excluded; history of congestive heart failure (CHF), or myocardial infarction (MI) or stroke in the last 3 months will be excluded
+Electrocardiogram (ECG) abnormalities:\r\n* Prolonged corrected QT (QTc) (Bazette’s or Fredericia’s correction) interval on screening ECG (>= 450 msec)\r\n* QRS ? 120 msec\r\n* PR ? 210 msec\r\n* Any prior history, or current evidence of second- or third-degree heart block\r\n* Heart rate ? 40 beats per minute at screening\r\n* ECG second degree heart block (Mobitz’s type 2 or Wenckebach)\r\n* Complete heart block\r\n* Left bundle branch block or bifascicular block (right bundle branch block and left anterior hemiblock together)\r\n* Episodes of ventricular tachycardia
+Patients with clinically significant, uncontrolled cardiovascular disease, such as:\r\n* Unstable angina within 6 months prior to screening\r\n* Myocardial infarction within 6 months prior to screening\r\n* Patients with a history of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Peripheral vascular disease\r\n* Patients with uncontrolled hypertension defined as a systolic blood pressure (SBP) >= 160 mm Hg and/or diastolic blood pressure (DBP) >= 100 mm Hg, with or without anti-hypertensive medication; initiation or adjustment of antihypertensive medication(s) is allowed prior to screening\r\n* Ventricular arrhythmias\r\n* Supraventricular and nodal arrhythmias not controlled with medication\r\n* Other cardiac arrhythmia not controlled with medication\r\n* Patients with corrected QT (QTc) >= 450 ms (male patients) or >= 460 ms (female patients) using Fridericia correction (QTcF) on the screening electrocardiogram (ECG)\r\n* Patients with history of congenital long QT syndrome or history of torsade de pointes
+Subjects with a history of significant cardiac disease including: congestive heart failure requiring therapy; history of myocardial infarction (MI), angina pectoris, coronary artery bypass graft (CABG) within 6 months prior to starting study treatment; clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third degree AV block); left ventricular ejection fraction (LVEF) < 50% evaluated by echocardiogram (ECHO) or multigated acquisition scan (MUGA); increased Fridericia's correction formula (QTcF) (> 450 for men and > 470 for women).
+Clinically significant cardiovascular disease including: 1) myocardial infarction within 6 months of screening visit; 2) uncontrolled angina within 3 months of screening visit; 3) congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subjects with history of congestive heart failure NYHA class 3 or 4 in the past, or history of anthracycline or anthracenedione (mitoxantrone) treatment, unless a screening echocardiogram or multi-gated acquisition scan (MUGA) performed within three months of the Screening visit results in a left ventricular ejection fraction that is >= 50%. 4) history of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsade de pointes). 5) prolonged corrected QT interval by the Fridericia correction formula (QTcF) on the screening electrocardiogram (ECG) > 470 msec. 6) history of Mobitz II second degree or third degree heart block without a permanent pacemaker in place. 7) hypotension (systolic blood pressure < 86 mmHg or bradycardia with a heart rate of < 50 beats per minute on the screening ECG., unless pharmaceutically induced and thus reversible (i.e. beta blockers).
+History of myocardial infarction =< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
+History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
+Has a history of significant cardiac disease, including:\r\n* History of a recent myocardial infarction (within one year), a past myocardial infarction (more than one year ago) along with current coronary symptoms requiring medications and/or evidence of depressed left ventricular function (LVEF < 45% by multigated acquisition [MUGA] or echocardiogram [ECHO])\r\n* Current history of angina/coronary symptoms requiring medications and/or evidence of depressed left ventricular function (LVEF < 45% by MUGA or ECHO)\r\n* Clinical evidence of congestive heart failure requiring medical management (irrespective of ECHO results)
+Clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to: any history of myocardial infarction (MI), stroke, or revascularization; unstable angina or transient ischemic attack prior to enrollment; congestive heart failure prior to enrollment, or left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards prior to enrollment; diagnosed or suspected congenital long QT syndrome; any history of clinically significant atrial or ventricular arrhythmias (such as artrial fibrillation, ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes) as determined by the treating physician; prolonged QTc interval on pre-entry electrocardiogram (> 470 msec) unless corrected after electrolyte replacement.
+Significant, uncontrolled cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation, or ventricular tachycardia).
+Clinically significant uncontrolled heart disease and/or recent cardiac event within 6 months prior to enrollment, such as:\r\n* History of angina pectoris, symptomatic pericarditis, or myocardial infarction\r\n* Left ventricular ejection fraction (LVEF) < 45% as determined by echocardiogram (ECHO) or multi gated acquisition (MUGA) scan\r\n* History or presence of any cardiac arrhythmias, e.g. ventricular, supraventricular, nodal arrhythmias or conduction abnormality; stable atrial fibrillation within 6 months prior to randomization is permitted\r\n* Presence of unstable atrial fibrillation (ventricular response rate > 100 beats per minute [bpm]); NOTE: patients with stable atrial fibrillation\r\n* Resting heart rate < 50 bpm\r\n* Complete left bundle branch block (LBBB), bifascicular block\r\n* Congenital long QT syndrome\r\n* Any clinically significant ST segment and/or T-wave abnormalities\r\n* Corrected QT (QTcF) > 450 msec for males and females using Fridericia’s correction on screening electrocardiogram (ECG) by mean value of triplicate ECGs\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Uncontrolled hypertension defined by a systolic blood pressure (SBP) >= 150 mmHg and/or diastolic blood pressure (DBP) >= 100 mmHg with or without antihypertensive medication; NOTE: initiation or adjustment of antihypertensive medication(s) is allowed prior to screening\r\n* Other clinically significant heart disease or vascular disease
+Has any clinically important abnormalities in rhythm, conduction or morphology of resting ECG, eg, complete left bundle branch block, third-degree heart block, second-degree heart block, or PR interval > 250 milliseconds (ms).
+Medically documented cardiac syncope, uncompensated New York Heart Association (NYHA) class 3 or 4 congestive heart failure, myocardial infarction within the previous 6 months, unstable angina pectoris, uncontrolled hypertension (defined as an average systolic blood pressure [SBP] over 140 or a diastolic blood pressure [DBP] over 90 despite antihypertensive agents), clinically significant repetitive ventricular arrhythmias despite antiarrhythmic treatment, or severe orthostatic hypotension or clinically important autonomic disease; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant; NOTE: there is no lower limit of left ventricular ejection fraction below which patients are excluded from participation
+Since IL-2 is administered following cell infusion:\r\n* Patients will be excluded if they have a history of clinically significant electrocardiogram (ECG) abnormalities, symptoms of cardiac ischemia with evidence of ischemia on a cardiac stress test (stress thallium, stress multigated acquisition [MUGA], dobutamine echocardiogram or other stress test)\r\n* Similarly, patients with a baseline left ventricular ejection fraction (LVEF) < 45% will be excluded.\r\n* Patients with ECG results of any conduction delays (PR interval > 200 ms, corrected QT [QTC] > 480 ms), sinus bradycardia (resting heart rate < 50 beats per minute), sinus tachycardia (heart rate >120 beats per minute) will be evaluated by a cardiologist prior to starting the trial; patients with any arrhythmias, including atrial fibrillation/atrial flutter, excessive ectopy (defined as > 20 premature ventricular contractions [PVCs] per minute), ventricular tachycardia or 3rd degree heart block will be excluded from the study unless cleared by a cardiologist\r\n* Patients with pulmonary function test abnormalities as evidenced by a (forced expiratory volume 1 [FEV1]/forced vital capacity [FVC ] < 70% of predicted for normality will be excluded
+Uncontrolled intercurrent illness including, but not limited to:\r\n* Malabsorption syndrome significantly affecting gastrointestinal function\r\n* Ongoing or active infection requiring parenteral antibiotics\r\n* Impairment of lung function (chronic obstructive pulmonary disease [COPD] > grade 2, lung conditions requiring oxygen therapy)\r\n* Symptomatic congestive heart failure (class III or IV of the New York Heart Association classification for heart disease)\r\n* Unstable angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months\r\n* Clinically significant cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia that is symptomatic or requires treatment [National Cancer Institute -Common Terminology Criteria for Adverse Events, version 4.03, grade 3])\r\n* Fridericia's correction formula (QTcF) >= 480 msec on screening electrocardiography (EKG)\r\n* Known history of clinically significant QT/corrected QT (QTc) prolongation or torsades de pointes (TdP)\r\n* ST depression or elevation of >= 1.5 mm in 2 or more leads\r\n* Diarrhea of any cause >= Common Terminology Criteria for Adverse Events (CTCAE) grade 2\r\n* Psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements including maintenance of a compliance/pill diary\r\n* Symptomatic brain metastases (patients with a history of brain metastases must be clinically stable for more than 4 weeks from completion of radiation treatment and be off steroids)\r\n* Known history of chronic liver or chronic renal failure\r\n* Poor wound healing capacity
+History or evidence of cardiovascular risk including any of the following:\r\n* LVEF< LLN\r\n* A QT interval corrected for heart rate using the Bazett’s formula (QTcB) >= 480 msec;\r\n* History or evidence of current clinically significant uncontrolled arrhythmias\r\n* Clarification: Subjects with atrial fibrillation controlled (defined as not requiring change in cardiac drug dosing, emergency room visit, or hospital admission) for > 30 days prior to dosing are eligible\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to study enrollment\r\n* History or evidence of current >= class II congestive heart failure as defined by New York Heart Association (NYHA)\r\n* Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by antihypertensive therapy;\r\n* Patients with intra-cardiac defibrillators
+Any of the following cardiac abnormalities or history: a) clinically significant abnormal 12-lead electrocardiogram (ECG), QT interval (QT corrected by Bazett's formula [QTCB]) > 480 ms, b) inability to measure QT interval on ECG, c) personal or family history of long QT syndrome, d) implantable pacemaker or implantable cardioverter defibrillator, e) resting bradycardia < 55 beats/min, f) history or evidence of current clinically significant uncontrolled arrhythmias. Exception: subjects with controlled atrial fibrillation for > 30 days prior to randomization are eligible, g) history of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting, within 6 months prior to randomization, h) history or evidence of current >= class II congestive heart failure as defined by New York Heart Association (NYHA), i) treatment refractory hypertension defined as a blood pressure of systolic > 140 mm Hg and/or diastolic > 90 mm Hg which cannot be controlled by antihypertensive therapy, j) cardiac metastases
+Unstable angina or myocardial infarction within 4 months prior to registration, New York Heart Association (NYHA) class II, III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or grade 3 conduction system abnormalities unless subject has a pacemaker
+Left ventricular ejection fraction (LVEF) >= 40% by echocardiography, multigated acquisition (MUGA), or cardiac magnetic resonance imaging (MRI); no uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities (within 28 days of study registration)
+History of myocardial infarction =< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
+Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%; testing is required in patients with:\r\n* Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or have a history of ischemic heart disease or chest pain\r\n* Age >= 65 years’ old
+History or presence of sustained bradycardia (?55 BPM), left bundle branch block, cardiac pacemaker or ventricular arrhythmia. Note: Patients with a supraventricular arrhythmia requiring medical treatment, but with a normal ventricular rate are eligible;
+Myocardial infarction within ONE months prior to enrollment or has New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant.
+Cardiac conditions as follows: uncontrolled hypertension (blood pressure [BP] >= 150/95 mmHg despite medical therapy); acute coronary syndrome within 6 months prior to starting treatment; uncontrolled angina - Canadian Cardiovascular Society grade II-IV despite medical therapy; symptomatic heart failure New York Heart Association (NYHA) class II-IV, prior or current cardiomyopathy, or severe valvular heart disease; prior or current cardiomyopathy including but not limited to the following: known hypertrophic cardiomyopathy or known arrhythmogenic right ventricular cardiomyopathy; previous moderate or severe impairment of left ventricular systolic function (left ventricular ejection fraction [LVEF] < 45% on echocardiography or equivalent on multigated acquisition [MUGA]) even if full recovery has occurred; severe valvular heart disease; baseline LVEF below the lower limit of normal (LLN) measured by echocardiogram (ECHO) or institution’s LLN for MUGA; atrial fibrillation with a ventricular rate > 100 bpm on electrocardiogram (ECG) at rest; corrected QT interval by Fridericia (QTcF) > 470 ms on two or more timepoints or other factors that increase the risk of QT prolongation such as family history of long QT syndrome
+Any of the following cardiac abnormalities (only for patients receiving romidepsin):\r\n* Congenital long QT syndrome;\r\n* Corrected QT (QTc) interval ? 501 milliseconds;\r\n* Patients taking drugs leading to significant QT prolongation;\r\n* Myocardial infarction within 6 months of cycle 1, day 1; (Subjects with a history of myocardial infarction between 6 and 12 months prior to cycle 1, day 1, who are asymptomatic and have had a negative cardiac risk assessment [treadmill stress test, nuclear medicine stress test, or stress echocardiogram] since the event, may participate);\r\n* Other significant electrocardiogram (ECG) abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min);\r\n* Symptomatic coronary artery disease (CAD), e.g., angina Canadian class II-IV; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;\r\n* An ECG recorded at screening showing evidence of cardiac ischemia (ST depression of ? 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;\r\n* Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II to IV definitions and/or ejection fraction < 40% by multitargeted acquisition (MUGA) scan or < 50% by echocardiogram and/or magnetic resonance imaging (MRI);\r\n* A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), torsade de pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD);\r\n* Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes;\r\n* Uncontrolled hypertension, i.e., blood pressure (BP) of ? 160/95; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria; or\r\n* Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)
+Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congestive heart failure (New York Heart Association [NYHA] class >= 3 or left ventricular ejection fraction < 45%), unstable angina pectoris, myocardial infarction within the last 3 months, clinically significant cardiac arrhythmia (i.e., ventricular tachycardia on anti-arrhythmia are excluded; 1st degree atrioventricular [AV] block or asymptomatic left anterior fascicular block [LAFB]/right bundle branch block [RBBB] permissible), or psychiatric illness/social situations that would limit compliance with study requirements
+Clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to: Any history of myocardial infarction (MI), stroke, or revascularization; Unstable angina or transient ischemic attack prior to enrollment; Congestive heart failure prior to enrollment, or left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards prior to enrollment; Diagnosed or suspected congenital long QT syndrome; Any history of clinically significant atrial or ventricular arrhythmias (such as atrial fibrillation, ventricular tachycardia, ventricular fibrillation, or Torsades de pointes) as determined by the treating physician; Prolonged QTc interval on pre-entry electrocardiogram (> 470 msec) unless corrected after electrolyte replacement. Any history of venous thromboembolism including deep venous thrombosis or pulmonary embolism; Uncontrolled hypertension (diastolic blood pressure > 90 mmHg; systolic > 140 mmHg). Patients with hypertension should be under treatment on study entry to effect blood pressure control.
+History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
+History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
+New York Heart Association classification III or IV, known symptomatic coronary artery disease, or symptoms of coronary artery disease on systems review, or uncontrolled current cardiac arrhythmias (atrial fibrillation or supraventricular tachycardia [SVT])
+Patients with the following cardiac conditions are excluded:\r\n* Uncontrolled hypertension (adults: blood pressure [BP] of >= 150/95 despite medical support/management; participants 18 years of age and younger should have a blood pressure =< 95th percentile for age, height and gender; preexisting hypertension in adults should be controlled [either with pharmacological or non-pharmacological methods] at the time of enrollment)\r\n* Acute coronary syndrome within 6 months prior to starting treatment\r\n* Uncontrolled angina – Canadian Cardiovascular Society grade II-IV despite medical support/management\r\n* Heart failure New York Heart Association (NYHA) class II or above\r\n* Prior or current cardiomyopathy including but not limited to the following:\r\n** Known hypertrophic cardiomyopathy\r\n* Known arrhythmogenic right ventricular cardiomyopathy\r\n* Baseline left ventricular ejection fraction (LVEF) =< 55%\r\n* Previous moderate or severe impairment of left ventricular systolic function (LVEF < 50% on echocardiography or equivalent on Multi-Gated Acquisition Scan [MUGA]) even if full recovery has occurred\r\n* Severe valvular heart disease\r\n* Atrial fibrillation with a ventricular rate > 100 beats per minute (bpm) on electrocardiogram (ECG) at rest\r\n* QT interval corrected according to Fridericia’s formula (QTcF) interval > 450 msec or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) are excluded.; the use of medication(s) that can prolong QTc interval is prohibited while treated on this study
+Unstable cardiovascular function:\r\n* Symptomatic ischemia, or\r\n* Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on anti-arrhythmics are excluded; recent onset atrial fibrillation not in sinus rhythm and without cardiology evaluation are excluded; 1st degree AV block or asymptomatic left anterior fascicular block (LAFB)/right bundle branch block (RBBB) are not excluded), or\r\n* Congestive heart failure (chf) of New York Heart Association (NYHA) class >= 3, or\r\n* myocardial infarction (mi) within 3 months
+Any one of the following currently or in the previous 6 months:\r\n* Myocardial infarction\r\n* Congenital long QT syndrome\r\n* Torsade’s de points\r\n* Arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), and left anterior hemiblock (bifascicular block)\r\n* Unstable angina, coronary/peripheral artery bypass graft\r\n* Symptomatic congestive heart failure (congestive heart failure [CHF] New York Heart Association class III or IV)\r\n* Cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism or other clinical significant episode of thrombo-embolic disease (Cases must be discussed in detail with study chair to judge eligibility; anticoagulation (heparin only, no vitamin-K antagonists or factor Xa inhibitors) will be allowed if indicated)\r\n* Ongoing cardiac dysrhythmias of NCI CTCAE grade >= 2, atrial fibrillation of any grade, or QT correction using Fridericia's correction formula (QTcF) interval > 470 msec at screening (except in case of right bundle branch block, these cases must be discussed with sponsor’s medical monitor)
+Participant had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class II, III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities, or treatment refractory hypertension defined as a blood pressure of systolic > 140mmHg and/ or diastolic > 90 mmHg which cannot be controlled by anti–hypertensive therapy; prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
+A history or evidence of cardiovascular risk including any of the following:\r\n* A QT interval corrected for heart rate using the Bazett’s formula (QTcB) >= 480 msec;\r\n* A history or evidence of current clinically significant uncontrolled arrhythmias; clarification: subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible\r\n* A history of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within 6 months prior to alternate assignment\r\n* A history or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) guidelines;\r\n* Patients with intra-cardiac defibrillators;\r\n* Abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study\r\n* Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy
+Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block).
+Patient has clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months), such as:\r\n* Unstable angina within 6 months prior to screening?\r\n* Myocardial infarction within 6 months prior to screening?\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV);\r\n* Uncontrolled hypertension defined by a systolic blood pressure (SBP) >= 160 mm Hg and/or diastolic blood pressure (DBP) >= 100 mm Hg, with or without antihypertensive medication.\r\n* Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening?\r\n* Ventricular arrhythmias\r\n* Supraventricular and nodal arrhythmias not controlled with medication?\r\n* Other cardiac arrhythmia not controlled with medication?\r\n* Corrected QT (QTcF) > 470 ms using Fridericia’s correction on the screening electrocardiography (ECG)
+History or evidence of cardiovascular risk including any of the following:\r\n* Left ventricular ejection fraction (LVEF) < LLN\r\n* A QT interval corrected for heart rate using the Bazett's formula QTcB >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to -enrollment are eligible)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization\r\n* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic > 150 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Known cardiac metastases
+Uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiography (EKG) suggestive of acute ischemia or active conduction system abnormalities
+Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities, including any of the following:\r\n* New York Heart Association functional classification III-IV\r\n* Documented cardiomyopathy\r\n* Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening\r\n* Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block)\r\n* Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesaemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia; concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued (within 5 half-lives or 7 days prior to starting study drug) or replaced by safe alternative medication\r\n* Inability to determine the QT interval on screening (QTcFusing Fridericia’s correction)\r\n* Systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg at screening
+No clinically significant cardiovascular disease including:\r\n* Myocardial infarction (MI) within 6 months\r\n* Uncontrolled angina within 3 months\r\n* Chronic heart failure (CHF) with New York Heart Association (NYHA) class 3 or 4, or patients with NYHA class 3 or 4 in the past, unless a screening echo or multigated acquisition scan (MUGA) performed within three months demonstrates an ejection fraction (EF) > 45% \r\n* History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, Torsades de pointes)\r\n* History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place\r\n* Hypotension (systolic blood pressure [BP] < 86 mmHg) or bradycardia (< 50 beat per minute [bpm]) at screening\r\n* Uncontrolled hypertension (systolic BP >170 mmHg or diastolic BP >105 mmHg at screening)
+Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block)
+Left ventricular ejection fraction (LVEF) >= 40%, no uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities, within 14 days of study registration (within 30 days for pulmonary and cardiac assessments)
+Class II or greater New York Heart Association Functional Classification criteria or serious cardiac arrhythmias likely to increase the risk of cardiac complications of cytokine therapy (e.g. ventricular tachycardia, frequent ventricular ectopy, or supraventricular tachyarrhythmia requiring chronic therapy)
+History or presence of an abnormal electrocardiogram (ECG) that is clinically significant in the investigator's opinion, including complete left bundle branch block, second- or third-degree heart block, or evidence of prior myocardial infarction
+Myocardial infarction (MI) within 6 months prior to study entry, New York Heart Association (NYHA) class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities
+Cardiac: Uncontrolled clinically significant arrhythmias; clinical evidence of significant congestive heart failure (CHF) (NYHA Class III or IV); left ventricular ejection fraction (LVEF) < 50% by echocardiogram
+Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation, or ventricular tachycardia).
+Patients who have the following risk factors are considered to be at increased risk for cardiac toxicities, and must have documented left ventricular ejection fraction (LVEF) by echocardiogram greater than institution’s lower limit of normal (or 55% if threshold for normal not otherwise specified by institutional guidelines) obtained within 3 months\r\n* Prior treatment with anthracyclines\r\n* Prior treatment with trastuzumab\r\n* A New York Heart Association (NYHA) classification of II controlled with treatment\r\n* Prior central thoracic radiation therapy (RT), including RT to the heart\r\n* History of myocardial infarction within 12 months (patients with history of myocardial infarction within 6 months are excluded from the study)
+History of any of the following within the last 6 months prior to study entry: ischemic myocardial event, including angina requiring therapy and artery revascularization procedures; ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures; requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia); placement of a pacemaker for control of rhythm; New York Heart Association (NYHA) class III or IV heart failure; pulmonary embolism
+New York Heart Association classification III or IV, known symptomatic coronary artery disease, or symptoms of coronary artery disease on systems review, or known cardiac arrhythmias (atrial fibrillation or supraventricular tachycardia [SVT])
+Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
+Must not have had any unstable angina or myocardial infarction within 4 months prior to enrollment to treatment, New York Heart Association Class (NYHA) class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or grade 3 conduction system abnormalities unless subject has a pacemaker
+Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant
+Known cardiopulmonary disease defined as one of the following:\r\n* Unstable angina\r\n* Uncontrolled high blood pressure (ie, systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg)\r\n* Cardiomyopathy or history of ischemic heart disease\r\n* Arrhythmia (eg, history of polymorphic ventricular fibrillation or torsade de pointes); permanent atrial fibrillation (a fib) defined as a fib >= 6 months; persistent a fib defined as sustained a fib lasting > 7 days and/or requiring cardioversion in the 4 weeks before screening; however, patients with < grade 3 atrial fibrillation (a fib) for a period of at least 6 months may enroll; grade 3 a fib is symptomatic and incompletely controlled medically, or controlled with device (e.g., pacemaker), or ablation; patients with paroxysmal a fib are permitted to enroll\r\n* Implantable cardioverter defibrillator\r\n* Congestive heart failure (New York Heart Association [NYHA] class III or IV; or class II with a recent decompensation requiring hospitalization or referral to a heart failure clinic within 4 weeks before screening),\r\n* Myocardial infarction and/or revascularization (eg, coronary artery bypass graft, stent) within 6 months of first dose of study drug\r\n* Patients who had ischemic heart disease who have had ACS, MI, and/or revascularization greater than 6 months before screening and who are without cardiac symptoms may enroll\r\n* Moderate to severe aortic and/or mitral stenosis or other valvulopathy (ongoing)\r\n* Pulmonary hypertension
+History of any of the following within the last 6 months before administration of the first dose of the drug:\r\n* Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures\r\n* Ischemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures\r\n* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)\r\n* Placement of a pacemaker for control of rhythm\r\n* New York Heart Association (NYHA) class III or IV heart failure\r\n* Pulmonary embolism
+Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities, including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening\r\n* Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block)\r\n* Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:\r\n* Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia\r\n* Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued (within 5 half-lives or 7 days prior to starting study drug) or replaced by safe alternative medication\r\n* Inability to determine the QT interval on screening (QTcF, using Fridericia’s correction)\r\n* Systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg at screening
+Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:\r\n* Myocardial infarction within the past 6 months \r\n* Uncontrolled angina within the past 6 months \r\n* Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation or Torsades de pointes); controlled atrial fibrillation by itself is not an exclusion criterion
+Any clinically important abnormalities (as assessed by the Investigator) in rhythm, conduction, or morphology of resting Electrocardiograms, e.g., complete left bundle branch block, third degree heart block
+Significant screening ECG abnormalities, including unstable cardiac arrhythmia requiring medication, atrial fibrillation/flutter, left bundle-branch block, 2nd-degree atrioventricular (AV) block type II, 3rd degree AV block, Grade ?2 bradycardia, or QT corrected for heart rate (QTc) >450 msec (for men) or >470 msec (for women).
+Cardiac abnormalities as evidenced by any of the following: clinically significant uncontrolled arrhythmias or uncontrolled hypertension; history or evidence of current >=Class II congestive heart failure as defined by New York Heart Association (NYHA); history of acute coronary syndromes (including unstable angina and myocardial infarction), coronary angioplasty, or stenting within the past 3 months; baseline Corrected QT (QTc) interval using Fridericia's formula >450 milliseconds (msec) or >480 msec in subjects with Bundle Branch Block. QTc value based on single or average of triplicate ECGs obtained over a brief recording period
+History of myocardial infarction =< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
+Unstable angina or myocardial infarction within 4 months of initiating therapy on trial, New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or grade 3 conduction system abnormalities unless subject has a pacemaker
+Cardiac conditions as follows:\r\n* Uncontrolled hypertension (blood pressure [BP] >= 170/100 despite optimal therapy)\r\n* Heart failure New York Heart Association (NYHA) class II or above\r\n* If NYHA class I heart failure, left ventricular ejection fraction (LVEF) by multi-gated acquisition scan (MUGA) or echocardiogram (ECHO) is less than 50%\r\n* Unstable ischemic heart disease (myocardial infarction within 6 months prior to starting treatment, or angina requiring use of nitrates more than once weekly)\r\n* Mean resting corrected QT (QTc) interval using the Fridericia formula (QTcF) > 450 msec/male and > 470 msec/female (as calculated per institutional standards) obtained from 3 electrocardiograms (ECGs) 2-5 minutes apart at study entry, or congenital long QT syndrome\r\n* Patients with significant ventricular or supraventricular arrhythmias and patients with cardiac conduction abnormalities that are not controlled (e.g. with a pacemaker or medication)
+Unstable cardiovascular function:\r\n* Symptomatic ischemia, or\r\n* Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on antiarrhythmic agents are excluded; 1st degree atrioventricular [AV] block or asymptomatic left anterior fascicular block/right bundle branch block [LAFB/RBBB] will not be excluded), or \r\n* Congestive heart failure (CHF) New York Heart Association (NYHA) class >= 3, or \r\n* Myocardial infarction (MI) within 6 months\r\n* Left ventricular ejection fraction < 40 %\r\n* Hypertension > 160 mm Hg systolic or > 100 mm Hg diastolic with or without antihypertensive therapy
+Any life-threatening illness, severe and/or uncontrolled medical condition, or organ system dysfunction, laboratory abnormality, psychiatric illness or other condition which, in the Investigator’s opinion, could compromise the subject’s safety, interfere with the absorption or metabolism of ibrutinib capsules, put the study outcomes at undue risk or affect their participation in the study such as\r\n* Symptomatic, or history of documented congestive heart failure New York Heart Association (NYHA) functional classification III-IV (NYHA) \r\n* Corrected QT interval using Fridericia's formula (QTcF) > 470 msec (unless related to pacemaker) on echocardiogram (EKG) within 21 days of initiation of treatment\r\n* Angina not well-controlled by medication\r\n* Poorly controlled or clinically significant atherosclerotic vascular disease including cerebrovascular accident (CVA), transient ischemic attack (TIA), angioplasty, cardiac or vascular stenting within 6 months prior to enrollment
+Significant cardiac abnormalities such as:\r\n* Myocardial infarction within 3 months of course 1 day 1 (C1D1); (subjects with a history of myocardial infarction between 3 and 12 months prior to C1D1 who are asymptomatic and have had a negative cardiac risk assessment [treadmill stress test, nuclear medicine stress test, or stress echocardiogram] since the event, may participate);\r\n* An electrocardiogram (ECG) recorded at screening showing evidence of cardiac ischemia (ST depression of >= 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not coronary artery disease (CAD) is present;\r\n* Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class III to IV definitions and/or ejection fraction < 30% by multigated acquisition scan (MUGA) scan or < 50% by echocardiogram and/or magnetic resonance imaging (MRI)
+A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), torsade de pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter-defibrillator (AICD)
+No history of myocardial infarction =< 6 months prior to pre-registration or New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
+Documented left ventricular ejection fraction (LVEF) of less than or equal to 45% tested; the following patients will undergo cardiac evaluations:\r\n* Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or\r\n* Age >= 60 years old
+Known cardiac disorder, including:\r\n* Uncontrolled hypertension (blood pressure [BP] of >= 150/95 despite medical support/management)\r\n* Acute coronary syndrome within 6 months prior to starting treatment\r\n* Uncontrolled angina – Canadian Cardiovascular Society grade II-IV despite medical support/management\r\n* Heart failure New York Heart Association (NYHA) class II or above\r\n* Prior or current cardiomyopathy including but not limited to the following:\r\n** Known hypertrophic cardiomyopathy\r\n* Known arrhythmogenic right ventricular cardiomyopathy\r\n* Baseline left ventricular ejection fraction (LVEF) =< 55%\r\n* Previous moderate or severe impairment of left ventricular systolic function (LVEF < 45% on echocardiography or equivalent on multi-gated acquisition scan [MUGA])\r\neven if full recovery has occurred\r\n* Severe valvular heart disease\r\n* Atrial fibrillation with a ventricular rate > 100 beats per minute (bpm) on electrocardiography (ECG) at rest\r\n* Fridericia's correction formula (QTcF) interval > 450 msec or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) are excluded; the use of medication(s) that can prolong corrected QT (QTc) interval is prohibited while treated on this study
+Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%; testing is required in patients with:\r\n* Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or have a history of ischemic heart disease, or chest pain\r\n* Age >= 65 years old\r\n* Prior treatment with significant exposure to anthracyclines or cyclophosphamide
+Unstable ventricular tachycardia or fibrillation
+Significant cardiovascular disease, including:\r\n* Symptomatic left ventricular dysfunction or baseline left ventricular ejection fraction (LVEF) by multigated acquisition scan (MUGA) or echocardiogram (ECHO) of =< lower limit of institutional normal (LVEF < 50%)\r\n* Patients with marked baseline prolongation of QT/QTc interval (QTc interval > 450 msec for males or > 470 msec for females)\r\n* Uncontrolled hypertension: systolic blood pressure of > 140 mmHg or diastolic blood pressure of > 90 mmHg documented on 2 consecutive measurements taken at least 24 hours apart\r\n* Myocardial infarction, severe angina, or unstable angina within 6 months prior to administration of first dose of study drug\r\n* History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation)\r\n* Cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication)\r\n* Coronary or peripheral artery bypass graft within 6 months of screening\r\n* History of class III or IV congestive heart failure as defined by the New York Heart Association
+Any of the following cardiac abnormalities: 1. History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within the past 6 months prior to first dose of study drug. 2. Presence of a cardiac pacemaker, 3. Baseline Corrected QT (Fridericia's formula) interval (QTcF) >=450 millisecond (msec), 4. Uncontrolled arrhythmias. Subjects with rate-controlled atrial fibrillation for >1 month prior to first dose of study drugs may be eligible.
+Uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiogram (EKG) suggestive of acute ischemia or active conduction system abnormalities
+Patients who currently have or have a history of the following within 6 months preceding study entry are not eligible: unstable angina (UA), myocardial infarction (MI), transient ischemic attack (TIA), stroke, deep vein thrombosis (DVT), acute peripheral or pulmonary arterial thromboembolism (PE); clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or torsades de pointes); New York Heart Association class III or IV heart failure
+Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
+Any history of clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation or torsade de pointes)
+Significant cardiovascular disease, including:\r\n* Cardiac failure New York Heart Association (NYHA) class III or IV\r\n* Myocardial infarction, severe or unstable angina within 6 months prior to study day 1\r\n* History of serious arrhythmia (i.e., ventricular tachycardia, or ventricular fibrillation)\r\n* Ventricular cardiac arrhythmias requiring anti-arrhythmic medications\r\n* Known left ventricular ejection fraction (LVEF) =< 50%
+Since IL-2 is administered following cell infusion:\r\n* Patients will be excluded if they have a history of clinically significant electrocardiogram (ECG) abnormalities, symptoms of cardiac ischemia or arrhythmias and have a left ventricular ejection fraction (LVEF) < 45% on a cardiac stress test (stress thallium, stress multi gated acquisition scan [MUGA], dobutamine echocardiogram, or other stress test)\r\n* Similarly, patients who are >= 50 years old with a baseline LVEF < 45% will be excluded\r\n* Patients with ECG results of any conduction delays (PR interval > 200 ms, corrected QT interval [QTC] > 480 ms), sinus bradycardia (resting heart rate < 50 beats per minute), sinus tachycardia (heart rate > 120 beats per minute) will be evaluated by a cardiologist prior to starting the trial; patients with any arrhythmias, including atrial fibrillation/atrial flutter, excessive ectopy (defined as > 20 premature ventricular contractions [PVCs] per minute), ventricular tachycardia, third (3rd) degree heart block will be excluded from the study unless cleared by a cardiologist\r\n* Patients with pulmonary function test abnormalities as evidenced by a forced expiration volume in one second (FEV1)/forced vital capacity (FVC) < 70% of predicted for normality will be excluded
+Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%; testing is required in patients with:\r\n* Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block\r\n* Age >= 60 years old
+Unstable angina or myocardial infarction within 4 months prior to start of treatment, New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or grade 3 conduction system abnormalities unless subject has a pacemaker
+Myocardial infarction or unstable angina within 6 months prior to enrollment or has New York Hospital Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
+Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
+Clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months), such as:\r\n* Unstable angina\r\n* Myocardial infarction\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Uncontrolled hypertension defined by a systolic blood pressure (SBP) >= 160 mm Hg and/or diastolic blood pressure (DBP) >= 100 mm Hg, with or without antihypertensive medication\r\n* Ventricular arrhythmias, or supraventricular/nodal arrhythmias not controlled with medications; other cardiac arrhythmias not controlled with medications\r\n* Left ventricular ejection fraction < 20% corrected QT (QTcF) > 470 ms using Fridericia’s correction on the screening electrocardiogram (ECG)\r\n* Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening
+History of any of the following within the last 6 months prior to study entry: ischemic myocardial event, including angina requiring therapy and artery revascularization procedures; ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures; requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia); placement of a pacemaker for control of rhythm; New York Heart Association (NYHA) class III or IV heart failure; pulmonary embolism
+History of any of the following within the last 6 months prior to study entry: requirement of inotropic support; serious uncontrolled cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia); placement of a pacemaker for control of rhythm
+Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:\r\n* History or presence of sustained ventricular tachyarrhythmia; (patients with a history of atrial arrhythmia are eligible but should be discussed with Novartis prior to enrollment)\r\n* Any history of ventricular fibrillation or torsade de pointes\r\n* Bradycardia defined as heart rate (HR) < 50 beats per minute (bpm); patients with pacemakers are eligible if HR >= 50 bpm\r\n* Screening electrocardiogram (ECG) with a corrected QT (QTc) > 470 msec\r\n* Right bundle branch block + left anterior hemiblock (bifascicular block)\r\n* Patients with myocardial infarction or unstable angina =< 12 months prior to starting study drug\r\n* Other clinically significant heart disease (e.g., congestive heart failure [CHF] New York [NY] Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
+History of any of the following within the last 6 months before administration of the\r\nfirst dose of the drug:\r\n* Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures\r\n* Ischemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures\r\n* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)\r\n* Placement of a pacemaker for control of rhythm\r\n* New York Heart Association (NYHA) class III or IV heart failure\r\n* Pulmonary embolism
+Active or severe hepatic, cardiovascular, or cerebrovascular disease, including myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
+History or presence of clinically significant ventricular arrhythmias, atrial fibrillation, resting bradycardia, or conduction abnormality
+Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes), New York Heart Association (NYHA) class III-IV heart disease or cardiac ejection fraction measurement of < 40% at baseline
+Patient has a clinically significant cardiac disease or impaired cardiac function, such as: \r\n* The presence of cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association class III/IV congestive heart failure, or uncontrolled hypertension \r\n* Documented major electrocardiogram (ECG) abnormalities (not responding to medical treatments) \r\n* Major abnormalities documented by echocardiography (ECHO) with Doppler (for example, moderate or severe heart valve function defect and/or left ventricular [LV] ejection fraction < 50%, evaluation based on the institutional lower limit of normal) \r\n* Predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress (for example, family history of aneurysms, Marfan-Syndrome, bicuspid aortic valve, evidence of damage to the large vessels of the heart documented by computed tomography [CT] scan/magnetic resonance imaging [MRI] with contrast)
+History or presence of clinically significant ventricular arrhythmias, atrial fibrillation, resting bradycardia, or conduction abnormality
+Ejection fraction (EF) ? 50%; no uncontrolled angina or active cardiac symptoms consistent with congestive heart failure (class III or IV), by the New York Heart Association criteria; no symptomatic ventricular arrhythmias, or electrocardiogram (ECG) evidence of active ischemia; no evidence by echocardiography of severe valvular stenosis or regurgitation
+Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%; note: testing is required in patients with:\r\n* Age >= 65 years old\r\n* Clinically significant atrial and or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or have a history of ischemic heart disease, chest pain
+History of any of the following within the last 6 months prior to study entry:\r\n* Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures\r\n* Ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures\r\n* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)\r\n* Placement of a pacemaker for control of rhythm\r\n* New York Heart Association (NYHA) class III or IV heart failure\r\n* Pulmonary embolism
+Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) < 6 months prior to screening\r\n* Symptomatic chronic heart failure; evidence of clinically significant cardiac arrhythmias and/or conduction abnormalities < 6 months prior to screening except atrial fibrillation and paroxysmal supraventricular tachycardia
+Patient has active cardiac disease or a history of cardiac dysfunction including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 12 months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening\r\n* Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g. bifascicular block, Mobitz type II and third-degree AV block)\r\n* Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:\r\n** Risk factors for torsades de pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia\r\n** Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause torsades de pointe that cannot be discontinued (within 5 half-lives or 7 days prior to starting study drug) or replaced by safe alternative medication\r\n** Inability to determine the QT interval on screening (QTcF, using Fridericia’s correction)\r\n* Systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg at screening
+Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiography (ECG) abnormality at screening has to be documented by the investigator as not medically relevant\r\n* ECG =< 450 msec for males and =< 470 msec for females required on screening ECG
+History or presence of atrial fibrillation , atrial flutter or paroxysmal supraventricular tachycardia; the presence or history of ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia
+Unstable cardiovascular function: symptomatic ischemia, or uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on antiarrhythmic agents are excluded; 1st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block/right bundle branch block (LAFB/RBBB) will not be excluded), or congestive heart failure (CHF) New York Heart Association (NYHA) class 3, or myocardial infarction (MI) within 3 months; left ventricular ejection fraction < 40%; hypertension > 140 millimeter of mercury (mm Hg) systolic or > 90 mm Hg diastolic with or without antihypertensive therapy
+Significant cardiac conduction abnormalities, including a history of long QTc syndrome and/or pacemaker, or impaired cardiovascular function such as New York Heart Association classification score >2.
+Patient has clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months), such as:\r\n* Unstable angina within 6 months prior to screening\r\n* Myocardial infarction within 6 months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Uncontrolled hypertension defined by a systolic blood pressure (SBP) >= 160 mm Hg and/or diastolic blood pressure (DBP) >= 100 mm Hg, with or without antihypertensive medication \r\n** Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening\r\n* Ventricular arrhythmias; supraventricular and nodal arrhythmias not controlled with medication\r\n* Other cardiac arrhythmia not controlled with medication\r\n* Corrected QT (QTcF) > 470 ms using Fridericia’s correction on the screening electrocardiogram (ECG)
+Other significant electrocardiogram (EKG) abnormalities including second (2nd) degree atrio-ventricular (AV) block type II, third (3rd) degree AV block, or bradycardia (ventricular rate less than 50 beats/min)
+A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), torsade de pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD)
+Any known cardiac abnormalities such as: \r\n* Congenital long QT syndrome \r\n* Corrected QT (QTc) interval >= 485 milliseconds;\r\n* Myocardial infarction within 6 months of course 1 day 1 (C1D1); subjects with a history of myocardial infarction between 6 and 12 months prior to C1D1 who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event may participate;\r\n* Other significant electrocardiogram (ECG) abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min) trial treatments\r\n* Symptomatic coronary artery disease (CAD), e.g., angina; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;\r\n* An ECG recorded at screening showing evidence of cardiac ischemia (ST depression, depression of >= 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;\r\n* Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II to IV definitions and/or ejection fraction < 40% by multi gated acquisition (MUGA) scan or < 50% by echocardiogram and/or magnetic resonance imaging (MRI); \r\n* A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), torsade de pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD); \r\n* Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes; \r\n* Uncontrolled hypertension, i.e., blood pressure (BP) of >= 160/95; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria; or \r\n* Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)\r\n* Patients taking drugs leading to significant QT prolongation
+The subject has a history of any of the following within the last 6 months before administration of the first dose of the drug:\r\n* Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures\r\n* Ischemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures\r\n* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)\r\n* Placement of a pacemaker for control of rhythm\r\n* New York Heart Association (NYHA) class III or IV heart failure\r\n* Significant active cardiovascular or pulmonary disease including:\r\n** Uncontrolled hypertension defined as sustained blood pressure (BP) > 160 mm Hg systolic or > 95 mm Hg diastolic despite optimal antihypertensive treatment\r\n** Pulmonary hypertension\r\n** Uncontrolled asthma or O2 saturation < 90% by arterial blood gas analysis or pulse oximetry on room air\r\n** Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement\r\n** History of arrhythmia requiring an implantable cardiac defibrillator\r\n** Medically significant (symptomatic) bradycardia
+History of myocardial infarction =< 180 days prior to registration or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
+Electrocardiogram (ECG) demonstrating clinically significant arrhythmias that are not adequately medically managed (Note: subjects with chronic atrial arrhythmia, ie, atrial fibrillation or paroxysmal supraventricular tachycardia [SVT], are eligible)
+Myocardial infarction within 6 months prior to enrollment or New York Heart Association class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; if for some reason an electrocardiogram is obtained before study enrollment, any abnormalities detected should be documented as clinically irrelevant
+History or evidence of cardiovascular risk including any of the following:\r\n* LVEF < LLN\r\n* A QT interval corrected for heart rate using the Bazett’s formula QTcB >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization\r\n* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Patients with intra-cardiac defibrillators \r\n* Known cardiac metastases
+Impaired cardiac function or clinically significant cardiac diseases, including any one of the following: \r\n* History or presence of sustained ventricular tachyarrhythmia; (patients with a history of atrial arrhythmia are eligible but should be discussed with Novartis prior to enrollment)\r\n* Any history of ventricular fibrillation or torsade de pointes\r\n* Bradycardia defined as heart rate (HR) < 50 beats per minute (bpm); patients with pacemakers are eligible if HR >= 50 bpm\r\n* Screening electrocardiogram (ECG) with a corrected QT (QTc) > 470 msec\r\n* Right bundle branch block + left anterior hemiblock (bifascicular block)\r\n* Myocardial infarction or unstable angina =< 12 months prior to starting study drug\r\n* Other clinically significant heart disease (e.g., congestive heart failure [CHF] New York [NY] Heart Association class III or IV , uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
+Cardiac conditions as follows: \r\n• Uncontrolled hypertension (BP ? 150/95 mmHg, despite medical therapy) \r\n• Left ventricular ejection fraction (LVEF) < 55%, measured by echocardiography \r\n• Atrial fibrillation with a ventricular rate > 100 bpm on ECG at rest \r\n• Symptomatic heart failure (NYHA grade II-IV) \r\n• Prior or current cardiomyopathy \r\n• Severe valvular heart disease \r\n• Uncontrolled angina (Canadian Cardiovascular Society grade II-IV despite medical therapy) \r\n• Acute coronary syndrome within 6 months prior to starting treatment
+History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia; patients with atrial fibrillation controlled by medication are permitted
+Known clinically significant heart disease as evidenced by:\r\n* Myocardial infarction within 6 months of enrollment\r\n* Uncontrolled angina within 6 months of enrollment\r\n* Congestive heart failure New York Heart Association (NYHA) class III or IV, or a history of congestive heart failure NYHA class III or IV in the past, unless a screening echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) within 3 months results in a left ventricular ejection fraction >= 45%\r\n* Clinically significant ventricular arrhythmias\r\n* History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place\r\n* Bradycardia as indicated by a heart rate < 50 beats per minute at screening visit\r\n* Hypotension as indicated by systolic blood pressure (SBP) =< 85 on 2 consecutive measurements at screening visit\r\n* Uncontrolled hypertension as indicated by SBP > 170 mmHg or diastolic blood pressure (DBP) > 105 mmHg on 2 consecutive measurements at screening visit
+PHASE I STUDY ELIGIBILITY CRITERIA:\r\nPatients who have the following clinical conditions are considered to be at increased risk for cardiac toxicities; patients with any cardiac history of the following conditions within 1 year prior to MEDI+O study or within 2 years prior to MEDI+C or MEDI+O+C enrollment are excluded from the study:\r\n* Prior events including myocardial infarction, clinically significant pericardial effusion, and myocarditis\r\n* Prior cardiac arrhythmia including atrial fibrillation and atrial flutter, or requiring concurrent use of drugs or biologics with pro-arrhythmic potential\r\n* New York Heart Association (NYHA) class II or greater heart failure\r\n* If cardiac function assessment is clinically indicated or performed, an left ventricular ejection fraction (LVEF) less than normal per institutional guidelines, or < 55%, if threshold for normal is not otherwise specified by institutional guidelines\r\n* Mean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia’s correction or other significant ECG abnormality noted within 14 days of treatment\r\n* Hypertensive crisis or hypertensive encephalopathy\r\n* Clinically significant peripheral vascular disease or vascular disease, including rapidly growing aortic aneurysm or abdominal aortic aneurysm > 5 cm or aortic dissection\r\n* Unstable angina
+PHASE II STUDY METASTATIC CASTRATE-RESISTANT PROSTATE CANCER COHORT 4 ELIGIBILITY CRITERIA (MEDI+O ONLY):\r\nThe patient has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:\r\n* Cardiovascular disorders including:\r\n** Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening\r\n** Concurrent uncontrolled hypertension defined as sustained BP >140 mm Hg systolic, or > 90 mm Hg diastolic despite optimal anti-hypertensive treatment (BP must be controlled at screening)\r\n** Any history of congenital long QT syndrome\r\n** Any of the following within 6 months before the first dose of study treatment:\r\n*** Unstable angina pectoris\r\n*** Clinically-significant cardiac arrhythmias with the exception of asymptomatic atrial fibrillation controlled on therapy\r\n*** Stroke (including TIA, or other ischemic event)\r\n*** Myocardial infarction\r\n*** Thromboembolic event requiring therapeutic anti-coagulation (Note: subjects with a venous filter [e.g. vena cava filter] are not eligible for this study)\r\n*** Mean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia’s correction or other significant ECG abnormality noted within 14 days of treatment\r\n* Other clinically significant disorders such as:\r\n** Active infection requiring intravenous treatment within 7 days of starting protocol treatment\r\n** Serious non-healing wound/ulcer/bone fracture (excluding stable compression fracture) within 28 days before the first dose of study treatment
+Uncontrolled clinically significant conduction abnormalities (e.g., ventricular tachycardia on antiarrhythmic agents are excluded; 1st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block/right bundle branch block (LAFB/RBBB) will not be excluded); or
+Uncontrolled intercurrent illness including, but not limited to:\r\n* Ongoing or active infection requiring parenteral antibiotics\r\n* Impairment of lung function (chronic obstructive pulmonary disease [COPD] > grade 2, lung conditions requiring oxygen therapy) or current dyspnea at rest\r\n* Symptomatic congestive heart failure (class III or IV of the New York Heart Association classification for heart disease)\r\n* Known left ventricular ejection fraction (LVEF) < 50%\r\n* Unstable angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months\r\n* Uncontrolled hypertension (systolic blood pressure > 160 mm Hg or diastolic blood pressure > 100 mm Hg, found on two consecutive measurements separated by a 1 or 2-week period despite adequate medical support)\r\n* Clinically significant cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia that is symptomatic or requires treatment [National Cancer Institute-Common Terminology Criteria for Adverse Events, version 4.0, grade 3])\r\n* Corrected QT using the Fridericia correction formula (QTcF) >= 480 msec on screening electrocardiogram (EKG)\r\n* Known history of QT/correct QT (QTc) prolongation or Torsades de Pointes (TdP)\r\n* ST depression or elevation of >= 1.5 mm in 2 or more leads\r\n* Diarrhea of any cause >= Common Terminology Criteria for Adverse Events (CTCAE) grade 2\r\n* Active autoimmune disease that is not controlled by nonsteroidal or steroidal (< 10 mg of prednisone per day) anti-inflammatory drugs or active inflammatory disease, including small or large intestine inflammation such as active Crohn’s disease or ulcerative colitis, which requires immunosuppressive therapy\r\n* Psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements including maintenance of a compliance/pill diary\r\n* Known history of chronic liver disease including cirrhosis, current alcohol abuse, or infection with hepatitis B virus or hepatitis C virus (active or carrier) or renal failure\r\n* Known history of chronic pancreatitis\r\n* Conditions that affect lymphocyte counts, such as human immunodeficiency virus (HIV) infection or immunosuppressive therapy
+Have moderate or severe cardiovascular disease:\r\n* Has the presence of cardiac disease, including a myocardial infarction within six months prior to study entry, unstable angina pectoris, New York Heart Association class III/IV congestive heart failure, or uncontrolled hypertension\r\n* Has documented clinically significant electrocardiography (ECG) abnormalities (not responding to medical treatments) or not clinically stable for at least 6 months\r\n* Has major abnormalities documented by echocardiogram (ECHO) with Doppler (for example, moderate or severe heart valve function defect) that is not stable for at least 6 months; Note: left ventricular [LV] ejection fraction < 50% is allowed only if clinically stable for at least 6 months (evaluation based on the institutional lower limit of normal)\r\n* Has predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress (for example, family history of aneurysms, Marfan-Syndrome, bicuspid aortic valve, evidence of damage to the large vessels of the heart documented by computed tomography [CT] scan/magnetic resonance imaging [MRI] with contrast)
+Patients with New York Heart Association (NYHA) class III and IV heart failure, myocardial infarction in the preceding 6 months, and significant conduction abnormalities, including but not limited to 2nd degree atrioventricular block (AV block) type II, 3rd degree block, QT prolongation (corrected QT [QTc] > 500 millisecond [msec]), sick sinus syndrome, ventricular tachycardia, symptomatic bradycardia (heart rate < 50 beats per minute [bpm]), hypotension, light headedness and syncope; patients with persistent and uncontrolled atrial fibrillation will be excluded; the protocol excludes patients who have recently had a stent and by recommendation of their cardiologist need to stay on anticoagulants such as warfarin or equivalent vitamin K antagonist
+Patients with clinically significant cardiovascular disease: history of ischemic or hemorrhagic stroke within past 6 months; uncontrolled hypertension, on at least 2 repeated determinations on separate days within past 3 months; myocardial infarction or unstable angina within past 6 months; New York Heart Association grade III or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris within past 6 months; clinically significant peripheral vascular disease within past 6 months; pulmonary embolism, deep vein thrombosis (DVT), or other thromboembolic event within past 6 months; diagnosed congenital long QT syndrome; any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes); prolonged QTc interval on pre-entry electrocardiogram (> 450 msec); subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration
+History of myocardial infarction =< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
+A history of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within 6 months or a history or evidence of current clinically significant uncontrolled arrhythmias or intra-cardiac defibrillators or abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram; subjects with grade 1 abnormalities (i.e., mild regurgitations/stenosis) may be entered; subjects with moderate valvular thickening are not eligible; subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible
+History of significant cardiac disease defined as:\r\n* Symptomatic congestive heart failure (CHF) (New York Heart Association [NYHA] classes III-IV)\r\n* High-risk uncontrolled arrhythmias; i.e. atrial tachycardia with a heart rate > 100/min at rest, significant ventricular arrhythmia or higher-grade atrioventricular (AV) block (second degree AV-block type 2 [mobitz 2] or third degree AV-block)\r\n* Prolongation of QT interval > 480 msecs\r\n* History of myocardial infarction within last 12 months\r\n* Clinically significant valvular heart disease\r\n* Angina pectoris requiring anti-angina treatment\r\n* Current uncontrolled hypertension (persistent systolic > 180 mmHg and/or diastolic > 100 mmHg); initiation or adjustment of anti-hypertensive medication is permitted prior to study entry
+Patient has clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months), such as: \r\n* Unstable angina within 6 months prior to screening\r\n* Myocardial infarction within 6 months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Uncontrolled hypertension defined by a systolic blood pressure (SBP) >= 160 mmHg and/or diastolic blood pressure (DBP) >= 100 mmHg, with or without antihypertensive medication - initiation or adjustment of antihypertensive medication(s) is allowed prior to screening\r\n* Ventricular arrhythmias; supraventricular and nodal arrhythmias not controlled with medication\r\n* Other cardiac arrhythmia not controlled with medication\r\n* Corrected QT interval (QTc) > 450 msec using Fridericia correction on the screening electrocardiogram (ECG)
+Unstable angina or myocardial infarction within 6 months prior to enrollment, NYHA class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or grade 3 conduction system abnormalities unless subject has a pacemaker
+History or evidence of cardiovascular risk including any of the following:\r\n* A QT interval corrected for heart rate using the Bazett’s correction formula (QTcB) >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias; exception: subjects with controlled atrial fibrillation for > 30 days prior to taking study drug are eligible\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to taking study drug\r\n* History or evidence of current >= class II congestive heart failure as defined by New York Heart Association\r\n* Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by antihypertensive therapy\r\n* Patients with intra-cardiac defibrillators\r\n* Known cardiac metastases\r\n* Subjects with abnormal left ventricular ejection fraction (< 50%) on echocardiogram or multiple-gated acquisition scan (MUGA)
+Patient has clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months), such as:\r\n* Unstable angina within 6 months prior to screening\r\n* Myocardial infarction within 6 months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Uncontrolled hypertension defined by a systolic blood pressure (SBP) >= 160 mm Hg and/or diastolic blood pressure (DBP) >= 100 mm Hg, with or without antihypertensive medication \r\n* Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening\r\n* Ventricular arrhythmias\r\n* Supraventricular and nodal arrhythmias not controlled with medication\r\n* Other cardiac arrhythmia not controlled with medication\r\n* Corrected QTcF > 470 msec using Fridericia correction on the screening electrocardiogram (ECG)
+Patient has active cardiac disease including any of the following: \r\n* Corrected QT (QTc) > 500 msec on screening electrocardiogram (ECG) (using the QTc Fridericia [F] formula)\r\n* Angina pectoris that requires the use of anti-anginal medication\r\n* Ventricular arrhythmias except for benign premature ventricular contractions\r\n* Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication\r\n* Conduction abnormality requiring a pacemaker\r\n* Valvular disease with document compromise in cardiac function\r\n* Symptomatic pericarditis
+Patient has a history of cardiac dysfunction including any of the following:\r\n* Myocardial infraction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular ejection fraction (LVEF) function\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy
+Unstable cardiovascular function defined as symptomatic ischemia, uncontrolled clinically significant conduction abnormalities (i.e.: ventricular tachycardia on antiarrhythmics are excluded and first [1st] degree atrioventricular [AV] block or asymptomatic left anterior fascicular block [LAFB]/right bundle branch block [RBBB] will not be excluded), congestive heart failure (CHF) of New York Heart Association (NYHA) class >= 3, or myocardial infarction (MI) within 3 months
+Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study; impaired cardiac function or clinically significant cardiac diseases, including any of the following:\r\n* Unstable angina within 6 months prior to screening\r\n* Myocardial infarction within 6 months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III - IV)\r\n* Uncontrolled hypertension defined by a systolic blood pressure (SBP) >= 160 mm Hg and/or diastolic blood pressure (DBP) >= 100 mm Hg, with or without antihypertensive medication\r\n* Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening\r\n* Ventricular arrhythmias; supraventricular and nodal arrhythmias not controlled with medication\r\n* Other cardiac arrhythmia not controlled with medication\r\n* Corrected QT (QTc) > 450 msec using Fridericia correction on the screening electrocardiogram (ECG)
+Current, serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute arrhythmia or ventricular arrhythmias classified as Lown III, IV or V (Appendix F).
+Myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
+Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%; testing is required in patients who are:\r\n* Age >= 65 years old\r\n* Clinically significant atrial and or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or have a history of ischemic heart disease, or chest pain
+History or evidence of cardiovascular risk including any of the following:\r\n* Left ventricular ejection fraction (LVEF) < LLN\r\n* A QT interval corrected for heart rate using the Bazett’s formula (QTcB) >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization\r\n* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Patients with intra-cardiac defibrillators\r\n* Known cardiac metastases
+Patient has active cardiac disease including any of the following:\r\n* Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* Corrected QT (QTc) interval > 480 msec on screening electrocardiogram (ECG) (using the QTc Fridericia [F] formula)\r\n* Angina pectoris that requires the use of anti-anginal medication\r\n* Ventricular arrhythmias except for benign premature ventricular contractions\r\n* Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication\r\n* Conduction abnormality requiring a pacemaker\r\n* Valvular disease with document compromise in cardiac function\r\n* Symptomatic pericarditis
+Documented left ventricular ejection fraction (LVEF) of less than or equal to 45% testing is required in patients who are\r\n* >= 65 years old\r\n* Clinically significant atrial and or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or have a history of ischemic heart disease, or chest pain
+Impaired cardiac function or clinically significant cardiac diseases, including any of the following: history or presence of ventricular tachyarrhythmia; presence of unstable atrial fibrillation (ventricular response > 100 beats per minute [bpm]); patients with stable atrial fibrillation are eligible, provided they do not meet any of the other cardiac exclusion criteria; clinically significant resting bradycardia (< 50 bpm); angina pectoris or acute myocardial infarction =< 3 months prior to starting study drug; other clinically significant heart disease (e.g., symptomatic congestive heart failure; uncontrolled arrhythmia or hypertension; history of labile hypertension or poor compliance with an antihypertensive regimen)
+History or evidence of cardiovascular risk including any of the following:\r\n* An average of the three most recent QT intervals corrected for heart rate using the Bazett’s formula QTcB >= 460 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization\r\n* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study\r\n* Prior placement of an implantable defibrillator\r\n* History of or identification on screening imaging of intracardiac metastases
+Has significant cardiac conduction abnormalities and/ or pacemaker or any of the following criteria:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft [CABG], coronary angioplasty, or stenting) < 6 months prior to screening\r\n* Symptomatic chronic heart failure; evidence of clinically significant cardiac arrhythmias and/or conduction abnormalities < 6 months prior to screening\r\n* Uncontrolled arterial hypertension, defined as blood pressure (BP) > 140/100 mmHg (average of 3 consecutive readings)
+History or evidence of cardiovascular risk including any of the following:\r\n* Left ventricle ejection fraction (LVEF) < LLN\r\n* A QT interval corrected for heart rate using the Bazett’s formula QTcB >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to enrollment are eligible)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization\r\n* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Known cardiac metastases\r\n* Patients with intra-cardiac defibrillators
+New York Heart Association classification III or IV, known symptomatic coronary artery disease, or symptoms of coronary artery disease on systems review, or known cardiac arrhythmias (atrial fibrillation or supraventricular tachycardia [SVT])
+Unstable angina or myocardial infarction within 4 months prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or grade 3 conduction system abnormalities unless subject has a pacemaker
+Patients have clinically significant cardiovascular disease, including any of the following: \r\n* History of acute coronary syndrome including myocardial infarction, unstable angina, coronary artery bypass graft (CABG), coronary angioplasty or stenting < 6 months prior to screening\r\n* Symptomatic chronic heart failure (New York Heart Association criteria, class II-IV)\r\n* Evidence of clinically significant cardiac arrhythmias and/or conduction abnormalities < 6 months prior to screening except atrial fibrillation (AF) and paroxysmal supraventricular tachycardia (PSVT)
+Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%; testing is required in patients with:\r\n* Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block, chest pain, or ischemic heart disease\r\n* Age >= 65 years old
+Myocardial infarct within 6 months before enrollment, New York Heart Association (NYHA) class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemia
+Must not have had any unstable angina or myocardial infarction within 4 months prior to enrollment, NYHA Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker.
+Uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiogram (EKG) suggestive of acute ischemia or active conduction system abnormalities
+RANDOMIZED PHASE II (ARMS K AND L): Patients must not have NYHA class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia
+RANDOMIZED PHASE II (ARMS K AND L): Patients must not have a history of or evidence of cardiovascular risks including any of the following:\r\n* QT interval corrected for heart rate using the Bazett’s formula QTcB >= 480 msec at baseline \r\n* History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within the past 24 weeks prior to registration\r\n* History prior to registration or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Left ventricular ejection fraction (LVEF) =< lower limit of normal on cardiac echocardiogram (echo) or multigated acquisition scan (MUGA)\r\n* Intra-cardiac defibrillator\r\n* History of abnormal cardiac valve morphology (>= grade 2) documented by ECHO; (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study\r\n* History or evidence of current clinically significant uncontrolled cardiac arrhythmias; clarification: subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible\r\n* Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy
+Impaired cardiac function including any of the following: Screening ECG with a QTc >450 msec. The QTc interval will be calculated by Fridericia's correction factor (QTcF) at Screening and on Day 5 prior to the first dose of AC220. The QTcF will be derived from the average QTcF in triplicate.; If QTcF>450 msec on Day 5, AC220 will not be given; Patients with congenital long QT syndrome; History or presence of sustained ventricular tachycardia requiring medical intervention; Any history of clinically significant ventricular fibrillation or torsades de pointes; Known history of second or third degree heart block (may be eligible if the patient currently has a pacemaker); Sustained heart rate of <50/minute on pre-entry ECG; Right bundle branch block + left anterior hemiblock (bifascicular block); Patients with myocardial infarction or unstable angina within 6 months prior to starting study drug; CHF NY Heart Association class III or IV.
+Relapsed/refractory MCL: Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block, bradycardia (< 50 beats per minute [bpm]), or corrected QT (QTc) > 500 msec
+Newly diagnosed MCL: Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree AV block type II, 3rd degree block, bradycardia (< 50 bpm), or QTc > 500 msec
+Any history of ventricular fibrillation or torsades de pointes
+Patient do not have adequate cardiac function defined as:\r\n* Left ventricular ejection fraction (LVEF) =< 50% as determined by a multigated acquisition (MUGA) scan or echocardiogram\r\n* Corrected QT (QTc) interval >= 480 ms\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting [CABG], coronary angioplasty, or stenting) < 6 months prior to screening\r\n* Symptomatic chronic heart failure; evidence of clinically significant cardiac arrhythmias and/or conduction abnormalities < 6 months prior to screening
+Since IL-2 is administered following cell infusion:\r\n* Patients will be excluded if they have a history of clinically significant electrocardiogram (ECG) abnormalities, symptoms of cardiac ischemia or arrhythmias and have a left ventricular ejection fraction (LVEF) < 45% on a cardiac stress test (stress thallium, stress multigated acquisition scan [MUGA], dobutamine echocardiogram, or other stress test) \r\n* Similarly, patients who are 50 years old with a baseline LVEF < 45% will be excluded\r\n* Patients with ECG results of any conduction delays (PR interval > 200 ms, corrected QT interval [QTC] > 480 ms), sinus bradycardia (resting heart rate < 50 beats per minute), sinus tachycardia (heart rate [HR] > 120 beats per minute) will be evaluated by a cardiologist prior to starting the trial; patients with any arrhythmias, including atrial fibrillation/atrial flutter, excessive ectopy (defined as > 20 premature ventricular contractions [PVCs] per minute), ventricular tachycardia, third (3rd) degree heart block will be excluded from the study unless cleared by a cardiologist\r\n* Patients with pulmonary function test abnormalities as evidenced by a forced ejection volume in 1 second (FEV1)/forced vital capacity (FVC) < 70% of predicted for normality will be excluded
+Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
+Ponatinib\r\n* History of acute pancreatitis within 1 year of study or history of chronic pancreatitis\r\n* History of alcohol abuse\r\n* Uncontrolled hypertriglyceridemia (triglycerides > 450 mg/dL)\r\n* Clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:\r\n** Any history of myocardial infarction, stroke, or revascularization\r\n** Unstable angina or transient ischemic attack within 6 months prior to start of study treatment\r\n** Congestive heart failure within 6 months prior to enrollment, or left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards within 6 months prior to enrollment\r\n** History of clinically significant (as determined by the treating physician) atrial arrhythmia\r\n** Any history of ventricular arrhythmia\r\n** Any history of venous thromboembolism including deep venous thrombosis or pulmonary embolism\r\n* Uncontrolled hypertension (diastolic blood pressure > 90 mm Hg; systolic > 140 mm Hg); patients with hypertension should be under treatment on study entry to effect blood pressure control; taking medications that are known to be associated with torsades de pointes\r\n* Taking any medications or herbal supplements that are known to be strong inhibitors of CYP3A4 within at least 14 days before the first dose of ponatinib\r\n* Ocular toxicity present as measured during a comprehensive eye exam
+Concurrent medical condition which may increase the risk of toxicity, including:\r\n* Pleural or pericardial effusion of any grade at the time of screening for study\r\n* Cardiac symptoms; any of the following should be considered for exclusion:\r\n** Uncontrolled angina, congestive heart failure or myocardial infarction (MI) (within 6 months)\r\n** Diagnosed congenital long QT syndrome\r\n** Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes)\r\n** Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (> 450 msec)
+Cardiac disease including: uncontrolled angina within 3 months; diagnosed or suspected congenital long QT syndrome; any history of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or Torsades de pointes); prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (> 470 msec) on the Fridericia's correction; uncontrolled hypertension (defined for this protocol as sustained systolic blood pressure [BP] >= 150 and diastolic >= 100); patients currently taking drugs that are generally accepted to have a risk of causing Torsades de pointes
+Documented LVEF =< 45% tested in patients:\r\n* Age >= 65 years\r\n* With clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second-or third-degree heart block or have a history of ischemic heart disease and/or chest pain
+Clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to: \r\n* Any history of myocardial infarction (MI), stroke, or revascularization\r\n* Unstable angina or transient ischemic attack prior to enrollment \r\n* Congestive heart failure prior to enrollment, or left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards prior to enrollment \r\n* Diagnosed or suspected congenital long QT syndrome \r\n* Any history of clinically significant atrial or ventricular arrhythmias (such as atrial fibrillation, ventricular tachycardia, ventricular fibrillation, or torsades de pointes) as determined by the treating physician\r\n* Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (> 470 msec) unless corrected after electrolyte replacement\r\n* Any history of venous thromboembolism including deep venous thrombosis or pulmonary embolism\r\n* Uncontrolled hypertension (diastolic blood pressure > 90 mmHg; systolic > 140 mmHg); patients with hypertension should be under treatment on study entry to effect blood pressure control
+The following cardiac abnormalities:\r\n* Congenital long QT syndrome\r\n* Corrected QT (QTc)/ Fridericia's correction QT (QTf) interval >= 480 milliseconds; unless secondary to pacemaker or bundle branch block\r\n* Myocardial infarction within 6 months (subjects with a history of myocardial infarction within the last 6 to 12 months who are asymptomatic and have had a negative cardiac risk assessment [treadmill stress test, nuclear medicine stress test, or stress echocardiogram] since the event may participate)\r\n* Other significant electrocardiogram (ECG) abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block\r\n* Symptomatic coronary artery disease (CAD), e.g. angina Canadian class II-IV; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present\r\n* An ECG recorded at screening showing evidence of cardiac ischemia (ST depression of >= 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the patient should have a stress imaging study and. if abnormal, angiography to define whether or not CAD is present\r\n* Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II to IV and/or ejection fraction < 45% by multigated acquisition (MUGA), echocardiogram, or cardiac magnetic resonance imaging (MRI)\r\n* A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), torsade de pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD)\r\n* Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes\r\n* Uncontrolled hypertension, i.e., blood pressure (BP) of >= 170/95; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month prior to study registration) and meet all other inclusion criteria\r\n* Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)\r\n* For patients enrolling on the romidepsin arm; taking drugs associated with significant QTc/QTf prolongation, unless able to be switched to non-QTc/QTf prolonging medication or on a stable dose without significant QT prolongation (> 470 msec)\r\n** Caution should be used when administering study drugs to patients taking medications significantly metabolized by these enzymes; particular attention should be paid to patients receiving warfarin; patients should have coagulation parameters monitored regularly, and warfarin dose adjusted accordingly; if these drugs cannot be discontinued or replaced, enrollment may be allowed after discussion with MSK principle investigator (PI)
+Cardiac conditions as follows:\r\n* Uncontrolled hypertension (blood pressure [BP] >=150/95 mmHg despite medical therapy)\r\n* Left ventricular ejection fraction < 55% measured by echocardiography\r\n* Atrial fibrillation with a ventricular rate > 100 beats per minute (bpm) on electrocardiogram (ECG) at rest\r\n* Symptomatic heart failure (New York Heart Association [NYHA] grade II-IV)\r\n* Prior or current cardiomyopathy\r\n* Severe valvular heart disease\r\n* Uncontrolled angina (Canadian Cardiovascular Society grade II-IV despite medical therapy)\r\n* Acute coronary syndrome =< 6 months prior to registration
+Any known cardiac abnormalities such as:\r\n* Congenital long QT syndrome\r\n* Corrected QT (QTc) interval >= 500 milliseconds\r\n* Myocardial infarction within 6 months of transplantation; subjects with a history of myocardial infarction between 6 and 12 months prior to transplant who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event may participate\r\n* Other significant electrocardiogram (ECG) abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min)\r\n* Symptomatic coronary artery disease (CAD), e.g., angina Canadian class II-IV; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present\r\n* An ECG recorded at screening showing evidence of cardiac ischemia (ST depression of >= 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present\r\n* Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II to IV definitions and/or ejection fraction < 40% by multi gated acquisition (MUGA) scan or < 50% by echocardiogram and/or magnetic resonance imaging (MRI)\r\n* A known history or sustained ventricular tachycardia (VT), ventricular fibrillation (VF), torsade de pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD)\r\n* Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes\r\n* Uncontrolled hypertension, defined as blood pressure (BP) >= 160/95; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria\r\n* Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)\r\n* Patients taking drugs leading to significant QT prolongation within the specified wash out period\r\n* Concomitant use of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors
+Uncontrolled intercurrent illnesses including, but not limited to unstable angina or uncontrolled cardiac arrhythmia, chronic liver disease, complete left bundle branch block, obligate use of a cardiac pacemaker, ST depression of > 1 mm in two or more leads and/or T wave inversions in two or more contiguous leads, congenital long QT syndrome, history of or presence of significant ventricular or atrial tachyarrhythmias, clinically significant resting bradycardia (< 50 beats per minute), corrected QT (QTc) > 480 ms on screening electrocardiogram that could jeopardize the patient’s ability to receive the chemotherapy described in the protocol safely
+History of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation or Torsades de Pointes);
+Any clinically relevant abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third-degree heart block, second-degree heart block, PR interval >250 msec).
+Known cardiopulmonary disease defined as:\r\n* Unstable angina\r\n* Congestive heart failure (New York Heart Association class III or IV)\r\n* Myocardial infarction (MI) within 6 months prior to first dose of pevonedistat (patients who had ischemic heart disease resulting in MI and/or revascularization greater than 6 months before treatment and who are without cardiac symptoms may enroll)\r\n* Cardiomyopathy\r\n* Left ventricular ejection fraction < 50% as assessed by echocardiogram or radionuclide angiography\r\n* Clinically significant arrhythmia:\r\n** History of polymorphic ventricular fibrillation or torsade de pointes\r\n** Permanent atrial fibrillation [a fib], defined as continuous a fib for >= 6 months\r\n** Persistent a fib, defined as sustained a fib lasting > 7 days and/or requiring cardioversion in the 4 weeks before screening\r\n** Grade 3 a fib defined as symptomatic and incompletely controlled medically, or controlled with device (e.g. pacemaker), or ablation and \r\n** Patients with paroxysmal a fib or < grade (Gr) 3 a fib for period of at least 6 months are permitted to enroll provided that their rate is controlled on a stable regimen\r\n* Implantable cardioverter defibrillator\r\n* Moderate to severe aortic and/or mitral stenosis or other valvulopathy (ongoing)\r\n* Pulmonary hypertension
+Class II or greater New York Heart Association Functional Classification criteria or serious cardiac arrhythmias likely to increase the risk of cardiac complications of cytokine therapy (e.g. ventricular tachycardia, frequent ventricular ectopy, or supraventricular tachyarrhythmia requiring chronic therapy)
+Clinically significant cardiovascular disease including:\r\n* LVEF < 45% measured by echocardiogram\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months\r\n* Uncontrolled angina within 3 months\r\n* New York Heart Association (NYHA) class III or IV congestive heart failure\r\n* Clinically significant abnormality on EKG\r\n* History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes)\r\n* Patients with intra-cardiac defibrillators or permanent pacemakers
+History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsade de pointes);
+Subject has had myocardial infarction within 6 months prior to enrollment , or NYHA(New York Hospital Association) Class III or IV heart failure (see APPENDIX VI), Ejection Fraction < 35%, uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
+Unstable angina or myocardial infarction within 4 months prior to randomization, New York Heart Association (NYHA) class III or IV heart failure, left ventricular ejection fraction (LVEF) < 40%, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias including uncontrolled chronic atrial fibrillation/atrial flutter, history of torsades de pointe, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or grade 3 conduction system abnormalities unless subject has a pacemaker
+Patients who have had any of the following cardiac conditions are NOT eligible for participation (unless otherwise noted):\r\n* Unstable angina or myocardial infarction within 4 months prior to registration\r\n* New York Heart Association (NYHA) class III or IV heart failure\r\n* Uncontrolled angina\r\n* A history of severe coronary artery disease\r\n* Severe, uncontrolled ventricular arrhythmias\r\n* Sick sinus syndrome\r\n* Electrocardiographic evidence of acute ischemia or grade 3 conduction system abnormalities UNLESS the patient has a pacemaker
+Patient had a myocardial infarction within 6 months of enrollment or has NYHA Class III or IV heart failure uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
+Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:\r\n* ST depression or elevation of >= 1.5 mm in 2 or more leads\r\n* Congenital long QT syndrome\r\n* History or presence of ventricular arrhythmias or atrial fibrillation\r\n* Clinically significant resting bradycardia (< 50 beats per minutes)\r\n* Complete left bundle branch block\r\n* Right bundle branch block + left anterior hemiblock (bifascicular block)
+Patient has active cardiac disease including any of the following:\r\n* Left ventricular ejection fraction (LVEF) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* Corrected QT (QTc) > 480 msec on screening electrocardiogram (ECG) (using the QT with Fridericia’s Correction [QTcF])\r\n* Angina pectoris that requires the use of anti-anginal medication\r\n* Ventricular arrhythmias except for benign premature ventricular contractions\r\n* Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication\r\n* Conduction abnormality requiring a pacemaker\r\n* Valvular disease with document compromise in cardiac function\r\n* Symptomatic pericarditis
+Evidence of cardiovascular risk including any of the following: Corrected QT interval Fridericia (QTcF) interval >=470 milliseconds (msecs); Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (Type II) or 3rd degree atrioventricular (AV) block; History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within six months of Screening; Class III or IV heart failure as defined by the New York Heart Association functional classification system (NYHA); Uncontrolled hypertension.
+Any of the following cardiac diseases currently or within the last 6 months as defined by New York Heart Association (NYHA) >= class 2\r\n* Unstable angina pectoris\r\n* Congestive heart failure\r\n* Acute myocardial infarction\r\n* Conduction abnormality not controlled with pacemaker or medication\r\n* Significant ventricular or supraventricular arrhythmias (patients with chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible)
+Evidence of cardiovascular risk including any of the following: a. Corrected QT (QTc) interval >=470 millisecond (msec); Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant ECG abnormalities including 2nd degree (Type II) or 3rd degree atrioventricular (AV) block; History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within six months of Screening; Class III or IV heart failure as defined by the New York Heart Association functional classification system; Uncontrolled hypertension.
+Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following within 6 months of enrollment: myocardial infarction, unstable angina, coronary artery bypass graft (CABG), coronary angioplasty, or stenting, symptomatic chronic heart failure, clinically significant cardiac arrhythmias and/or conduction (except atrial fibrillation and paroxysmal supraventricular tachycardia)
+Any of the following cardiac diseases currently or within the last 6 months as defined by New York Heart Association (NYHA) >= class 2. a. Unstable angina pectoris; b. Congestive heart failure; c. Acute myocardial infarction; d. Conduction abnormality not controlled with pacemaker or medication; e. Significant ventricular or supraventricular arrhythmias (patients with chronic rate- controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible).
+History of myocardial infarction ? 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
+Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:\r\n* Myocardial infarction or stroke/transient ischemic attack within the past 6 months\r\n* Uncontrolled angina within the past 3 months\r\n* Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)\r\n* QT interval corrected for heart rate using Fridericia’s formula (QTcF) prolongation > 480 msec\r\n* History of other clinically significant heart disease (e.g. cardiomyopathy, congestive heart failure with New York Heart Association [NYHA] functional classification III-IV, pericarditis, significant pericardial effusion, or myocarditis)
+Known cardiopulmonary disease defined as one of the following:\r\n* Unstable angina\r\n* Uncontrolled high blood pressure (ie, systolic blood pressure > 180 mmHg, diastolic blood pressure > 95 mm Hg )\r\n* Congestive heart failure (New York Heart Association [NYHA] class III or IV)\r\n* Myocardial infarction (MI) within 6 months prior to first dose (patients who had ischemic heart disease such as a (acute chest syndrome [ACS]), MI, and/or revascularization greater than 6 months before screening and who are without cardiac symptoms may enroll)\r\n* Cardiomyopathy\r\n* Clinically significant arrhythmia: 1) History of polymorphic ventricular fibrillation or torsade de pointes, 2) Permanent atrial fibrillation [a fib], defined as continuous a fib for >= 6 months, 3) Persistent a fib, defined as sustained a fib lasting > 7 days and/or requiring cardioversion in the 4 weeks before screening, 4) grade 3 a fib defined as symptomatic and incompletely controlled medically, or controlled with device (e.g. pacemaker), or ablation and 5) Patients with paroxysmal a fib or < grade (Gr) 3 a fib for period of at least 6 months are permitted to enroll provided that their rate is controlled on a stable regimen\r\n* Implantable cardioverter defibrillator\r\n* Moderate to severe aortic and/or mitral stenosis or other valvulopathy (ongoing)\r\n* Pulmonary hypertension\r\n* Prolong rate corrected QT (QTc) interval >= 500 msec. calculated according to institutional guidelines\r\n* Left ventricular ejection fraction (LVEF) ? 50% as assessed by echocardiogram or radionuclide angiography
+Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%; note: testing is required in patients with:\r\n* Age >= 65 years’ old\r\n* Clinically significant atrial and or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or have a history of ischemic heart disease, chest pain
+Any other clinically significant heart disease, including angina pectoris, resting bradycardia, left bundle branch block, ventricular tachyarrhythmia, unstable atrial fibrillation, acute myocardial infarction, or heart disease requiring cardiac pacemaker or implantable cardioverter/defibrillator
+Patients with history of myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
+Within 14 days of study registration (30 days for pulmonary and cardiac): left ventricular ejection fraction (LVEF) >= 40% by echocardiography or multigated acquisition (MUGA), no uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
+History of myocardial infarction =< 180 days (6 months), or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
+Active cardiac conditions, including any of the following:\r\n* Uncontrolled hypertension (blood pressure [BP] > 150/95 mmHg despite medical therapy)\r\n* Acute coronary syndrome within 6 months prior to starting treatment\r\n* Uncontrolled angina despite medical therapy\r\n* Symptomatic heart failure (New York Heart Association [NYHA] class II-IV despite medical therapy)\r\n* Baseline left ventricular ejection fraction (LV EF) < 50% measured by either echocardiography or multigated acquisition (MUGA) scan\r\n* Severe valvular heart disease\r\n* Atrial fibrillation with ventricular rate > 100 beats per minute (bpm) on electrocardiogram (EKG) at rest
+Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular block (AV block) type II, 3rd degree block, bradycardia (< 50 beats per minute [bpm]), or corrected QT (QTc) > 500 msec.
+Patient has known clinically significant cardiac disease or impaired cardiac function, such as:\r\n* Congestive heart failure requiring treatment (New York Heart Association grade >= 2), left ventricular ejection fraction (LVEF) < 50% as determined by multigated acquisition (MUGA) scan or ECHO. \r\n* History or current evidence of clinically significant cardiac arrhythmias, atrial fibrillation, and/or conduction abnormality, e.g., congenital long QT syndrome, high-grade/complete arteriovenous blockage.\r\n* Acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft, coronary angioplasty, or stenting) < 3 months prior to screening.
+Impaired cardiac function or clinically significant cardiac disease, as defined: a) left ventricular ejection fraction < lower limit of normal (LLN) on multiple gated acquisition scan (MUGA) or echocardiogram; b) congenital long QT syndrome or family history of unexpected sudden cardiac death; c) corrected QT (QTc) corrected with Bazett’s formula (QTcB) >= 480 ms.; d) history or evidence of current clinically significant uncontrolled arrhythmias; note subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible; e) history of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization; f) history or evidence of current >= class II congestive heart failure as defined by New York Heart Association (NYHA); g) treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy; h) patients with intra-cardiac defibrillators
+Patients will be ineligible for treatment on this protocol if (prior to protocol entry):\r\n* There is a history of a recent (within one year) myocardial infarction\r\n* There is a current or prior history of angina/coronary symptoms requiring medications and/or evidence of depressed left ventricular function (LVEF < 45% by MUGA or ECHO)\r\n* There is clinical evidence of congestive heart failure requiring medical management (irrespective of MUGA or ECHO results)
+Patient has clinically significant cardiac disease or impaired cardiac function, such as:\r\n* Congestive heart failure (CHF) requiring treatment (New York Heart Association [NYHA] Grade >= 2), left ventricular ejection fraction (LVEF) < 50% as determined by multi-gated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* History or current evidence of clinically significant cardiac arrhythmias, atrial fibrillation and/or conduction abnormality, e.g. congenital long QT syndrome, high-grade/complete atrioventricular (AV)-blockage; patients with asymptomatic and rate-controlled atrial fibrillation are not excluded\r\n* Acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft (CABG), coronary angioplasty, or stenting), < 3 months prior to screening
+Cardiac abnormalities as evidenced by any of the following: Baseline QT interval corrected for heart rate by Fridericia's formula (QTcF) interval >=450 milliseconds (msec), clinically significant conduction abnormalities or arrhythmias, such as subjects with second degree (Type II) or third degree atrio-ventricular block, history or evidence of current ?Class II congestive heart failure as defined by New York Heart Association (NYHA), history of acute coronary syndromes (including unstable angina and myocardial infarction), coronary angioplasty, or stenting within the past 3 months. Subjects with a history of stent placement requiring ongoing anti-coagulant therapy (e.g., clopidogrel, prasugrel) will not be permitted to enroll, known cardiac metastasis.
+Participant has a history of cardiac dysfunction including any of the following:\r\n* Myocardial infarction within the last 6 months prior to start of study drug, documents by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular ejection fraction (LVEF) function\r\n* History of documents congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Congenital long QT syndrome
+Cardiac disease that would preclude the use of any of the drugs included in the GI002 treatment regimen; this includes but is not limited to:\r\n* Clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or indwelling temporary pacemaker\r\n* Ventricular tachycardia or supraventricular tachycardia that requires treatment with class Ia antiarrhythmic drugs (e.g., quinidine, procainamide, disopyramide) or class III antiarrhythmic drug (e.g., sotalol, amiodarone, dofetilide); use of other antiarrhythmic drugs is permitted\r\n* Second- or third-degree atrioventricular (AV) block unless treated with a permanent pacemaker\r\n* Complete left bundle branch block (LBBB)\r\n* History of long QT syndrome\r\n* Corrected QT (QTc) >= 450ms
+Significant cardiac disease or abnormality, including any one of the following:\r\n* Left ventricular ejection fraction < 50% at screening (assessed by echocardiography, cardiac MRI or multigated acquisition [MUGA])\r\n* Corrected QT Fridericia's correction formula (QTcF) > 470 ms on screening electrocardiogram (ECG), or a clinically-relevant ECG abnormality\r\n* Congenital long QT syndrome\r\n* History of sustained ventricular tachycardia, ventricular fibrillation, or torsades de pointes\r\n* Presence of atrial fibrillation with tachyarrhythmia (ventricular response rate > 100 beats per minute [bpm])\r\n* Bradycardia (heart rate < 50 bpm)\r\n* Complete left bundle branch block\r\n* Bifascicular block (complete right bundle branch block and anterior or posterior left hemiblock)\r\n* Myocardial infarction, acute coronary syndrome (including unstable angina), coronary revascularization procedures, or coronary arterial bypass grafting within the 6 months prior to starting study drug\r\n* Cardiac troponin (either troponin T or troponin I) > ULN\r\n* Congestive heart failure of New York Heart Association class III or IV\r\n* Unstable angina pectoris
+History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
+Impaired cardiovascular function or clinically specific cardiovascular disease including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) =< 6 months; OR\r\n* Symptomatic chronic heart failure history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality < 6 months prior to screening; except atrial fibrillation and paroxysmal supraventricular tachycardia
+Patients with the following cardiac conditions are excluded:\r\n* Uncontrolled hypertension (blood pressure [BP] of >= 150/95 despite medical support/management)\r\n* Acute coronary syndrome within 6 months prior to starting treatment\r\n* Uncontrolled angina – Canadian Cardiovascular Society grade II-IV despite medical support/management\r\n* Heart failure New York Heart Association (NYHA) class II or above\r\n* Prior or current cardiomyopathy (within 6 months) including but not limited to the following:\r\n** Known hypertrophic cardiomyopathy\r\n** Known arrhythmogenic right ventricular cardiomyopathy\r\n** Abnormal ejection fraction (echocardiogram [ECHO]) =< 53% (if a range is given then the upper value of the range will be used) or cardiac MRI\r\n** Previous moderate or severe impairment of left ventricular systolic function (left ventricular ejection fraction [LVEF] < 45% on echocardiography or equivalent on multi-gated acquisition scan [MUGA]) even if full recovery has occurred; echocardiogram (Echo) and additional cardiac studies not indicated unless clinically symptomatic or patient has significant cardiac history\r\n** Severe valvular heart disease\r\n** Atrial fibrillation with a ventricular rate > 100 beats per minute (bpm) on electrocardiogram (ECG) at rest\r\n** Fridericia's corrected QT interval (QTcF) >= 450 msec or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) are excluded; the use of medication(s) that can prolong QTc interval is prohibited while treated on this study
+Patients with clinically significant cardiovascular disease; this includes:\r\n* Myocardial infarction or unstable angina within 6 months prior to registration\r\n* New York heart association (NYHA) class II or greater congestive heart failure\r\n* History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or serious cardiac arrhythmia requiring medication; this does not include asymptomatic atrial fibrillation with controlled ventricular rate\r\n* Any history of congenital long QT syndrome\r\n* The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before randomization; Note: if initial QTcF is found to be > 500 ms, two additional electrocardiogram (EKGs) separated by at least 3 minutes should be performed; if the average of these three consecutive results for QTcF is =< 500 ms, the subject meets eligibility in this regard
+Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure (New York Heart Association [NYHA] class III or IV), unstable angina pectoris, myocardial infarction within 6 months prior to enrollment, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
+History or evidence of cardiovascular risks, except stable ECD cardiac lesion, including any of the following:\r\n* QT interval corrected for heart rate using the Bazett’s formula (QTcB) >= 480 msec\r\n* History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within the past 24 weeks prior to randomization\r\n* History or evidence of current class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Intra-cardiac defibrillators\r\n* Abnormal cardiac valve morphology (>= grade 2) documented by ECHO; (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study\r\n* History or evidence of current clinically significant uncontrolled cardiac arrhythmias; clarification: subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible\r\n* Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy
+History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (Common Terminology Criteria for Adverse Events [CTCAE] grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia; patients with atrial fibrillation controlled by medication are permitted
+History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
+Patients with a history of cardiac disease are excluded: myocardial infarction or arterial thromboembolic events within 6 months prior to baseline, severe or unstable angina, New York Heart Association Class III or IV disease, QTCB (corrected according to Bazett's formula) interval > 470 msec, serious uncontrolled hypertension (systolic > 150 and/or diastolic > 100 mm Hg); baseline electrocardiography, echocardiography and assessment of serum troponin (I) are included in the screening exams; subjects in whom these assays are abnormal (electrocardiogram [EKG] excluding 1st degree branch block, sinus brachycardia, sinus tachycardia or non-specific T wave changes, serum troponin >= grade 2) are ineligible
+Patient has a history of cardiac dysfunction or disease including any of the following:\r\n* Myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular ejection fraction (LVEF) function\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV) or documented cardiomyopathy\r\n* Corrected QT (QTc) interval > 470 msec on screening electrocardiogram (EKG) (using the QTc-Fridericia [QTcF] formula)\r\n* Angina pectoris that requires the use of anti-anginal medication\r\n* Ventricular arrhythmias except for benign premature ventricular contractions\r\n* Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medications\r\n* Conduction abnormality requiring a pacemaker\r\n* Valvular disease with documented compromise in cardiac function\r\n* Known history of QT/QTc prolongation or torsades de pointes (TdP); patients who are currently receiving treatment with medication with a known risk to prolong the QT interval or inducing torsades de pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drugs\r\n* Symptomatic pericarditis\r\n* ST depression or elevation of >= 1.5 mm in 2 or more leads
+Patients who have congestive heart failure (New York Heart Association [NYHA] class III or IV), unstable angina, sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block or a history of acute myocardial infarction within the six months preceding enrollment
+Class II or greater congestive heart failure as described in the New York Heart Association Functional Classification criteria or serious arrhythmias likely to increase the risk of cardiac complications of cytokine therapy (e.g. ventricular tachycardia, frequent ventricular ectopy, or supraventricular tachyarrhythmias requiring chronic therapy)
+Patients who have congestive heart failure (New York Heart Association [NYHA] class III or IV), unstable angina, sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block or a history of acute myocardial infarction (MI) within 6 months of study registration
+Clinically significant, uncontrolled heart disease and/or a recent events including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 12 months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Patient has a Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening\r\n* History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, conduction abnormality in the previous 12 months of screening\r\n* Congenital long QT syndrome or family history of long QT syndrome\r\n* Sustained systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg at screening; must be corrected or controlled prior to starting study\r\n* Bradycardia (heart rate < 50 at rest) by electrocardiogram (ECG) or pulse, at screening\r\n* On screening inability to determine the QTcF interval on the ECG (i.e.: unreadable or not interpretable) or QTcF > 480 msec (using Fridericia’s correction); all as determined by screening ECG (mean of triplicate ECGs)
+Unstable cardiovascular function:\r\n* Symptomatic ischemia, or\r\n* Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on antiarrhythmic agents are excluded; 1st degree atrioventricular [AV] block or asymptomatic left anterior fascicular block/right bundle branch block [left anterior fascicular block (LAFB)/right bundle branch block (RBBB)] will not be excluded), or\r\n* Congestive heart failure (CHF) New York Heart Association (NYHA) class >= 3, or\r\n* Myocardial infarction (MI) within 3 months
+Clinically significant, uncontrolled heart disease and/ or a history of cardiac dysfunction including any of the following:\r\n* History of unstable angina pectoris, symptomatic pericarditis, myocardial infarction, coronary artery bypass grafting or coronary angioplasty within 12 months prior to study entry\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Patient has a left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* History of clinically significant ventricular arrhythmia and/or conduction delays within 12 months of screening\r\n* Systolic blood pressure > 160 mmHg or < 90 mmHg\r\n* Congenital long QT syndrome or family history of long QT syndrome\r\n* Bradycardia (heart rate < 50 at rest) by electrocardiogram (ECG) or pulse at screening.
+Cardiac function: ejection fraction (EF) >= 40%, no uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
+History or evidence of cardiovascular risk including any of the following:\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization\r\n* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Patients with intra-cardiac defibrillators
+Subject has active cardiac disease or a history of cardiac dysfunction including any of the following:\r\n* Unstable angina pectoris within 6 months prior to study entry\r\n* Symptomatic peritonitis\r\n* Documented myocardial infarction within 6 months prior to study entry\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Subject has a left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* Subject has any of the following cardiac conduction abnormalities\r\n* Ventricular arrhythmias except for benign premature ventricular contractions\r\n* Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medicine\r\n* Conduction abnormality requiring a pacemaker\r\n* Other cardiac arrhythmia not controlled with medication
+Significant cardiovascular disease, including:\r\n* Cardiac failure New York Heart Association (NYHA) class III or IV\r\n* Myocardial infarction, severe or unstable angina within 6 months prior to study day 1\r\n* History of serious arrhythmia (i.e., ventricular tachycardia, or ventricular fibrillation)\r\n* Cardiac arrhythmias requiring anti-arrhythmic medications
+Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
+Clinically significant cardiac disease or impaired cardiac function, such as:\r\n* Congestive heart failure (CHF) requiring treatment (New York Heart Association [NYHA] grade >= 2), left ventricular ejection fraction (LVEF) < 50% as determined by multi-gated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* History or current evidence of unstable, clinically significant cardiac arrhythmias or patients that require medications with a narrow therapeutic window, atrial fibrillation and/or conduction abnormality, e.g. congenital long QT syndrome, high-grade/complete atrioventricular (AV)-blockage\r\n* Acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft [CABG], coronary angioplasty, or stenting), < 3 months prior to screening
+Unstable angina or myocardial infarction within 6 months prior to randomization, New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, uncontrolled or persistent atrial fibrillation/flutter, history of ventricular fibrillation, ventricular tachycardia/torsade de pointes, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or grade 3 conduction system abnormalities unless subject has a pacemaker
+Presence of unstable atrial fibrillation (ventricular response > 100 beats per minute)
+Impaired cardiac function or clinically significant cardiac diseases, including any one of the following: \r\n* History or presence of sustained ventricular tachyarrhythmia; (patients with a history of atrial arrhythmia are eligible) \r\n* Any history of ventricular fibrillation or torsade de pointes \r\n* Bradycardia defined as heart rate (HR) < 50 beats per minute (bpm); patients with pacemakers are eligible if HR >= 50 bpm\r\n* Screening electrocardiogram (ECG) with a Fridericia's correction formula (QTcF) > 450 msec (QTcF = QT/^3 square root of RR); if potassium, magnesium, or calcium blood levels are below normal limits, consider repeating ECG after correction of these electrolytes\r\n* Right bundle branch block + left anterior hemiblock (bifascicular block) \r\n* Patients with myocardial infarction or unstable angina =< 6 months prior to starting study drug \r\n* Other clinically significant heart disease (e.g., congestive heart failure [CHF] New York [NY] Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
+History or evidence of cardiovascular risk including any of the following:\r\n* LVEF < lower limit of normal (LLN)\r\n* A QT interval corrected for heart rate using the Bazett’s formula QTcB >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to registration are eligible)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to registration\r\n* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Patients with intra-cardiac defibrillators\r\n* Known cardiac metastases
+Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, congenital long QT syndrome, or torsades de pointes)
+History or evidence of cardiovascular risk including any of the following:\r\n* Left ventricular ejection fraction (LVEF) < LLN\r\n* A QT interval corrected for heart rate using the Bazett’s formula Fridericia corrected QT interval (QTcB) >= 480 msec (>= 500 msec for subjects with bundle branch block)\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible)\r\n* Other clinically significant electrocardiogram (ECG) abnormalities including second (2nd) degree (type II) or third (3rd) degree atrioventricular (AV) block\r\n* Subject with intra-cardiac defibrillators or pacemakers\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization\r\n* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Known cardiac metastases
+History or evidence of cardiovascular risks including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within the past 24 weeks prior to randomization\r\n* History or evidence of current class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Intra-cardiac defibrillators\r\n* Abnormal cardiac valve morphology (>= grade 2) documented by ECHO; (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study\r\n* History or evidence of current clinically significant uncontrolled cardiac arrhythmias; clarification: subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible\r\n* Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy
+History or evidence of cardiovascular risks including any of the following:\r\n* QT interval corrected for heart rate using the Bazett’s formula QTcB >= 480 msec\r\n* History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within the past 24 weeks prior to randomization\r\n* History or evidence of current class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Intra-cardiac defibrillators\r\n* Abnormal cardiac valve morphology (>= grade 2) documented by ECHO; (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study\r\n* History or evidence of current clinically significant uncontrolled cardiac arrhythmias; clarification: subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible\r\n* Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy
+History or evidence of cardiovascular risk including any of the following:\r\n* LVEF < LLN\r\n* A QT interval corrected for heart rate using the Bazett’s formula (QTcB) >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to registration are eligible)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to registration\r\n* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Patients with intra-cardiac defibrillators or permanent pacemakers\r\n* Known cardiac metastases
+Class II or greater New York Heart Association Functional Classification criteria or serious cardiac arrhythmias likely to increase the risk of cardiac complications of cytokine therapy (e.g. ventricular tachycardia, frequent ventricular ectopy, or supraventricular tachyarrhythmia requiring chronic therapy)
+The following patients will be excluded from the high-dose aldesleukin arm (but may be eligible for cells alone arm):\r\n* History of coronary revascularization or ischemic symptoms\r\n* Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%; testing is required in patients with:\r\n** Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block\r\n** Age >= 60 years' old\r\n* Clinically significant patient history which in the judgment of the principal investigator would compromise the patient’s ability to tolerate aldesleukin
+Presence of any of the following on electrocardiogram (ECG):\r\n* Atrial arrhythmias, including atrial fibrillation and flutter\r\n* Atrioventricular (AV) block\r\n* Heart rate < 60 beats/minute unless the participant is otherwise eligible, without significant cardiac concerns and approval is obtained by the protocol chair/study cardiologist prior to enrollment\r\n* Heart rate > 100 beats/minute\r\n* Ventricular fibrillation\r\n* Ventricular tachycardia\r\n* Premature ventricular contractions\r\n* Wolff-Parkinson-White syndrome\r\n* NOTE: any questions on cardiac eligibility should be reviewed by the Study Cardiologist for approval in advance of enrollment
+Patients may not have any clinically significant cardiovascular disease including the following:\r\n* Myocardial infarction or ventricular tachyarrhythmia within 6 months\r\n* Prolonged corrected QT (QTc) > 480 msec (Fridericia correction)\r\n* Known ejection faction less than institutional normal\r\n* Major conduction abnormality (unless a cardiac pacemaker is present)
+Patients with uncontrolled angina, severe uncontrolled ventricular arrhythmias, or\n             electrocardiographic evidence of acute ischemia or active conduction system\n             abnormalities will be excluded
+History of any of the following cardiovascular events or conditions within the past 6\n             months prior to enrolment: myocardial infarction, unstable angina, cerebrovascular\n             accident or transient ischemic attack, New York Heart Association Class ? II chronic\n             heart failure, hypokalemia, significant arrhythmia*; QTc interval >430 msec or use of\n             drugs that prolong the QT interval at screening; family history of long QT\n             syndrome.(* Significant arrhythmias are defined as symptoms of syncope or severe\n             palpitations (palpitations requiring referral to cardiac monitoring), or ECG findings\n             of supraventricular tachycardia (including ventricular fibrillation) or ventricular\n             ectopy (ventricular premature depolarization).
+Patient must not have any history or evidence of cardiovascular risk including any of the following:\r\n* QT interval corrected by Bazett's formula (QTcB) >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: subjects with controlled atrial fibrillation for > 30 days prior to registration are eligible)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to registration\r\n* History or evidence of current >= class II congestive heart failure as defined by New York Heart Association\r\n* Abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study\r\n* Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Intra-cardiac defibrillator or permanent pacemaker\r\n* Cardiac metastases
+Clinically significant cardiac pathology: myocardial infarction within 6 months prior to enrollment, class III or IV heart failure according to New York Heart Association (NYHA), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or acute conduction system abnormalities; specifically, any history of cardio-vascular pathology or symptoms, not clearly fitting this exclusion criterion will prompt an evaluation by a Clinical Center Cardiologist and eligibility will be considered on a case-by-case basis; should the cardiologist deem the patient’s findings on work-up to be not clinically significant pathology, the patient will have met this exclusion criterion
+Patient has active cardiac disease including any of the following: \r\n* Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) \r\n* Corrected QT (QTc) > 480 msec on screening electrocardiogram (ECG) (using the Fridericia QT correction [QTcF] formula)\r\n* Angina pectoris that requires the use of anti-anginal medication\r\n* Ventricular arrhythmias except for benign premature ventricular contractions\r\n* Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication\r\n* Conduction abnormality requiring a pacemaker\r\n* Valvular disease with document compromise in cardiac function \r\n* Symptomatic pericarditis
+Clinically significant cardiac pathology: myocardial infarction within 6 months prior to enrollment, class III or IV heart failure according to New York Heart Association (NYHA), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
+Myocardial infarction (MI) within 6 months prior to study entry, New York Heart Association (NYHA) class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities
+Patient must not have ongoing ventricular cardiac dysrhythmias of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4 grade > 2; patients with a history of serious ventricular arrhythmia (ventricular tachycardia [VT] or ventricular fibrillation [VF] > 3 beats in a row) are also excluded; additionally, patients with ongoing atrial fibrillation are not eligible
+Cardiovascular criteria will exclude a patient from participation in the study will include:\r\n* Screening electrocardiogram (ECG) with a QTc > 450 msec;\r\n* Patients with congenital long QT syndrome; \r\n* History or presence of sustained ventricular tachycardia;\r\n* Any history of ventricular fibrillation or torsades de pointes;\r\n* Bradycardia defined as heart rate (HR) < 50 bpm;\r\n* Right bundle branch block + left anterior hemiblock (bifascicular block);\r\n* Patients with myocardial infarction or unstable angina < 6 months prior to starting study drug;\r\n* Congestive heart failure (CHF) New York (NY) Heart Association class III or IV;\r\n* Patients with an ejection fraction =< 45% assessed by multi gated acquisition scan (MUGA) or echocardiogram (ECHO) scan within 14 days of day 1\r\n* Poorly controlled hypertension
+Patient had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
+Participant with clinical signs of heart or coronary failure, or evidence of left ventricular ejection fraction (LVEF) < 40%; participant with myocardial infarction within 6 months prior to enrollment or have New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conductive system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
+Subject with clinically significant cardiac arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes, second degree or third degree atrioventricular heart block without a permanent pacemaker in place)
+Subjects with a known history of severe and/or uncontrolled ventricular arrhythmias.
+Clinically significant cardiovascular disease (that is, active or <3 months prior to enrollment): cerebral vascular accident/stroke, myocardial infarction, unstable angina, congestive heart failure (New York Heart Association Classification Class ? II), second-degree or third-degree AV block (unless paced) or any AV block with PR >220 msec. Ongoing cardiac dysrhythmias of NCI CTCAE Grade ?2, uncontrolled atrial fibrillation of any grade, bradycardia defined as <50 bpm (unless patient is otherwise healthy such as long-distance runners, etc.), machine-read ECG with QTc >470 msec, or congenital long QT syndrome.
+Participant who had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
+Patients with clinically significant cardiovascular disease; this includes:\r\n* Uncontrolled hypertension, defined as systolic greater than 150 mmHg or diastolic greater than 90 mmHg\r\n* Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry\r\n* Congenital long QT syndrome or baseline QTc greater than 480 milliseconds\r\n* Myocardial infarction or unstable angina within 6 months prior to registration\r\n* New York Heart Association (NYHA) class III or greater congestive heart failure\r\n* History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or serious cardiac arrhythmia requiring medication; this does not include asymptomatic, atrial fibrillation with controlled ventricular rate\r\n* Patients who have received prior treatment with an anthracycline (including doxorubicin, excluding liposomal doxorubicin) must have an echocardiogram or multigated acquisition scan (MUGA) assessment and are excluded if they have an ejection fraction less than 50%\r\n* CTCAE v.4.0 grade 2 or greater peripheral vascular disease (at least brief less than 24 hours [hrs]) episodes of ischemia managed non-surgically and without permanent deficit\r\n* History of cardiac angioplasty or stenting within 6 months prior to registration; history of coronary artery bypass graft surgery within 6 months prior to registration\r\n* Arterial thrombosis within 6 months prior to registration
+history within the last 12 months of any of the following conditions: syncope of cardiovascular etiology, ventricular tachycardia, ventricular fibrillation, or sudden cardiac arrest
+Patients with a known history of severe and/or uncontrolled ventricular arrhythmias
+Clinically significant cardiac disease or impaired cardiac function, such as:\r\n* Baseline left ventricular ejection fraction (LVEF) < 50% on baseline echocardiogram or multi gated acquisition scan (MUGA)\r\n* Congestive heart failure requiring treatment (e.g., New York Heart Association class II, III or IV) within 6 months prior to screening\r\n* Acute coronary syndromes < 3 months prior to screening (including myocardial infarction, unstable angina, coronary artery bypass graft, coronary angioplasty, or stenting)\r\n* Uncontrolled arterial hypertension defined by blood pressure > 140/100 mm Hg at rest (average of 3 consecutive readings)\r\n* History or current evidence of unstable, clinically significant cardiac arrhythmias\r\n* Patients that require medications with a narrow therapeutic window\r\n* Clinically significant conduction abnormality, e.g. congenital long QT syndrome, high-grade/complete atrioventricular (AV)-blockage\r\n* Corrected QT interval (QTc) > 480 msec on screening electrocardiogram (ECG)
+CLINICAL/LABORATORY CRITERIA: Patients must have corrected QT (QTc) interval =< 480 msec (using the Bazett’s formula) on electrocardiogram (ECG) performed within 42 days prior to registration; history or evidence of current clinically significant uncontrolled arrhythmias are not eligible; however, patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible; patients must not have atrial fibrillation > grade 2 on the screening ECG; patients with CTCAE grade 1-2 atrial fibrillation on their screening ECG must have a second ECG performed prior to registration and more than 30 days from the screening ECG (either before or after) with the most recent ECG showing stable or improving grade of atrial fibrillation
+Significant medical comorbidities, including uncontrolled hypertension (diastolic blood pressure >115 mm Hg), unstable angina, congestive heart failure (greater than New York Heart Association class II), severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia, poorly controlled diabetes, severe chronic pulmonary disease, coronary angioplasty, myocardial infarction within 6 months prior to Screening, or uncontrolled atrial or ventricular cardiac arrhythmias.
+History or presence of complete left bundle branch block, heart block, cardiac pacemaker or significant arrhythmia.
+Personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy.
+Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiography (ECG) (e.g., complete left bundle branch block, third degree heart block, second degree heart block)
+Subject has active cardiac disease or a history of cardiac dysfunction including any of the following:\r\n* Congenital long QT syndrome\r\n* Corrected QT (QTc) interval >= 500 ms on the screening electrocardiogram (ECG) (using the corrected QT Fridericia [QTcF] formula)\r\n* Myocardial infarction within 6 months of course 1 day 1 (C1D1); subjects with a history of myocardial infarction between 6 and 12 months prior to C1D1 who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event may participate\r\n* Other significant ECG abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min)\r\n* Symptomatic coronary artery disease (CAD), e.g., angina Canadian class II-IV; in any subject in whom there is doubt, the subject should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present\r\n* An ECG recorded at screening showing evidence of cardiac ischemia (ST depression of >= 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the subject should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present\r\n* Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II to IV definitions and/or ejection fraction < 40% by multi gated acquisition (MUGA) scan or < 50% by echocardiogram and/or magnetic resonance imaging (MRI)\r\n* A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), torsade de pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD)\r\n* Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes\r\n* Uncontrolled hypertension, i.e., blood pressure (BP) of >= 160/95; subjects who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria\r\n* Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)\r\n* Subjects taking drugs leading to significant QT prolongation\r\n* Concomitant use of cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors
+Active congestive heart failure or ventricular arrhythmia requiring medication
+Uncontrolled or clinically significant conduction abnormalities (e.g., ventricular tachycardia on antiarrhythmics are excluded, 1st degree AV block or asymptomatic LAFB/RBBB are eligible)
+Patients with a history or evidence of cardiovascular risk, including any of the following:\r\n* Left ventricular ejection fraction (LVEF) < lower limit of normal (LLN)\r\n* Bazett's corrected QT (QTcB) >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias\r\n* Exception: Subjects with controlled atrial fibrillation for > 30 days prior to randomization are eligible\r\n* History of (within 6 months prior to randomization) acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting\r\n* History or evidence of current >= class II congestive heart failure as defined by New York Heart Association (NYHA)\r\n* Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Patients with intra-cardiac defibrillators or permanent pacemakers\r\n* Known cardiac metastases
+History of torsades de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia (< 50 bpm), heart block (excluding first degree block, being PR interval only), or congenital long QT syndrome. Patients with a history of atrial arrhythmias should be discussed with the Medical Monitor.
+Had a myocardial infarct within 6 months before enrollment, New York Heart Association (NYHA) Class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities
+Have a personal history of any of the following conditions: syncope of either unexplained or cardiovascular etiology, ventricular arrhythmia (including but not limited to ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest. Exception: Participants with controlled atrial fibrillation for >30 days prior to study treatment initiation are eligible.
+Clinically significant, uncontrolled heart disease or cardiac repolarization abnormalities and/or recent events including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening\r\n* Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g. bifascicular block, Mobitz type II and third-degree AV block) long QT syndrome or family history of long QT syndrome\r\n* Idiopathic sudden death or congenital long QT syndrome\r\n* Risk factors for torsades de pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia\r\n* Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause torsades de pointe that cannot be discontinued (within 5 half-lives or 7 days prior to starting study drug) or replaced by safe alternative medication\r\n* Inability to determine the QT interval on screening (corrected QT interval [QTcF], using Fridericia’s correction)\r\n* Systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg at screening\r\n* Bradycardia (heart rate < 50 at rest), by electrocardiogram (ECG) or pulse, at screening\r\n* Tachycardia (heart rate > 110 at rest), by ECG or pulse at screening
+History of torsades de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia (< 50 bpm), heart block (excluding first degree block, being PR interval only), or congenital long QT syndrome. Subjects with a history of atrial arrhythmias should be discussed with the medical monitor
+Patients who have class III or IV heart failure (as defined by the New York Heart Association), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities are not eligible
+Absence of history of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
+Cardiac abnormalities as evidenced by any of the following: History or current \untreated\ clinically significant uncontrolled arrhythmias; Clinically significant conduction abnormalities or arrhythmias, subjects with Bundle Branch Block; Presence of cardiac pacemaker; History or evidence of current >=Class II congestive heart failure as defined by New York Heart Association (NYHA); History of acute coronary syndromes (including unstable angina and myocardial infarction ), coronary angioplasty, or stenting within the past 3 months.
+Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
+Significant medical comorbidities, including uncontrolled hypertension (diastolic blood pressure greater than 115 mm Hg), unstable angina, congestive heart failure (greater than New York Heart Association class II), severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia, poorly controlled diabetes, severe chronic pulmonary disease, coronary angioplasty, or myocardial infarction within 6 months prior to screening, or uncontrolled atrial or ventricular cardiac arrhythmias.
+Significant cardiovascular disease, including: Active clinically symptomatic left ventricular failure,uncontrolled hypertension, myocardial infarction, severe angina, or unstable angina within 6 months prior to administration of first dose of study drug, history of serious ventricular arrhythmia, cardiac arrhythmias requiring anti-arrhythmic medications.
+Abnormal 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 a. Patients with evidence of prior infarction who are New York Heart Association (NYHA) functional class II, III, or IV are excluded, as are patients with marked arrhythmia such as Wolff Parkinson White pattern or complete atrioventricular (AV) dissociation
+Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, known serious cardiac illness or psychiatric illness/social situations that would limit compliance with study requirements; known serious cardiac illness or medical conditions include, but are not limited to:\r\n* History of documented congestive heart failure (CHF), New York Heart Association (NYHA) class II/III/IV, with a history of dyspnea, orthopnea, or edema that requires current treatment with angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, beta blockers, or diuretics\r\n** NOTE: use of these medications for the treatment of hypertension is allowed\r\n* Screening QTc (QT interval corrected for heart rate) > 470 msec or history of QT (cardiac interval from start of Q wave to end of T wave) prolongation while taking other medications\r\n* High-risk uncontrolled arrhythmias (ventricular arrhythmias, high-grade atrioventricular [AV]-block, supra-ventricular arrhythmias that are not adequately rate-controlled)\r\n* Arrhythmias that require current treatment with the following anti-arrhythmic drugs: flecainide, moricizine, or propafenone\r\n* Current coronary artery disease with a history of myocardial infarction, angioplasty, or coronary bypass surgery within the preceding 6 months, or angina pectoris that has been symptomatic within the preceding 6 months
+Subject has history (within previous 5 years) of clinically significant pulmonary hypertension, uncontrolled systemic hypertension, hypertensive crisis, congestive heart failure, myocardial infarction, aneurysm or aneurysm repair or the left ventricular ejection fraction (LVEF) less than or equal to 50%.
+Persistent or uncontrolled ventricular arrhythmias or atrial fibrillation.
+Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiographic (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
+Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular (AV) block, type II AV block, or 3rd degree block
+Requirement for inotropic support (excluding digoxin), or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation, or ventricular tachycardia);
+History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening
+Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
+Patient has impaired cardiac function including any of the following: \r\n* Presence or history of pericardial effusion and/or pericarditis\r\n* Acute myocardial infarction, symptomatic angina pectoris =< 6 months prior to starting study drug \r\n* Presence of congestive heart failure >= New York Heart Association (NYHA) class 3\r\n* Corrected QT interval (QTc) > 480 ms on a screening electrocardiogram (ECG) \r\n* Screening left ventricular ejection fraction (LVEF) < 45% by echocardiography or multi gated acquisition scan (MUGA) \r\n* Uncontrolled cardiac arrhythmia including uncontrolled atrial fibrillation/atrial flutter/sinus tachycardia, complete left bundle branch block, congenital long QT syndrome\r\n* Presence of permanent cardiac pacemaker \r\n* Other clinically significant heart disease
+Patients have clinically significant cardiovascular disease, including any of the following \r\n* Any history of acute coronary syndrome including myocardial infarction, stable or unstable angina, coronary artery bypass grafting (CABG), coronary angioplasty or stenting, or known obstructive coronary artery disease\r\n* Symptomatic chronic heart failure (New York Heart Association criteria, class II-IV) \r\n* Evidence of clinically significant cardiac arrhythmias and/or conduction abnormalities < 6 months prior to screening except atrial fibrillation (AF) and paroxysmal supraventricular tachycardia (PSVT)
+History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or serious cardiac arrhythmia requiring medication. This does not include asymptomatic atrial fibrillation with controlled ventricular rate.
+Patients 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.
+Have a personal history of any of the following conditions: presyncope or syncope of either unexplained or cardiovascular etiology, ventricular arrhythmia (including but not limited to ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
+Presence of poorly controlled atrial fibrillation (ventricular heart rate > 100 beats per minute [bpm])
+Have a personal history of any of the following conditions: presyncope or syncope of either unexplained or cardiovascular etiology, ventricular arrhythmia (including but not limited to ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest. Exception: Participants with controlled atrial fibrillation for >30 days prior to study treatment are eligible.
+Since IL-2 is administered following cell infusion:\r\n* Patients will be excluded if they have a history of clinically significant electrocardiogram (ECG) abnormalities, symptoms of cardiac ischemia or arrhythmias and have a left ventricular ejection fraction (LVEF) < 45% on a cardiac stress test (stress thallium, stress multi gated acquisition [MUGA] scan, dobutamine echocardiogram, or other stress test)\r\n* Similarly, patients who are 50 years old with a baseline LVEF < 45% will be excluded\r\n* Patients with ECG results of any conduction delays (PR interval > 200 ms, corrected QT interval [QTC] > 480 ms), sinus bradycardia (resting heart rate < 50 beats per minute), sinus tachycardia (heart rate > 120 beats per minute) will be evaluated by a cardiologist prior to starting the trial; patients with any arrhythmias, including atrial fibrillation/atrial flutter, excessive ectopy (defined as > 20 premature ventricular contractions [PVCs] per minute), ventricular tachycardia, 3rd degree heart block will be excluded from the study unless cleared by a cardiologist\r\n* Patients with pulmonary function test abnormalities as evidenced by a forced expiratory volume of the lung in 1 second (FEV1)/forced vital capacity (FVC) < 70% of predicted for normality will be excluded
+History or evidence of cardiac risk, including:\r\n* Corrected QT interval on screening electrocardiogram (ECG) > 470 msec\r\n* Left ventricular ejection fraction (LVEF) < 50%\r\n* Clinically significant uncontrolled arrhythmias or arrhythmia requiring treatment with the exceptions of atrial fibrillation and paroxysmal supraventricular tachycardia\r\n* History of acute coronary syndromes within 6 months prior to the first dose of study therapy (including myocardial infarction and unstable angina, coronary artery bypass graft, angioplasty, or stenting)
+Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:\r\n* Myocardial infarction within the past 6 months\r\n* Uncontrolled angina within the past 6 months\r\n* Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation or Torsades de pointes); controlled atrial fibrillation by itself is not an exclusion criterion\r\n* Baseline corrected QT (QTc) interval greater than 500 milliseconds
+Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
+Patient had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
+ENTRY CRITERIA:\n\n        DISEASE CHARATERISTICS:\n\n          -  Histologically confirmed high-risk (high grade Ta, T1 or carcinoma in situ, tumor >4\n             cm or multi-focal) transitional cell carcinoma s/p TURBT with no remaining resectable\n             disease within 4 weeks of study entry\n\n          -  Intolerant of treatment with BCG or failure (refractory or relapsing) of at least one\n             prior treatment with BCG\n\n          -  Refuse or intolerant of a radical cystectomy\n\n          -  No Evidence of regional and/or distant metastasis\n\n        PRIOR/CONCURRENT THERAPY:\n\n          -  No concurrent radiotherapy, other chemotherapy, or other immunotherapy\n\n          -  No scheduled radiotherapy, chemotherapy, other immunotherapy, or surgery before the\n             scheduled response evaluation\n\n          -  Must have recovered from side effects of prior treatments\n\n          -  No concurrent use of other investigational agents\n\n        PATIENT CHARACTERISTICS:\n\n        Age\n\n        • ? 18 years\n\n        Performance Status\n\n        • ECOG 0, 1, or 2\n\n        Bone Marrow Reserve\n\n          -  Absolute neutrophil count (AGC/ANC) ? 1,000/uL\n\n          -  Platelets ? 100,000/uL\n\n          -  Hemoglobin ? 8 g/dL\n\n        Renal Function\n\n        • Glomerular Filtration Rate (GFR) ? 50mL/min\n\n        Hepatic Function\n\n          -  Total bilirubin ? 2.0 X ULN\n\n          -  AST, ALT, ALP ? 3.0 X ULN\n\n        Cardiovascular\n\n          -  No congestive heart failure < 6 months\n\n          -  No severe/unstable angina pectoris < 6 months\n\n          -  No myocardial infarction < 6 months\n\n          -  No history of ventricular arrhythmias\n\n          -  No NYHA Class > II CHF\n\n          -  No uncontrollable supraventricular arrhythmias\n\n          -  No history of a ventricular arrhythmia\n\n          -  No other clinical signs of severe cardiac dysfunction\n\n          -  Normal Transthoracic Echocardiogram (TTE) is required for patients who have history of\n             EKG abnormalities, CHF, coronary artery disease or other cardiac disease, or have\n             history of having received adriamycin or doxorubicin\n\n          -  No patients with a left ventricular ejection fraction (LVEF) of less than 50%\n\n        Pulmonary\n\n        • Normal clinical assessment of pulmonary function\n\n        Other\n\n          -  Negative serum pregnancy test if female and of childbearing potential\n\n          -  Women who are not pregnant or nursing\n\n          -  Subjects, both females and males, with reproductive potential must agree to use\n             effective contraceptive measures for the duration of the study\n\n          -  No known autoimmune disease other than corrected hypothyroidism\n\n          -  No known prior organ allograft or allogeneic transplantation\n\n          -  Not HIV positive\n\n          -  No active systemic infection requiring parenteral antibiotic therapy\n\n          -  No ongoing systemic steroid therapy required\n\n          -  No history or evidence of uncontrollable CNS disease\n\n          -  No psychiatric illness/social situation\n\n          -  No other illness that in the opinion of the investigator would exclude the subject\n             from participating in the study\n\n          -  Must provide informed consent and HIPAA authorization and agree to comply with all\n             protocol-specified procedures and follow-up evaluations
+Impaired cardiac function:\r\n* Corrected QT interval (QTc) > 480 on screening electrocardiogram (ECG)\r\n* Previous history of angina pectoris or acute myocardial infarction (MI) within 6 months\r\n* Congestive heart failure (New York Heart Association functional classification III-IV) or baseline multigated acquisition scan (MUGA)/echocardiogram (ECHO) shows estimated left ventricular ejection fraction (LVEF) < 45%\r\n* Any history of torsade de pointes, ventricular fibrillation, uncontrolled ventricular tachycardia, or uncontrolled atrial fibrillation
+Patients with history of myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
+Since interleukin (IL)-2 is administered following cell infusion: \r\n* Patients will be excluded if they have a history of clinically significant electrocardiogram (ECG) abnormalities, symptoms of cardiac ischemia or arrhythmias and have a left ventricular ejection fraction (LVEF) < 45% on a cardiac stress test (stress thallium, stress multigated acquisition [MUGA], dobutamine echocardiogram, or other stress test) \r\n* Similarly, patients who are 50 years old with a baseline LVEF < 45% will be excluded\r\n* Patients with ECG results of any conduction delays (PR interval > 200 ms, corrected QT interval [QTC] > 480 ms), sinus bradycardia (resting heart rate < 50 beats per minute), sinus tachycardia (heart rate [HR] > 120 beats per minute) will be evaluated by a cardiologist prior to starting the trial; patients with any arrhythmias, including atrial fibrillation/atrial flutter, excessive ectopy (defined as > 20 premature ventricular contractions [PVCs] per minute), ventricular tachycardia, 3rd degree heart block will be excluded from the study unless cleared by a cardiologist\r\n* Patients with pulmonary function test abnormalities as evidenced by a forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) < 70% of predicted for normality will be excluded
+New York Heart Association (NYHA) classification III or IV, known symptomatic coronary artery disease, or symptoms of coronory artery disease on systems review, or known cardiac arrhythmias (atrial fibrillation or supraventricular tachycardia [SVT])
+Clinically significant, uncontrolled heart disease and/or recent events including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 12 months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Patient has a left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening\r\n* History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening\r\n* Congenital long QT syndrome or family history of long QT syndrome\r\n* Bradycardia (heart rate <50 at rest), by electrocardiography (ECG) or pulse, at screening\r\n* Systolic blood pressure (SBP) >160 mmHg or <90 mmHg at screening
+Impaired cardiac function or clinically significant cardiac diseases, history of arrhythmia (including ventricular fibrillation or torsade de pointes), bradycardia < 50 beats per minute (bpm), screening electrocardiogram (ECG) with prolonged corrected QT (QTc) (> 450 msec), uncontrolled hypertension or any history or presence of sustained ventricular tachyarrhythmia
+Have clinically significant cardiac disease (NYHA Class III or IV); clinically significant arrhythmia i.e. ventricular tachycardia, ventricular fibrillation, or \Torsade de Pointes\. Myocardial infarction with uncontrolled angina within 6 months, congestive heart failure, or clinical significant cardiomyopathy
+Medically documented cardiac syncope, uncompensated congestive heart failure, myocardial infarction within the previous 6 months, unstable angina pectoris, clinically significant repetitive atrial or ventricular arrhythmias despite antiarrhythmic treatment, or severe orthostatic hypotension or clinically significant uncompensated autonomic insufficiency
+Patients have clinically significant cardiovascular disease, including any of the following:\r\n* History of acute coronary syndrome including myocardial infarction, unstable angina, coronary artery bypass surgery (CABG), coronary angioplasty or stenting < 6 months prior to screening\r\n* Symptomatic chronic heart failure (New York Heart Association Criteria, class II-IV)\r\n* Evidence of clinically significant cardiac arrhythmias and/or conduction abnormalities < 6 months prior to screening except atrial fibrillation (AF) and paroxysmal supraventricular tachycardia (PSVT)
+Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities, including any of the following: a. History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to screening. b. History of documented congestive heart failure (New York Heart Association functional classification III-IV). c. Documented cardiomyopathy. d. Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening. e. Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block). Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: a. Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia. b. Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued (within 5 half-lives or 7 days prior to starting study drug) or replaced by safe alternative medication. c. Inability to determine the QT interval on screening (QTcF, using Fridericia’s correction). d. Systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg at screening.
+Known congestive heart failure, significant ventricular arrhythmias, cirrhosis, grade 4/5 chronic kidney disease, uncontrolled diabetes
+Patients with any of the following cardiovascular diseases are excluded:\r\n* History of myocardial infarction within six months\r\n* Unstable angina\r\n* Angina pectoris that requires the use of anti-anginal medication\r\n* History of documented congestive heart failure (New York Heart Association [NYHA] classification of III or IV) or documented cardiomyopathy\r\n* Valvular disease with documented compromise in cardiac function\r\n* If cardiac function assessment is clinically indicated or performed: left ventricular ejection fraction (LVEF) less than normal per institutional guidelines, or < 55%, if threshold for normal not otherwise specified by institutional guidelines; patients with the following risk factor should have a baseline cardiac function assessment:\r\n** Prior treatment with anthracyclines\r\n* Any prior history of hypertensive crisis or hypertensive encephalopathy\r\n* Patients may not have any evidence of pre-existing inadequately controlled hypertension (defined as a systolic blood pressure [BP] of > 140 mmHg or a diastolic BP of > 90 mmHg), and must have a normal blood pressure (=< 140/90 mmHg) taken in the clinic setting by a medical professional within 2 weeks prior to starting study\r\n* Clinically significant peripheral vascular disease\r\n* Vascular disease including aortic aneurysm or dissection\r\n* History of stroke, transient ischemic attack or subarachnoid hemorrhage\r\n* Ventricular arrhythmias except for benign premature ventricular contractions\r\n* Cardiac conduction abnormality requiring a pacemaker\r\n* Known history of QT/corrected QT interval (QTc) prolongation or torsades de pointes\r\n* QTc prolongation > 470 msec or other significant electrocardiogram (ECG) abnormality noted during screening
+Patients who have experienced any of the following procedures or conditions currently or in the preceding 12 months:\r\n* Coronary artery bypass graft\r\n* Angioplasty\r\n* Vascular stent\r\n* Myocardial infarction\r\n* Angina pectoris\r\n* Congestive heart failure New York Heart Association grade >= 2 (ventricular arrhythmias requiring continuous therapy)\r\n* Supraventricular arrhythmias including atrial fibrillation, which are uncontrolled\r\n* Hemorrhagic or thrombotic stroke, including transient ischemic attacks or any other central nervous system bleeding\r\n* History of drug abuse or alcohol abuse, as judged by the investigator
+Patients who have any serious or uncontrolled medical disorder that would impair the ability of the subject to receive protocol therapy are not eligible; these include, but are not limited to: \r\n* Active infection that is not well controlled\r\n* Known pleural or pericardial effusion at baseline \r\n* Clinically significant gastrointestinal disease or digestive dysfunction compromising absorption of dasatinib\r\n* Pulmonary arterial hypertension \r\n* Uncontrolled or significant cardiovascular disease, including:\r\n** Myocardial infarction within 6 months of enrollment date\r\n** Uncontrolled angina or congestive heart failure within 3 months of enrollment date\r\n** Left ventricular ejection fraction (LVEF) < 40%\r\n** Significant cardiac conduction abnormality, including: \r\n*** History of clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes)\r\n*** History of second or third degree heart block (except for second degree type 1)\r\n*** Corrected QT (QTc) interval > 500 msec, unless a cardiac pacemaker is present\r\n* Prior malignancy active within the previous 3 years, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancers, superficial bladder cancer, or carcinoma in situ of the prostate, cervix or breast\r\n* Subjects with active, known or suspected autoimmune disease; (Note: Subjects with vitiligo, type I diabetes mellitus, hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll)\r\n* Psychiatric illness/social situations that would limit compliance with study requirements\r\n* Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient’s safety or study endpoints
+Patients who currently have or have a history of the following within 6 months preceding study entry are not eligible: unstable angina (UA) or myocardial infarction (MI), clinically significant atrial or ventricular arrhythmias (e.g., atrial fibrillation [AF], atrial flutter, ventricular tachycardia, ventricular fibrillation, or torsades de pointes), New York Heart Association (NYHA) class III or IV heart failure
+Have a personal history of any of the following conditions: syncope of either unexplained or cardiovascular etiology, ventricular tachycardia, ventricular fibrillation, or sudden cardiac arrest.
+History of congestive heart failure or other findings of ventricular dysfunction
+Cardiac abnormalities as evidenced by any of the following: History of or current \untreated\ clinically significant uncontrolled arrhythmias, Clinically significant conduction abnormalities or arrhythmias, Presence of cardiac pacemaker, History or evidence of current >=Class II congestive heart failure as defined by New York Heart Association (NYHA), History of acute coronary syndromes (including unstable angina and myocardial infarction), coronary angioplasty, or stenting within the past 3 months. Subjects with a history of stent placement requiring ongoing antithrombotic therapy (e.g., clopidogrel, prasugrel) will not be permitted to enroll.
+have documented major electrocardiogram (ECG) abnormalities (not responding to medical treatments) at the investigator's discretion (for example, symptomatic or sustained atrial or ventricular arrhythmias, second- or third-degree atrio ventricular block, complete bundle branch block, ventricular hypertrophy, or recent myocardial infarction).
+Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular (AV) block, type II AV block, or 3rd degree block
+History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, Torsade de Pointes).
+History of any of the following within the last 6 months prior to study entry:\r\n*Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures\r\n* Ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures\r\n* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)\r\n* Placement of a pacemaker for control of rhythm\r\n* New York Heart Association (NYHA) class III or IV heart failure \r\n* Pulmonary embolism
+Documented unstable angina or myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or grade 3 conduction system abnormalities (unless subject has a pacemaker), left ventricular ejection fraction (LVEF) < 40%, history of torsade de pointe
+Unstable cardiovascular function:\r\n* Symptomatic ischemia, or \r\n* Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on antiarrhythmic agents are excluded; 1st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block/right bundle branch block (LAFB/RBBB) will not be excluded), or\r\n* Congestive heart failure (CHF) NYHA class >= 3, or\r\n* Myocardial infarction (MI) within 3 months
+Myocardial infarction within 6 months prior to enrollment or New York Hospital Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled arrhythmias, or electrocardiographic evidence of acute ischemia or significant conduction system abnormalities in the opinion of the Investigator. Prior to study entry any known abnormality on an electrocardiogram (ECG) must be determined and documented by the Investigator to be not clinically significant to the patient participation in this study.
+The participant has symptomatic congestive heart failure (CHF), left ventricular dysfunction (LVEF < 50%), severe myocardial insufficiency, cardiac arrhythmia, or cardiomyopathy.
+Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
+History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or cardiac arrhythmias requiring anti-arrhythmic medications, except for atrial fibrillation that is well controlled with anti-arrhythmic medication.
+Any of the following within 6 months before the first dose of study treatment:\r\n* Unstable angina pectoris\r\n* Clinically-significant cardiac arrhythmias\r\n* Stroke (including transient ischemic attack [TIA], or other ischemic event)\r\n* Myocardial infarction\r\n* Thromboembolic event requiring therapeutic anticoagulation (Note: subjects with a venous filter [e.g. vena cava filter] are not eligible for this study)\r\n* Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes)\r\n* Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec), may use either the Fridericia and Bazett’s correction\r\n* Hypokalemia or hypomagnesemia that is not corrected prior to dasatinib administration\r\n* Patients should not be taking drugs that are generally accepted to have a risk of causing torsades de pointes; the following must be discontinued at least 7 days prior to starting dasatinib to be eligible: quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, erythromycins, clarithromycin, chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine
+Patients with New York Heart Association (NYHA) class III and IV heart failure, myocardial infarction in the preceding 6 months, and significant conduction abnormalities, including but not limited to second (2nd) degree atrioventricular (AV) block type II, third (3rd) degree block, QT prolongation (corrected QT [QTc] > 500 msec), sick sinus syndrome, ventricular tachycardia, symptomatic bradycardia (heart rate < 50 beats per minute [bpm]), hypotension, light headedness and syncope; patients with active atrial fibrillation will be excluded; the protocol excludes patients who have within the past year had a stent and by recommendation of their cardiologist need to stay on anticoagulants such as warfarin equivalent vitamin K antagonist
+Impaired cardiac function or clinically significant cardiac diseases, including any of the following: a) history of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis less than 12 months prior to screening b) history of documented congestive heart failure (New York Heart Association functional classification III-IV) c) documented cardiomyopathy d) patient has a left ventricular ejection fraction (LVEF) less than 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening e) history of ventricular, supraventricular, nodal arrhythmias, or any other cardiac arrhythmias, long QT syndrome or conduction abnormality within 12 months prior to starting study drug f) congenital long QT syndrome or a family history of corrected QT interval (QTc) prolongation g) on screening, inability to determine the corrected QT for Fridericia (QTcF) interval on the electrocardiogram (ECG) (i.e.: unreadable or not interpretable) or QTcF > 450 msec (using Fridericia’s correction); all as determined by screening ECG (mean of triplicate ECGs)
+Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g., complete left bundle branch block, third degree heart block
+Unstable cardiovascular function:\r\n* Symptomatic ischemia, or\r\n* Uncontrolled clinically significant conduction abnormalities (i.e. ventricular tachycardia on antiarrhythmics are excluded and 1st degree atrioventricular [AV] block or asymptomatic left anterior fascicular block [LAFB]/right bundle branch block [RBBB] will not be excluded), or\r\n* Congestive heart failure (CHF) of New York Heart Association (NYHA) class >= 3, or\r\n* Myocardial infarction (MI) within 3 months
+Significant cardiac disease or risk factors as indicated by MUGA or echocardiogram performed =< 60 days prior to registration and/or by presence of any of the following:\r\n* History of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (version 4.0) grade >= 3 symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) criteria class >= II\r\n* Angina pectoris requiring anti-anginal medication, serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality, or clinically significant valvular disease\r\n* High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart rate > 100/min at rest, significant ventricular arrhythmia [ventricular tachycardia], or higher-grade atrioventricular [AV]-block [second degree AV-block Type 2 [Mobitz 2] or third degree AV-block])\r\n* Significant symptoms (grade >= 2) relating to left ventricular dysfunction, cardiac arrhythmia, or cardiac ischemia\r\n* Myocardial infarction within 12 months prior to randomization\r\n* Uncontrolled hypertension (systolic blood pressure > 180 mmHg and/or diastolic blood pressure >100 mmHg)\r\n* Evidence of transmural infarction on electrocardiogram (ECG)\r\n* Requirement for oxygen therapy
+Major cardiac-related diseases, medications, or laboratory abnormalities including the following: a) clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or indwelling temporary pacemaker, b) ventricular tachycardia or a supraventricular tachycardia that requires treatment with a class Ia antiarrhythmic drug (eg, quinidine, procainamide, disopyramide) or class III antiarrhythmic drug (eg, sotalol, amiodarone, dofetilide); use of other antiarrhythmic drugs is permitted; c) use of medications that have been linked to the occurrence of torsades de pointes, d) second- or third-degree atrioventricular (AV) block unless treated with a permanent pacemaker, e) complete left bundle branch block (LBBB), f) history of long QT Syndrome or a family member with this condition, g) if baseline QTc > 470 ms, average of triplicate electrocardiogram (ECG) recordings is necessary; if average value of QTc is > 470 ms, patient is ineligible for the study; h) serum potassium, magnesium, and calcium levels outside the laboratory's reference range
+Other significant electrocardiogram (ECG) abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block
+A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), torsade de pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD)
+No myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
+Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, Wolff-Parkinson-White [WPW] syndrome, or torsade de pointes), or prolonged QTc interval on pre-entry ECG (>450 msec). If the automated reading is prolonged (i.e., >450 msec), the ECG should be manually over-read.
+No myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
+Patient has active cardiac disease or cardiac dysfunction including any of the following:\r\n* Left ventricular ejection fraction (LVEF) 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* Corrected QT interval (QTc) > 480 msec on screening electrocardiogram (ECG) (using the QTc Fridericia's [QTcF] formula)\r\n* Angina pectoris that requires the use of anti-anginal medications\r\n* Ventricular arrhythmias except for benign premature ventricular contractions\r\n* Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication\r\n* Conduction abnormality requiring a pacemaker\r\n* Valvular disease with documented compromise in cardiac function\r\n* Symptomatic pericarditis\r\n* Myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall motion abnormalities on assessment of left ventricular ejection fraction function\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Congenital long QT syndrome
+Inability to determine the QTcF interval Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block).
+Clinically significant cardiac disease or impaired cardiac function such as: \r\n* Congestive heart failure (CHF) requiring treatment (New York Heart Association >= grade 2), left ventricular ejection fraction (LVEF) =< 50% dose determined by multi-gated acquisition (MUGA) scan or echocardiogram, or uncontrolled arterial hypertension defined by blood pressure greater than 140/80 mmHg at rest (average of 3 consecutive readings) \r\n* History or current evidence of clinically significant cardiac arrhythmias, atrial fibrillation and/or conduction abnormality, (e.g. congenital long QT syndrome, high grade/complete atrioventricular [AV] blockage)\r\n* Acute coronary syndrome (including myocardial infarction, unstable angina, coronary artery bypass graft [CABG], for coronary angiography angioplasty and stenting), < 3 months prior to screening\r\n* QT interval adjusted according to Fridericia (QTcF) > 480 msec on screening electrocardiogram (EKG)
+Significant cardiovascular disease, including:\r\n* Cardiac failure New York Heart Association (NYHA) class III or IV\r\n* Myocardial infarction, severe or unstable angina within 6 months prior to study day 1\r\n* History of serious arrhythmia (i.e., ventricular tachycardia, or ventricular fibrillation)\r\n* Cardiac arrhythmias requiring anti-arrhythmic medications
+History or evidence of cardiovascular risk including any of the following:\r\n* A corrected QT interval using the Bazett’s formula QTcB >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias or patients that require medications with a narrow therapeutic window, atrial fibrillation and/or conduction abnormality, e.g. congenital long QT syndrome, high-grade/complete atrioventricular (AV)-blockage (exception: patients with chronic atrial fibrillation with heart rate less than 100 for > 30 days prior to randomization are eligible)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary artery bypass graft (CABG) coronary angioplasty, or stenting within 6 months prior to randomization\r\n* Current class II or higher congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic > 150 mmHg and/or diastolic > 90 mmHg despite adequate attempts at anti-hypertensive therapy
+Patients with clinically significant cardiovascular disease; this includes: \r\n* Uncontrolled hypertension, defined as systolic greater than or equal to 160 mm Hg or diastolic greater than or equal to 100 mm Hg despite antihypertensive medications \r\n* Myocardial infarction or unstable angina within 6 months prior to the first date of study treatment\r\n* New York Heart Association (NYHA) class II or greater congestive heart failure\r\n* History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or serious cardiac arrhythmia requiring medication; this does not include asymptomatic atrial fibrillation with controlled ventricular rate\r\n* Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms; \r\n** Note: if initial QTcF is found to be > 500 ms, two additional electrocardiograms (ECGs) separated by at least 3 minutes should be performed; if the average of these three consecutive results for QTcF is less than or equal to 500 ms, the subject meets eligibility in this regard
+Patients with New York Heart Association (NYHA) class III and IV heart failure, myocardial infarction in the preceding 6 months, and significant conduction abnormalities, including but not limited to atrial fibrillation, 2nd degree atrioventricular (AV) block type II, 3rd degree block, torsades de pointes, QT prolongation (corrected QT [QTc] > 450 msec), sick sinus syndrome, ventricular tachycardia, symptomatic bradycardia (heart rate < 50 beats per minute [bpm]), hypotension, light headedness and syncope; patients with atrial fibrillation will be excluded even if they are rate-controlled; if there are any active cardiac issues, cardiology consultation will be obtained for clearance
+Clinically significant cardiovascular disease including:\r\n* Acute coronary syndrome within 6 months of screening visit\r\n* Hypotension defined as a systolic blood pressure < 86 mmHg\r\n* Bradycardia defined as a heart rate of < 50 beats per minute, unless pharmaceutically induced and thus reversible (i.e. beta blockers)\r\n* Uncontrolled angina (requiring escalating doses of nitrates) within 3 months of screening visit\r\n* Congestive heart failure New York Heart Association (NYHA) class III or IV or subjects with a history of congestive heart failure NYHA class III or IV, unless screening echocardiogram (ECHO) results in left ventricular ejection fraction that >= 45%\r\n* History of clinically significant ventricular arrhythmias (e.g. ventricular tachycardia, ventricular fibrillation, torsades de pointes)\r\n* Prolonged corrected QT interval by the Fridericia correction formula (QTcF) on screening electrocardiogram (EKG) > 470 msec\r\n* History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place
+Clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:\r\n* Any history of myocardial infarction, stroke, or revascularization\r\n* Unstable angina or transient ischemic attack within 6 months prior to registration\r\n* Congestive heart failure within 6 months prior to registration, or left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards within 6 months prior to registration\r\n* History of clinically significant (as determined by the treating physician) atrial arrhythmia\r\n* Any history of ventricular arrhythmia\r\n* Active venous thromboembolism including deep venous thrombosis or pulmonary embolism that is not amenable to treatment with anticoagulants\r\n* Patients with congenital prolonged QT syndromes and abnormal baseline prolonged corrected QT (QTc) (> 450 ms in men and > 470 ms in women)\r\n* Patients with an ejection fraction =< 50% as assessed by a baseline echocardiogram
+Patient has known active cardiac disease including any of the following:\r\n* Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) \r\n* Corrected QT interval (QTc) > 480 msec on screening echocardiogram (ECG) (using the QT interval corrected by the Fridericia formula [QTcF])\r\n* Angina pectoris that requires the use of anti-anginal medication\r\n* Ventricular arrhythmias except for benign premature ventricular contractions\r\n* Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication\r\n* Conduction abnormality requiring a pacemaker\r\n* Valvular disease with document compromise in cardiac function \r\n* Symptomatic pericarditis
+Patient has a history of cardiac dysfunction including any of the following:\r\n* Myocardial infraction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular ejection fraction (LVEF) function\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy
+History of myocardial infarction =< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
+Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
+Serious cardiac illness or medical condition including but not confined to: Uncontrolled arrhythmias (e.g. ventricular tachycardia, high-grade atrioventricular (AV)-block, supraventricular arrhythmias which are not adequately rate-controlled);
+Patients who have experienced any of the following procedures or conditions currently or in the preceding 12 months: a) coronary artery bypass graft; b) angioplasty; c) vascular stent; d) myocardial infarction; e) angina pectoris; f) congestive heart failure New York Heart Association grade >= 2; g) ventricular arrhythmias requiring continuous therapy; h) supraventricular arrhythmias including atrial fibrillation, which are uncontrolled; i) hemorrhagic or thrombotic stroke, including transient ischemic attacks or any other central nervous system bleeding
+Clinically significant heart disease defined as:\r\n* Myocardial infarction within 6 months of screening visit\r\n* Uncontrolled angina within 3 months of screening visit\r\n* Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subjects with history of congestive heart failure NYHA class 3 or 4 in the past, or history of anthracycline or anthracenedione (mitoxantrone) treatment, unless a screening echocardiogram or multi-gated acquisition scan (MUGA) performed within three months of the screening visit results in a left ventricular ejection fraction that is >= 45%\r\n* History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsade de pointes)\r\n* Prolonged corrected QT interval by the Fridericia correction formula (QTcF) on the screening electrocardiogram (ECG) > 470 msec\r\n* History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place\r\n* Hypotension (systolic blood pressure < 86 mmHg) or bradycardia with a heart rate of < 50 beats per minute on the screening ECG, unless pharmaceutically induced and thus reversible (i.e. beta blockers) or known, chronic asymptomatic baseline heart rate\r\n* Uncontrolled hypertension as indicated by a resting systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg at the screening visit
+Myocardial infarct within 6 months before enrollment, New York Heart Association (NYHA) class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities
+Unstable cardiovascular function:\r\n* Symptomatic ischemia, or\r\n* Uncontrolled clinically significant conduction abnormalities (e.g.: ventricular tachycardia on antiarrhythmics are excluded and 1st degree atrioventricular [AV] block or asymptomatic left anterior fascicular block [LAFB]/right bundle branch block [RBBB] will not be excluded), or\r\n* Congestive heart failure (CHF) of New York Heart Association (NYHA) class >= 3, or\r\n* Myocardial infarction (MI) within 3 months of cycle 1 day 1 dose
+Subjects with acute coronary syndrome within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities are not eligible; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
+Significant screening ECG abnormalities including left bundle branch block, 2nd degree AV block type II, 3rd degree block, Grade 2 or higher bradycardia, and QTc > 480 msec.
+The patient has cardiac conditions as follows: uncontrolled hypertension (blood pressure [BP] > 160/100) despite optimal therapy, uncontrolled angina, ventricular arrhythmias, congestive heart failure (New York Heart Association class II or above), baseline left ventricular ejection fraction (LVEF) =< 50%, prior or current cardiomyopathy, atrial fibrillation with heart rate > 100 beats per minute (bpm), unstable ischemic heart disease (myocardial infarction [MI] within 6 months prior to starting treatment or angina requiring use of nitrates more than once weekly)
+Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiograms, e.g. complete left bundle branch block, third degree heart block, second degree heart block, PR interval >250 msec.
+Unstable cardiovascular function:\r\n* Symptomatic ischemia, or\r\n* Uncontrolled clinically significant conduction abnormalities (e.g.: ventricular tachycardia on antiarrhythmics are excluded and first (1st) degree atrioventricular (AV) block or asymptomatic left anterior fascicular block [LAFB]/right bundle branch block [RBBB] will not be excluded)\r\n* Congestive heart failure (CHF) of New York Heart Association (NYHA) class >= 3, or\r\n* Myocardial infarction (MI) within 3 months of initiation of therapy
+History of myocardial infarction =< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
+Have a personal history within the last 12 months of any of the following conditions: syncope of cardiovascular etiology, ventricular tachycardia, ventricular fibrillation, or sudden cardiac arrest
+Unstable angina or myocardial infarction within 4 months prior to the first day of treatment, the New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or grade 3 conduction system abnormalities unless subject has a pacemaker
+Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure (New York Heart Association [NYHA] class III or IV), unstable angina pectoris, myocardial infarction within 6 months prior to enrollment, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
+Unacceptable cardiac risk factors defined by any of the following criteria: patients with congenital long QT syndrome, any history of ventricular fibrillation or torsade de pointes, bradycardia defined as heart rate (HR) < 50 bpm, left ventricular ejection fraction < 30%
+Subjects with a known history of severe and/or uncontrolled ventricular arrhythmias.
+Clinically significant cardiovascular disease including:\r\n* Myocardial infarction within 6 months\r\n* Uncontrolled angina within 3 months\r\n* Congestive heart failure New York Heart Association (NYHA) class 3 of 4, or patients with history of congestive heart failure NYHA class 3 or 4 in the past, unless screening echocardiogram or multi-gated acquisition scan performed within 3 months results in a left ventricular ejection fraction that is >= 45%\r\n* History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes)\r\n* History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place\r\n* Hypotension as indicated by systolic blood pressure < 86 millimeters of mercury (mmHg) at the screening visit\r\n* Bradycardia as indicated by a heart rate of < 50 beats per minute on the screening electrocardiogram (ECG)\r\n* Uncontrolled hypertension as indicated by systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg
+Patients with active cardiac disease including any of the following:\r\n* Left ventricular ejection fraction < 50% as determined by multi gated acquisition scan (MUGA) scan or echocardiogram\r\n* Corrected QT (QTc) > 480 msec on screening ECG (using the corrected QT interval using the Fridericia's [QTcF] formula)\r\n* Active angina pectoris\r\n* Ventricular arrhythmias except for benign premature ventricular contractions\r\n* Supraventricular or nodal arrhythmias or any conduction abnormality requiring a pacemaker or automatic implantable cardioverter defibrillator (AICD)\r\n* Valvular disease with documented compromise in cardiac function\r\n* Symptomatic pericarditis\r\n* Myocardial infarction within the past 6 months\r\n* Congestive heart failure (New York Heart Association [NYHA] functional classification III-IV)
+Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes);
+Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; before study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
+Patients with clinically significant cardiac disease or impaired cardiac function are not eligible for participation; this includes patients with:\r\n* Congestive heart failure (CHF) requiring treatment (New York Heart Association [NYHA] grade >= 2)\r\n* Left ventricular ejection fraction (LVEF) < 50% as determined by multi-gated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* Uncontrolled arterial hypertension defined by blood pressure > 140/100 mm Hg at rest (average of 3 consecutive readings)\r\n* History or current evidence of unstable, clinically significant cardiac arrhythmias or patients that require medications with a narrow therapeutic window, atrial fibrillation and/or conduction abnormality (e.g. congenital long QT syndrome, high-grade/complete atrioventricular [AV]-blockage)\r\n* Acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft [CABG], coronary angioplasty, or stenting), < 3 months prior to screening\r\n* QTc > 460 msec on screening
+Significant screening ECG abnormalities including left bundle branch block, 2nd degree AV block type II, 3rd degree block, Grade 2 or higher bradycardia, and QTc ? 480 ms.
+Clinically significant cardiovascular disease, including:\r\n* Myocardial infarction within 3 months of enrollment\r\n* Uncontrolled angina within 3 months of enrollment\r\n* Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multi-gated acquisition scan performed within 3 months results in a left ventricular ejection fraction >= 45%\r\n* History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes);\r\n* History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place\r\n* Hypotension as indicated by systolic blood pressure < 86 mmHg on 2 consecutive measurements at the screening visit\r\n* Bradycardia as indicated by a heart rate < 50 beats per minute at the screening visit;\r\n* Uncontrolled hypertension as indicated by systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg on 2 consecutive measurements at the screening visit;\r\n* Electrocardiogram (EKG) demonstrating equal to or greater than grade III toxicity according the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
+No unstable angina or myocardial infarction within 4 months prior to cycle 1 day 1, New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or grade 3 conduction system abnormalities unless subject has a pacemaker
+Participants with a history of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, uncontrolled atrial fibrillation, left bundle branch block) that is symptomatic or requires treatment (except for controlled atrial fibrillation)
+Any known cardiac abnormalities such as:\r\n* Congenital long QT syndrome\r\n* Corrected QT (QTc) interval >= 500 milliseconds\r\n* Patients taking drugs leading to significant QT prolongation \r\n* Myocardial infarction within 6 months of course 1 day 1 (C1D1); (subjects with a history of myocardial infarction between 6 and 12 months prior to C1D1 who are asymptomatic and have had a negative cardiac risk assessment [treadmill stress test, nuclear medicine stress test, or stress echocardiogram] since the event, may participate)\r\n* Other significant electrocardiogram (ECG) abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min)\r\n* Symptomatic coronary artery disease (CAD), e.g., angina Canadian class II-IV; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present\r\n* An ECG recorded at screening showing evidence of cardiac ischemia (ST depression of >= 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present\r\n* Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II to IV definitions and/or ejection fraction < 40% by multigated acquisition (MUGA) scan or < 50% by echocardiogram and/or MRI;\r\n* A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD)\r\n* Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes\r\n* Uncontrolled hypertension, i.e., blood pressure (BP) of >= 160/95; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria; or\r\n* Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)
+Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG eg, complete left bundle branch block, third degree heart block
+Known significant cardiac abnormalities, including:\r\n* History or presence of sustained ventricular tachyarrhythmia (participants with a history of atrial arrhythmia are eligible but should be discussed with Dr. Laubach prior to enrollment)\r\n* Any history of ventricular fibrillation or torsades de pointes\r\n* Bradycardia defined as heart rate (HR) < 50 beats per minute (bpm); participants with pacemakers are eligible if HR >= 50 bpm\r\n* QTcF interval >= 450 milliseconds on screening electrocardiogram (ECG);\r\n* Right bundle branch block + left anterior hemiblock (bifascicular block)\r\n* Participants with myocardial infarction or unstable angina =< 6 months prior to starting study drug\r\n* Other clinically significant heart disease (e.g. congestive heart failure [CHF] New York [NY] Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
+History or evidence of cardiovascular risk including any of the following:\r\n* Corrected QT using Fridericia's formula (QTcF) >= 480 msec (>= 500 msec for subject with bundle branch block)\r\n* History or evidence of current clinically significant uncontrolled arrhythmias; exception: subjects with controlled atrial fibrillation for > 30 days prior to randomization are eligible\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization\r\n* History or evidence of current >= class II congestive heart failure as defined by New York Heart Association (NYHA)
+History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality in the previous 12 months.
+History of myocardial infarction =< 180 days (6 months), or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
+Clinically significant cardiovascular disease including:\r\n* Myocardial infarction within 6 months of screening visit\r\n* Uncontrolled angina within 3 months of screening visit\r\n* Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subjects with history of congestive heart failure NYHA class 3 or 4 in the past, or history of anthracycline or anthracenedione (mitoxantrone) treatment, unless a screening echocardiogram or multi-gated acquisition scan (MUGA) performed within three months of the screening visit results in a left ventricular ejection fraction that is >= 45%\r\n* History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsade de pointes)\r\n* Prolonged corrected QT interval by the Fridericia correction formula (QTcF) on the screening electrocardiogram (ECG) > 470 msec\r\n* History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place\r\n* Hypotension (systolic blood pressure < 86 mmHg or bradycardia with a heart rate of < 50 beats per minute on the screening ECG, unless pharmaceutically induced and thus reversible [i.e. beta blockers])\r\n* Uncontrolled hypertension as indicated by a resting systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg at the screening visit
+History or evidence of cardiovascular risk including any of the following: Acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to enrolment; clinically significant uncontrolled arrhythmias; however, subjects with controlled atrial fibrillation for >30 days prior to enrollment are eligible; class II or higher congestive heart failure as defined by the New York Heart Association (NYHA) criteria; left ventricular ejection fraction (LVEF) below the institutional LLN. If a LLN does not exist at an institution, then use LVEF <50%; abnormal cardiac valve morphology (?Grade 2) documented by ECHO; however, subjects with Grade 1 abnormalities (i.e., mild regurgitation/stenosis) may be entered on study but subjects with moderate valvular thickening should NOT be enrolled; corrected QT (QTc) interval for heart rate using Bazett-corrected QT interval (QTcB) >=480 msec; intracardiac defibrillator; treatment-refractory hypertension defined as a blood pressure (BP) >140/90 mmHg which may not be controlled by anti-hypertensive medication(s) and/or lifestyle modifications
+Patients who have any severe and/or uncontrolled medical conditions or other\r\nconditions that could affect their participation in the study such as:\r\n* Known cardiopulmonary disease defined as:\r\n** Unstable angina\r\n** Congestive heart failure (New York Hear Association [NYHA] class III or IV\r\n** Myocardial infarction (MI) within 6 months prior to first dose (patients who had ischemic heart disease such as acute chest syndrome [ACS], MI and/or revascularization greater than 6 months before screening and who are without cardiac symptoms may enroll)\r\n** Cardiomyopathy\r\n** Clinically significant arrhythmia:\r\n*** Polymorphic ventricular fibrillation or torsade de pointes\r\n*** Permanent atrial fibrillation [a fib], defined as continuous a fib >= 6 months\r\n*** Persistent a fib, defined as sustained a fib lasting > 7 days and/or requiring cardioversion in the 4 weeks before screening\r\n*** Grade 3 a fib defined as symptomatic and incompletely controlled medically, or controlled with device (e.g. pacemaker), or ablation\r\n*** Patients with paroxysmal a fib or < grade (Gr) 3 a fib for period of at least 6 months are permitted to enroll provided that their rate is controlled on a stable regimen\r\n*** Implantable cardioverter defibrillator\r\n** Moderate to severe aortic and/or mitral stenosis or other valvulopathy (ongoing)\r\n** Symptomatic pulmonary hypertension\r\n* Active infection requiring IV antibiotic, antiviral, or anti-fungal medications within 2 weeks of starting study drug\r\n* Known history of human immunodeficiency virus (HIV) seropositivity
+Impaired cardiac function or clinically significant cardiac diseases, including any of the following:\r\n* History or presence of ventricular tachyarrhythmia\r\n* Presence of unstable atrial fibrillation (ventricular response > 100 bpm) (NOTE: patients with stable atrial fibrillation are eligible, provided they do not meet any of the other cardiac exclusion criteria)\r\n* Clinically significant resting bradycardia (< 50 bpm)\r\n* Angina pectoris or acute myocardial infarction =< 3 months prior to registration\r\n* Other clinically significant heart disease (e.g., symptomatic congestive heart failure; uncontrolled arrhythmia or hypertension; history of labile hypertension or poor compliance with an antihypertensive regimen)
+No clinically significant cardiovascular disease including:\r\n* Myocardial infarction (MI) within 6 months\r\n* Uncontrolled angina within 3 months\r\n* Congestive heart failure (CHF) with New York Heart Association (NYHA) class 3 or 4, or patients with NYHA class 3 or 4 in the past, unless a screening echocardiogram (echo) or multi gated acquisition scan (MUGA) performed within three months demonstrates an ejection fraction (EF) > 45%\r\n* History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes)\r\n* History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place\r\n* Hypotension (systolic blood pressure [BP] < 86 mmHg) or bradycardia (< 50 beats per minute [bpm]) at screening \r\n* Uncontrolled hypertension (systolic BP > 170 mmHg or diastolic BP > 105 mmHg at screening)
+Unstable angina or myocardial infarction within 4 months prior to registration, New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or grade 3 conduction system abnormalities unless subject has a pacemaker
+Clinically significant heart disease as evidenced by:\r\n* Myocardial infarction within 6 months of enrollment\r\n* Uncontrolled angina within 6 months of enrollment\r\n* Congestive heart failure New York Heart Association (NYHA) class III or IV, or a history of congestive heart failure NYHA class III or IV in the past, unless a screening echocardiogram (ECHO) or multigated acquisition scan (MUGA) within 3 months results in a left ventricular ejection fraction >= 45%\r\n* Clinically significant ventricular arrhythmias\r\n* History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place\r\n* Bradycardia as indicated by a heart rate < 50 beats per minute at screening visit\r\n* Hypotension as indicated by systolic blood pressure (SBP) =< 85 on 2 consecutive measurements\r\n* Uncontrolled hypertension as indicated by SBP > 170 mmHg or diastolic blood pressure (DBP) > 105 mmHg on 2 consecutive measurements at screening visit
+PART B: Any history of ventricular arrhythmia (other than premature ventricular complexes)
+History of myocardial infarction =< 180 days prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
+Clinically significant cardiovascular disease including:\r\n* Myocardial infarction within 6 months prior to screening;\r\n* Uncontrolled angina within 3 months prior to screening;\r\n* Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or patients with history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) performed within 3 months results in a left ventricular ejection fraction that is >= 45%\r\n* History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes)\r\n* History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place\r\n* Hypotension as indicated by systolic blood pressure < 86 mmHg at the screening visit\r\n* Bradycardia as indicated by a heart rate of < 50 beats per minute at the screening visit \r\n* Uncontrolled hypertension as indicated by systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg at the screening visit
+Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
+Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
+Subjects with a known history of severe and/or uncontrolled ventricular arrhythmias.
+History or evidence of cardiovascular risks including any of the following:\r\n* QT interval corrected for heart rate using the Bazett’s formula QTcB >= 480 msec\r\n* History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within the past 24 weeks prior to randomization\r\n* History or evidence of current class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Intra-cardiac defibrillators\r\n* Abnormal cardiac valve morphology (>= grade 2) documented by ECHO; (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study\r\n* History or evidence of current clinically significant uncontrolled cardiac arrhythmias; clarification: subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible\r\n* Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti- hypertensive therapy
+Active or severe hepatic, cardiovascular, or cerebrovascular disease, including myocardial infarction within 6 months prior to enrollment, have New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
+Patients must not have a history of acute coronary syndromes (including unstable angina), myocardial infarction within 6 months, coronary angioplasty, or stenting within the past 24 weeks; class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system; or history of known cardiac arrhythmias (such as atrial fibrillation) unless it has been stably controlled for > 30 days prior to registration; abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis]) can be entered on study; subjects with moderate valvular thickening are not eligible
+Significant cardiovascular disease, including\r\n* Uncontrolled hypertension: systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg documented on 2 consecutive measurements taken at least 24 hours apart\r\n* Myocardial infarction, severe angina, or unstable angina within 6 months prior to administration of first dose of study drug\r\n* History of class III or IV congestive heart failure, as defined by the New York Heart Association\r\n* History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation)\r\n* Cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well-controlled with anti-arrhythmic medication; and/or\r\n* Coronary or peripheral artery bypass graft within 6 months of screening
+Clinically significant cardiac disease or impaired cardiac function, such as:\r\n* Congestive heart failure requiring treatment (e.g., New York Heart Association class II, III or IV)\r\n* Acute coronary syndromes < 3 months prior to screening (including myocardial infarction, unstable angina, coronary artery bypass graft, coronary angioplasty, or stenting)\r\n* Uncontrolled arterial hypertension defined by blood pressure > 140/100 mm Hg at rest (average of 3 consecutive readings)\r\n* History or current evidence of unstable, clinically significant cardiac arrhythmias or patients that require medications with a narrow therapeutic window, atrial fibrillation and/or conduction abnormality, e.g. congenital long QT syndrome, high-grade/complete atrioventricular (AV) blockage\r\n* Corrected QT interval (QTc) > 480 msec on screening electrocardiogram (ECG)
+Participants with any of the following cardiac conditions:\r\n* History of long QT syndrome\r\n* Frederica corrected QT interval (QTcF) >= 450 ms during screening electrocardiogram (ECG)\r\n* History of clinically manifest ischemic heart disease including myocardial infarction, stable or unstable angina pectoris, coronary arteriography or cardiac stress testing/imaging with findings consistent with infarction or clinically significant coronary occlusion =< 6 months prior to study start\r\n* History of heart failure or left ventricular (LV) dysfunction (left ventricular ejection fraction [LVEF] =< 45%) by multi gated acquisition scan (MUGA) or echocardiogram (ECHO)\r\n* Clinically significant ECG abnormalities including one or more of the following: left bundle branch block (LBBB), right bundle branch block (RBBB) with left anterior hemiblock (LAHB); ST segment elevations or depressions > 1 mm, or 2nd (Mobitz II) or 3rd degree atrioventricular (AV) block\r\n* History and presence of atrial fibrillation, atrial flutter or ventricular arrhythmias including ventricular tachycardia or torsades de pointes\r\n* Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with a hypertensive regimen)\r\n* Clinically significant resting bradycardia (< 50 beats per minute)\r\n* Patients who are currently receiving treatment with any medication which has a relative risk or prolonging the corrected QT (QTc) interval or inducing torsades de pointes and cannot be switched or discontinued to an alternative drug prior to commencing AUY922 dosing\r\n* Patients who are on a cardiac pacemaker
+Impaired cardiac function including any of the following:\r\n* Screening electrocardiogram (ECG) with a corrected QT interval (QTc) > 450 msec \r\n* Bradycardia defined as heart rate (HR) < 50 beats per minute (bpm)\r\n* Right bundle branch block + left anterior hemiblock (bifascicular block)\r\n* Patients with myocardial infarction or unstable angina < 3 months prior to starting study drug\r\n* Congestive heart failure (CHF) New York (NY) Heart Association class III or IV
+Myocardial infarction within 6 months prior to enrollment, or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; NOTE: Prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
+Patient has active cardiac disease including any of the following: \r\n* History of clinically significant heart failure (previously assessed) with a left ventricular ejection fraction (LVEF) of < 50% as determined by multiple grated acquisition (MUGA) scan or echocardiogram (ECHO) \r\n* Corrected QT (QTc) > 480 msec on screening electrocardiogram (ECG) (using the Fridericia QT correction [QTcF] formula)\r\n* Angina pectoris that requires the use of anti-anginal medication\r\n* Ventricular arrhythmias except for benign premature ventricular contractions\r\n* Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication\r\n* Conduction abnormality requiring a pacemaker\r\n* Valvular disease with document compromise in cardiac function \r\n* Symptomatic pericarditis
+Myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
+Uncontrolled intercurrent illness including, but not limited to:\r\n* Ongoing or active infection requiring parenteral antibiotics\r\n* Impairment of lung function (chronic obstructive pulmonary disease [COPD] > grade 2, lung conditions requiring oxygen therapy)\r\n* Symptomatic congestive heart failure (class III or IV of the New York Heart Association classification for heart disease)\r\n* Known / previously documented left ventricular ejection fraction (LVEF) < 50% within 6 months of trial enrollment\r\n* Unstable angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months\r\n* Uncontrolled hypertension within 2 weeks of study initiation (systolic blood pressure > 180 mm Hg or diastolic blood pressure > 110 mm Hg, found on two consecutive measurements separated by a 1 or 2-week period despite adequate medical support)\r\n* Clinically significant cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia that is symptomatic or requires treatment [National Cancer Institute -Common Terminology Criteria for Adverse Events, version 4.0, grade 3])\r\n* QT interval corrected for heart rate using Fridericia's formula (QTcF) >= 480 msec on screening electrocardiogram (EKG)\r\n* Known history of QT/corrected QT interval (QTc) prolongation or torsades de pointes (TdP)\r\n* ST depression or elevation of >= 1.5 mm in 2 or more leads\r\n* Diarrhea of any cause >= Common Terminology Criteria for Adverse Events (CTCAE) grade 2\r\n* Psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements including maintenance of a compliance/pill diary\r\n* Patients with symptomatic brain metastases (patients with a history of brain metastases must be clinically stable for more than 4 weeks from completion of radiation treatment)\r\n* Patients with known history of chronic liver or renal failure\r\n* Patients with known history of chronic or acute pancreatitis
+Participants with following cardiac criteria:\r\n* History of long QT syndrome\r\n* Fridericia corrected QT interval (QTcF) >= 450 ms during screening electrocardiogram (ECG)\r\n* History of clinically manifest ischemic heart disease including myocardial infarction, stable or unstable angina pectoris, coronary arteriography or cardiac stress testing/imaging with findings consistent with infarction or clinically significant coronary occlusion =< 6 months prior to study start\r\n* History of heart failure or left ventricular (LV) dysfunction (LV ejection fraction [EF] =< 45%) by multi gated acquisition scan (MUGA) or echocardiogram (ECHO)\r\n* Clinically significant ECG abnormalities including one or more of the following: left bundle branch block (LBBB), right bundle branch block (RBBB) with left anterior hemiblock (LAHB); ST segment elevations or depressions > 1mm, or 2nd (Mobitz II) or 3rd degree atrioventricular block (AV) block\r\n* History and presence of atrial fibrillation, atrial flutter or ventricular arrhythmias including ventricular tachycardia or torsades de pointes\r\n* Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with a hypertensive regimen)\r\n* Clinically significant resting bradycardia (< 50 beats per minute)\r\n* Participants who are currently receiving treatment with any medication which has a relative risk or prolonging the QTcF interval or inducing torsades de pointes (as listed in protocol) and cannot be switched or discontinued to an alternative drug prior to commencing AUY922 dosing\r\n* Participants who are on a cardiac pacemaker
+Significant or uncontrolled congestive heart failure (CHF), myocardial infarction, significant ventricular arrhythmias within the last six months or significant pulmonary dysfunction.
+The following cardiac abnormalities:\r\n* Congenital long QT syndrome\r\n* Corrected QT (QTc) interval >= 480 milliseconds\r\n** A QTc interval between 480-499 milliseconds (msec) in the presence of a bundle branch block (BBB) or pacemaker is eligible in phase IIa after discussion with MSK principal investigator\r\n* Myocardial infarction within 6 months of cycle one, day one (C1D1); subjects with a history of myocardial infarction between 6 and 12 months prior to C1D1 who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event may participate\r\n* Other significant electrocardiogram (ECG) abnormalities including second (2nd) degree atrio-ventricular (AV) block type II, third (3rd) degree AV block\r\n* Symptomatic coronary artery disease (CAD), e.g., angina Canadian class II-IV; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present\r\n* An ECG recorded at screening showing evidence of cardiac ischemia (ST depression of >= 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present\r\n* Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II to IV definitions and/or ejection fraction < 45% by multi gated acquisition scan (MUGA), ECG, or cardiac magnetic resonance imaging (MRI)\r\n* A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), torsades de pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD)\r\n* Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes\r\n* Uncontrolled hypertension, i.e., blood pressure (BP) of >= 170/95; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria\r\n* Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)
+Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
+History or evidence of cardiovascular risk including any of the following:\r\n* Corrected QT using Bazett's method (QTcB) >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias; exception: subjects with controlled atrial fibrillation for > 30 days prior to enrollment are eligible\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to enrollment\r\n* History or evidence of current >= class II congestive heart failure as defined by New York Heart Association (NYHA)\r\n* Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy\r\n* Patients with intra-cardiac defibrillators\r\n* Cardiac metastases
+Patients with New York Heart Association (NYHA) class III and IV heart failure, myocardial infarction in the preceding 6 months, and conduction abnormalities, including but not limited to atrial fibrillation, atrioventricular (AV) block, QT prolongation, sick sinus syndrome, ventricular tachycardia
+Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities (not including 1st degree atrioventricular [AV]-block, Wenckebach type 2nd degree heart block, or left bundle branch block; prior to study entry, any electrocardiogram [ECG] abnormality at screening has to be documented by the investigator as not medically relevant); Note: there is no lower limit of left ventricular ejection fraction below which patients are excluded from participation
+History or evidence of cardiovascular risk including any of the following: \r\n* Corrected QT (QTc) >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias \r\n** Exception: subjects with controlled atrial fibrillation for > 30 days prior to D1 of study treatment are eligible\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to study entry\r\n* Patients with history of hypertension MUST have hypertension adequately controlled (BP < 140/90) with appropriate anti-hypertensive therapy or diet prior to study entry\r\n**Note: To be eligible a subject must have an average of BP below < 140/90 based on 3 separate measures; if the subject has a record of BP recordings taken at home and in their medical record, =< 20% of BPs taken should have numbers > 140/90\r\n* Patients with intra-cardiac defibrillators or permanent pacemakers\r\n* Known cardiac metastases\r\n* Abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study
+Ejection fraction (EF) >= 50% and no uncontrolled angina, symptomatic ventricular arrhythmias, or electrocardiogram (ECG) evidence of active ischemia
+Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:\r\n* With permanent cardiac pacemaker\r\n* Resting bradycardia defined as < 50 beats per minute\r\n* Corrected QT using Fridericia's method (QTcF) > 480 msec on screening electrocardiogram (ECG)\r\n* Complete left bundle branch block, bifascicular block\r\n* Any clinically significant ST segment and/or T-wave abnormalities\r\n* Presence of unstable atrial fibrillation (ventricular response rate > 100 beats per minute [bpm]); patients with stable atrial fibrillation can be enrolled provided they do not meet other cardiac exclusion criteria\r\n* Symptomatic congestive heart failure (New York Heart Association [NYHA] class III-IV)
+Patients who have had a myocardial infarction within 6 months of enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
+Patient must not have had a myocardial infarction within 6 months prior to enrollment or have New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
+Patient had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
+Concurrent medical condition which may increase the risk of toxicity, including:\r\n* Pleural or pericardial effusion of any grade at the time of screening for study\r\n* Cardiac symptoms; any of the following should be considered for exclusion:\r\n** Uncontrolled angina, congestive heart failure or myocardial infarction (MI) within (6 months)\r\n** Diagnosed congenital long QT syndrome\r\n** Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
+Ejection fraction (EF) of < 40%, myocardial infarction (MI) within past 3 months, uncontrolled angina, severe uncontrolled ventricular arrythmias, or ECG evidence of acute ischemia.
+History of complex ventricular or supraventricular arrhythmias
+Serious cardiac illness, defined as follows:\r\n* Clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or indwelling temporary pacemaker\r\n* Ventricular tachycardia or a supraventricular tachycardia that requires treatment with a class Ia antiarrhythmic drug (eg, quinidine, procainamide, disopyramide) or class III antiarrhythmic drug (e.g. sotalol, amiodarone, dofetilide); use of other antiarrhythmic drugs is permised\r\n* Use of medications that have been linked to the occurrence of torsades de pointes; investigators should note that Zofran (ondansetron) has been linked to corrected QT (QTc) prolongation and the occurrence of torsades de pointes; therefore it should not be used in patients being treated with ganetespib; the use of all other serotonin 5 HT3 antagonists is acceptable (e.g., palonosetron, granisetron, tropisetron)\r\n* Second-or third degree atrioventricular block (AV block) unless treated with a permanent pacemaker\r\n* Complete left bundle branch block (LBBB)\r\n* History of long QT syndrome or a family member with this condition
+Any known cardiac abnormalities such as:\r\n* Congenital long QT syndrome\r\n* Corrected QT (QTc) interval >= 500 milliseconds;\r\n* Myocardial infarction within 6 months of cycle 1, day 1 (C1D1); subjects with a history of myocardial infarction between 6 and 12 months prior to C1D1 who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event may participate;\r\n* Other significant electrocardiogram (ECG) abnormalities including second (2nd) degree atrio-ventricular (AV) block type II, third (3rd) degree AV block, or bradycardia (ventricular rate less than 50 beats/min);\r\n* Symptomatic coronary artery disease (CAD), e.g., angina; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;\r\n* An ECG recorded at screening showing evidence of cardiac ischemia (ST depression, depression of >= 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;\r\n* Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II to IV definitions and/or ejection fraction < 40% by multi gated acquisition scan (MUGA) scan or < 50% by echocardiogram and/or magnetic resonance imaging (MRI);\r\n* A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), torsade de pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD);\r\n* Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes;\r\n* Uncontrolled hypertension, i.e., blood pressure (BP) of >= 160/95; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria; or\r\n* Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)
+Abnormal electrocardiogram (EKG): severe uncontrolled ventricular arrhythmias, or evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any EKG abnormality at screening has to be documented by the investigator as not medically relevant
+Any history of ventricular fibrillation or torsade de pointes
+Myocardial infarction within 6 months prior to signing consent or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiograph (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
+Impaired cardiac function or clinically significant cardiac diseases, including any one of the following: history or presence of sustained ventricular tachyarrhythmia; any history of ventricular fibrillation or torsade de pointes; bradycardia defined as heart rate (HR) < 50 beats per minute (bpm); patients with pacemakers are eligible if heart rate (HR) >= 50 bpm; screening ECG with a corrected QT using Fridericia's formula (QTcF) > 450 msec, right bundle branch block + left anterior hemiblock (bifascicular block), patients with myocardial infarction or unstable angina =< 6 months prior to starting study drug, other clinically significant heart disease (e.g., congestive heart failure [CHF] New York Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
+Patients must not have a history of heart block or cardiac arrhythmia, including asymptomatic arrhythmias and atrial fibrillation/flutter.
+Have a personal history of any of the following conditions: presyncope or syncope of either unexplained or cardiovascular etiology, ventricular arrhythmia (including but not limited to ventricular tachycardia and ventricular fibrillation), sudden cardiac death or sudden cardiac arrest
+Ejection fraction (EF) >= 40%, no uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
+No uncontrolled angina, severe uncontrolled ventricular or arterial arrhythmias, or any evidence of acute ischemia or active conduction system abnormalities (rate controlled atrial fibrillation is not an exclusion)
+History of clinically significant ventricular arrhythmias or active ventricular arrhythmia requiring medication
+Significant heart disease defined as:\r\n* Significant coronary arterial disease\r\n** Myocardial infarction in the last 6 months, angina in the previous 3 months,\r\n** Troponin elevation at level of myocardial infarction as defined by the manufacturer\r\n** Ischemic changes on electrocardiogram (ECG)\r\n* Atrio-ventricular block greater than 1st degree, in absence of pacemaker\r\n* Corrected QT interval (QTc) greater than 480 ms (CTCAE 4.0 grade 1 abnormality is acceptable)\r\n* History of ventricular arrhythmia\r\n* Left ventricular ejection fraction below the institutional limit of normal
+A history or evidence of cardiovascular risk including any of the following: Corrected QT (QTc) interval >=480 msecs History of acute coronary syndromes (including myocardial infarction or unstable angina) within 6 months prior to first dose of study treatment Coronary angioplasty, or stenting within the past 24 weeks; A history or evidence of current Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) guidelines; Treatment refractory hypertension defined as a blood pressure of systolic >140 mmHg and/or diastolic >90 mmHg which cannot be controlled by antihypertensive therapy; Abnormal cardiac valve morphology ( >=Grade 2) documented by echocardiogram (subjects with Grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study). Subjects with moderate valvular thickening should not be entered on study; Patients with intra-cardiac defibrillators A history or evidence of current clinically significant uncontrolled arrhythmias; Exception: Subjects with atrial fibrillation controlled for > 30 days prior to randomization are eligible. Uncontrolled medical conditions (i.e., diabetes mellitus, hypertension, etc.), psychological, familial, sociological, or geographical conditions that interfere with the subject's safety or obtaining informed consent or do not permit compliance with the protocol; or unwillingness or inability to follow the procedures required in the protocol;
+Impaired cardiac function or clinically significant cardiac diseases, including any one of the following: * History or presence of sustained ventricular tachyarrhythmia. (Patients with a history of atrial arrhythmia are eligible) * Any history of ventricular fibrillation or torsade de pointes * Bradycardia defined as heart rate (HR)< 50 bpm. Patients with pacemakers are eligible if HR >/= 50 bpm. * Screening electrocardiogram (ECG) with a corrected QT interval (QTc) or QTcF > 450 msec * Right bundle branch block + left anterior hemiblock (bifascicular block) * Patients with myocardial infarction or unstable angina </= 6 months prior to starting study drug * Other clinically significant heart disease (e.g., Congestive Heart Failure (CHF) New York Heart Association (NYHA) class III or IV , uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
+Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:\r\n* Left ventricular ejection fraction (LVEF) < 50% as determined by Multiple Grated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* ST depression or elevation of >= 1.5 mm in 2 or more leads\r\n* Congenital long QT syndrome\r\n* History or presence of ventricular arrhythmias or atrial fibrillation\r\n* Clinically significant resting bradycardia (< 50 beats per minutes)\r\n* Corrected QT interval (QTc) > 480 msec on screening electrocardiogram (ECG)\r\n* Complete left bundle branch block\r\n* Right bundle branch block + left anterior hemiblock (bifascicular block)\r\n* Unstable angina pectoris =<6 months prior to starting study drug\r\n* Acute myocardial infarction =< 6 months prior to starting study drug\r\n* Other clinically significant heart disease such as congestive heart failure requiring treatment (New York Heart Association [NYHA] class III or IV)
+High-risk uncontrolled arrhythmias (ventricular tachycardia, high-grade atrio-ventricular [AV]-block, supraventricular tachycardias which are not adequately rate-controlled)
+Patients who have congestive heart failure (New York Heart Association [NYHA] class III or IV), unstable angina, sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block or a history of acute myocardial infarction within the six months preceding enrollment
+Any history of ventricular fibrillation or torsade de pointes
+Any of the following cardiac abnormalities or history: a) clinically significant abnormal 12-lead electrocardiogram (ECG), QT interval (Bazett's corrected QT [QTCB]) > 480 ms, b) inability to measure QT interval on ECG, c) personal or family history of long QT syndrome, d) implantable pacemaker or implantable cardioverter defibrillator, e) resting bradycardia < 55 beats/min, f) history or evidence of current clinically significant uncontrolled arrhythmias; exception: subjects with controlled atrial fibrillation for > 30 days prior to randomization are eligible, g) history of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting, within 6 months prior to randomization, h) history or evidence of current >= class II congestive heart failure as defined by New York Heart Association (NYHA), i) treatment refractory hypertension defined as a blood pressure of systolic > 140 mm Hg and/or diastolic > 90 mm Hg which cannot be controlled by antihypertensive therapy, j) cardiac metastases
+Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class IIIB or IV heart failure uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities (not including 1st degree atrioventricular (AV)-block, Wenckebach type 2nd degree heart block, or left bundle branch block; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be evaluted by the investigator or an authorized physician sub-investigator); note: there is no lower limit of left ventricular ejection fraction below which patients are excluded from participation
+Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
+History of Torsades de pointes, ventricular tachycardia, or ventricular fibrillation
+History of Torsades de pointes, ventricular tachycardia, or ventricular fibrillation
+Uncontrolled or significant cardiovascular disease, including:\r\n* A myocardial infarction within 12 months of registration\r\n* Uncontrolled angina within 6 months of registration\r\n* Congestive heart failure within 6 months of registration\r\n* Diagnosed or suspected congenital long QT syndrome\r\n* Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes)\r\n* Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (> 470 msec)\r\n* Any history of second or third degree heart block (may be eligible if currently have a pacemaker)\r\n* Heart rate < 50/minute on pre-entry electrocardiogram\r\n* Uncontrolled hypertension
+Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
+Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
+Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
+Myocardial infarction within 6 months prior to enrollment, or New York Hospital Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active conduction system abnormalities
+Patients with significant atherosclerotic disease, as defined by: a) Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or ECG evidence of acute ischemia or active conduction system abnormalities. Any prior ECG abnormality at Screening has to be documented by the investigator as not medically relevant. b) Symptomatic congestive heart failure. c) Claudication limiting activity and d) History of cerebrovascular events within the last year (including TIA).
+Active Grade III-V cardiac failure as defined by the New York Heart Association Criteria. Uncontrolled angina, or MI within 6 months. Diagnosed or suspected congenital long QT syndrome. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes). Prolonged QTc interval on pre-entry electrocardiogram (> 470 msec). Patients currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes (unless these can be changed to acceptable alternatives)
+New York Heart Association (NYHA) cardiac class 3-4 heart disease as well as impaired cardiac function defined as: left ventricular ejection fraction (LVEF) < 45% as determined by multigated acquisition scan (MUGA) scan or electrocardiogram; complete left bundle branch block; use of cardiac pacemaker; ST depression of > 1 mm in 2 or more leads and/or T wave inversions in 2 or more continuous leads; congenital long QT syndrome; history of, or presence of significant ventricular or atrial tachyarrhythmias; clinically significant resting bradycardia (< 50 beats per minute [bpm]); corrected QT (QTc) > 450 msec on screening electrocardiogram (ECG) (using the Fridericia QTc [QTcF] formula); right bundle branch block plus left anterior hemiblock, bifascicular block; myocardial infarction within 12 months prior to starting AMN107 (nilotinib); unstable angina diagnosed or treated within the past 12 months; 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)
+No myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
+Patients with any clinically significant cardiovascular disease including the following:\r\n* Myocardial infarction or ventricular tachyarrhythmia within 6 months\r\n* Prolonged QTc > 480 msec by the Fridericia correction\r\n* Major conduction abnormality, such as 2nd or 3rd degree heart block or symptomatic bundle branch block, unless a cardiac pacemaker is present
+Any one of the following currently or in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack; symptomatic pulmonary embolism; congenital long QT syndrome, torsades de points, arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), right bundle branch block and left anterior hemiblock (bifascicular block), ongoing cardiac dysrhythmias of NCI CTCAE Grade >=2, atrial fibrillation of any grade, or QTc interval >470 msec at screening.
+Myocardial infarction, uncontrolled angina, uncontrolled ventricular arrhythmias, or ECG evidence of acute ischemia, within 6 months prior to the Month 1-Day 1 Visit
+Atrial fibrillation with a controlled ventricular rate (uncontrolled [i.e., >110 bpm] ventricular rate is not allowed [determined by an average of three beats in Lead II or 3 representative beats if Lead II is not representative of the overall ECG])
+History or evidence of cardiovascular risk including any of the following:\r\n* LVEF < institutional LLN or < 50%\r\n* A QT interval corrected for heart rate using the Bazett’s formula QTcB >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible)\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to study dose are eligible)\r\n* Patient with symptomatic bradycardia, or a history of clinically significant bradyarrhythmias such as sick sinus syndrome, second (2nd) degree atrioventricular (AV) block (Mobitz type 2)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to study dose\r\n* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Patients with intra-cardiac defibrillators\r\n* Known cardiac metastases
+Uncontrolled hypertension (blood pressure >150/100 mmHg despite optimal medical therapy) or any of the following within 12 months prior to registration: myocardial infarction, congenital long QT syndrome, torsade de points, arrhythmias, right bundle branch block and left anterior hemiblock uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, ongoing NCICTCAE Grade 2 cardiac dysrhythmias, atrial fibrillation or QTcF interval >470 msec.
+Persistent or clinically meaningful ventricular arrhythmias
+Known serious cardiac illness or medical conditions, including but not limited to:\r\n* Clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or indwelling temporary pacemaker\r\n* Ventricular tachycardia or a supraventricular tachycardia that requires treatment with a class Ia antiarrhythmic drug (eg, quinidine, procainamide, disopyramide) or class III antiarrhythmic drug (eg, sotalol, amiodarone, dofetilide); use of other antiarrhythmic drugs is permitted\r\n* Use of medications that have been linked to the occurrence of torsades de pointes\r\n* Second- or third-degree atrioventricular (AV) block unless treated with a permanent pacemaker\r\n* Complete left bundle branch block (LBBB)\r\n* History of long QT Syndrome or a family member with this condition\r\n* Corrected QT (QTc) > 470 ms (average of triplicate electrocardiogram [ECG] recordings); a consistent method of QTc calculation is recommended for each patient’s QTc measurements; QTcF (Fridericia’s formula) is preferred\r\n* Serum potassium, magnesium, and calcium levels outside the laboratory’s reference range
+Patient had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
+Participant with myocardial infarction within 6 months prior to enrollment or New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to the first dose of study treatment, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
+Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
+Unstable cardiovascular function that includes and may not be limited to:\r\n* Symptomatic myocardial ischemia, or\r\n* Uncontrolled clinically significant conduction abnormalities (e.g., ventricular tachycardia on antiarrhythmics are excluded and first [1st] degree atrioventricular [AV] block or asymptomatic left anterior fascicular block [LAFB]/right bundle branch block [RBBB] will not be excluded), or\r\n* Congestive heart failure (CHF) of New York Heart Association (NYHA) class 3, or\r\n* Myocardial infarction (MI) within 3 months
+Myocardial infarction, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia, within 6 months prior to the first dose of study drug
+Patients will be ineligible for treatment on this protocol if:\r\n* There is a history of a recent myocardial infarction (within one year)\r\n* There is a history of a past myocardial infarction (more than one year ago) along with current coronary symptoms requiring medications and/or evidence of depressed left ventricular function (left ventricular ejection fraction [LVEF] < 45% by echocardiogram [ECHO])\r\n* There is a current history of angina/coronary symptoms requiring medications and/or evidence of depressed left ventricular function (LVEF < 45% by ECHO)\r\n* There is clinical evidence of congestive heart failure requiring medical management (irrespective of ECHO results)
+History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes);
+Has acute myocardial infarction within 6 months before starting study drug, current or history of New York Heart Association Class III or IV heart failure; evidence of current uncontrolled cardiovascular conditions including cardiac arrhythmias, angina, pulmonary hypertension, or electrocardiogram (ECG) evidence of acute ischemia or active conduction system abnormalities; Fridericia's corrected QT interval > 475 milliseconds (msec) (males) or > 450 msec (females) on a 12-lead ECG during the Screening period; or abnormalities 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.
+Any of the following related to risk of torsades de pointes and sudden cardiac death:\r\n* History of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), torsades de pointes, or resuscitated cardiac arrest unless currently addressed with an implanted cardiac defibrillator\r\n* Concomitant treatment with an anti-arrhythmic agent to prevent or control arrhythmia; agents used for rate-control of atrial fibrillation are permitted provided that they are not prohibited due to potential drug interactions\r\n* Known congenital long QT syndrome\r\n* Second degree atrioventricular (AV) block type II, third degree AV block, or ventricular rate < 50 bpm or > 120 bpm
+Known serious cardiac illness or medical conditions, including but not limited to:\r\n* Clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or indwelling temporary pacemaker\r\n* Ventricular tachycardia or a supraventricular tachycardia that requires treatment with a class Ia antiarrhythmic drug (e.g., quinidine, procainamide, disopyramide) or class III antiarrhythmic drug (e.g., sotalol, amiodarone, dofetilide); use of other antiarrhythmic drugs is permitted\r\n* Use of medications that have been linked to the occurrence of Torsades de pointes \r\n* Second- or third-degree atrioventricular (AV) block unless treated with a permanent pacemaker\r\n* Complete left bundle branch block (LBBB)\r\n* History of long QT syndrome or a family member with this condition\r\n* Corrected QT (QTc) > 470 ms (average of triplicate electrocardiogram [ECG] recordings); a consistent method of QTc calculation must be used for each patient’s QTc measurements; QTcF (Fridericia’s formula) is preferred\r\n* Serum potassium, magnesium, or calcium levels in the following ranges:\r\n** Potassium < 3.4 or > 5.1 mmol/L\r\n** Magnesium < 1.4 or > 2.4 mg/dL\r\n** Calcium < 8.9 or > 10.5 mg/dL
+Patient has active cardiac disease including any of the following:\r\n* Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* QTc > 450 msec on screening electrocardiogram (ECG) (using the QTcF formula)\r\n* Angina pectoris that requires the use of anti-anginal medication\r\n* Ventricular arrhythmias except for benign premature ventricular contractions\r\n* Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication\r\n* Conduction abnormality requiring a pacemaker\r\n* Valvular disease with document compromise in cardiac function\r\n* Symptomatic pericarditis
+Patients with known serious cardiac illness or medical conditions, including but not limited to:\r\n* Clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, unstable angina or history of myocardial infarct within 6 months prior to enrollment, or indwelling temporary pacemaker\r\n* Ventricular tachycardia or a supraventricular tachycardia that requires treatment with antiarrhythmic agents\r\n* Second- or third-degree atrioventricular block unless treated with a permanent pacemaker\r\n* Complete left bundle branch block\r\n* History of long QT syndrome or a family member with this condition
+Evidence of active heart disease within the 3 months prior to study entry; symptomatic coronary insufficiency or heart block; congestive heart failure; moderate or severe pulmonary dysfunction, torsades de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia, heart block, or congenital long QT syndrome
+Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%, testing is required in patients with:\r\n* Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block\r\n* Age >= 60 years old
+Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%; testing is required in patients with:\r\n* Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block\r\n* Age >= 60 years old
+Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting [CABG], coronary angioplasty, or stenting) < 6 months prior to screening\r\n* Symptomatic chronic heart failure\r\n* Evidence of clinically significant cardiac arrhythmias and/or conduction abnormalities < 6 months prior to screening except atrial fibrillation and paroxysmal supraventricular tachycardia
+Patients with New York Health Association (NYHA) class III and IV heart failure, myocardial infarction in the preceding 6 months, and conduction abnormalities, including but not limited to atrial fibrillation, atrioventricular (AV) block, QT prolongation, sick sinus syndrome, ventricular tachycardia
+History of myocardial infarction =< 168 days (6 months), or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
+Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at Screening has to be documented by the investigator as not medically relevant
+SELUMETINIB ARM: Cardiac conditions as follows:\r\n* Uncontrolled hypertension (blood pressure [BP] >= 150/95 despite optimal therapy)\r\n* Heart failure NYHA class II or above\r\n* Prior or current cardiomyopathy\r\n* Baseline left ventricular ejection fraction (LVEF) =< 50%\r\n* Atrial fibrillation with heart rate > 100 bpm\r\n* Unstable ischemic heart disease (myocardial infarction [MI] within 6 months prior to starting treatment, or angina requiring use of nitrates more than once weekly)
+Documented left ventricular ejection fraction (LVEF) of less than 45% tested in patients with:\r\n* History of ischemic heart disease, chest pain, or clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block\r\n* Age greater than or equal to 60 years old
+NON-PROGRESSED DIPG (STRATUM 2): Patient has no ventricular arrhythmias except for benign premature ventricular contractions
+Persistent or uncontrolled ventricular arrhythmias or atrial fibrillation.
+Any history of ventricular fibrillation or torsade de pointes
+Patient had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiography (ECG) abnormality at screening must be documented by the investigator as not medically relevant
+History of myocardial infarction =< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
+Any history of ventricular fibrillation or torsade de pointes.
+Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure (New York Heart Association [NYHA) class III or IV), unstable angina pectoris, myocardial infarction within 6 months prior to enrollment, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
+Documented left ventricular ejection fraction (LVEF) of less than or equal to 45% tested; the following patients will undergo cardiac evaluations\r\n* Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or\r\n* Age >= 60 years old
+Known history of severe and/or uncontrolled ventricular arrhythmias
+Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
+History of torsade de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia (<60 bpm), heart block (excluding 1st degree block, being PR interval prolongation only), congenital long QT syndrome or new ST segment elevation or depression or new Q wave on ECG
+Arrhythmia (example, history of polymorphic ventricular fibrillation or torsade de pointes). However, participants with < Grade 3 atrial fibrillation for a period of at least 6 months may enroll. Grade 3 atrial fibrillation is defined as symptomatic and incompletely controlled medically, or controlled with device (example, pacemaker) or ablation, and is excluded. Participants with paroxysmal atrial fibrillation are permitted to enroll.
+Impaired 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)
+Patient had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
+A history or evidence of cardiovascular risk including any of the following: A QT interval corrected for heart rate using the Fridericia's formula (QTcF) >=480 millisecond (msec); A history or evidence of current clinically significant uncontrolled arrhythmias; Exception: Subjects with atrial fibrillation controlled for >30 days prior to Study Day 1 (Parts 1 and 2) or randomization (Part 3); History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to Study Day 1 (Parts 1 and 2) or randomization (Part 3); A history or evidence of current >=Class II congestive heart failure as defined by the New York Heart Association (NYHA) guidelines; Treatment refractory hypertension defined as a blood pressure of systolic>140 millimeters of mercury (mmHg) and/or diastolic >90 mmHg which cannot be controlled by anti-hypertensive therapy; Patients with intra-cardiac defibrillators or permanent pacemakers; Known cardiac metastases.
+History of clinically significant cardiac dysfunction, including: \r\n* Unstable angina\r\n* Unstable atrial fibrillation\r\n* Symptomatic bradycardia\r\n* Indwelling temporary pacemaker\r\n* History of myocardial infarction (MI) within 6 months prior to first study treatment\r\n* History of symptomatic congestive heart failure (CHF) (grade > 3 by NCI CTCAE or class > II by New York Heart Association [NYHA] criteria)\r\n* Ventricular tachycardia or a supraventricular tachycardia that requires treatment with a class 1a antiarrhythmic drug (e.g. quinidine, procainamide, disopyramide) or class III antiarrhythmic drug (e.g. sotalol, amiodarone, dofetilide); use of other antiarrhythmic drugs is permitted\r\n* Second or third degree atrioventricular (AV) block unless treated with a permanent pacemaker\r\n* Complete left bundle branch block (LBBB)\r\n* History of long QT syndrome or a family member with this condition
+Current, serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute arrhythmia or ventricular arrhythmias classified as Lown III, IV or V.
+Evidence of poor cardiovascular function defined as b-type natriuretic peptide (BNP) > 100 pg/mL, or history of congestive heart failure, unstable angina, uncontrolled hypertension, or clinically significant ventricular arrhythmias at screening;
+Inclusion Criteria:\n\n        Diagnosis of intermediate- or high-risk (IPSS criteria) myelodysplastic syndrome.\n\n        Cohort 1: Any prior treatment, enrollment complete. Cohort 2: Limited or no prior treatment\n        for MDS. Prior treatment should not include hypomethylating agents such as azacitidine or\n        decitabine, or HDAC inhibitors.\n\n        ECOG Performance Status 0 or 1.\n\n        Exclusion Criteria:\n\n        Current or history of small, moderate or large pericardial effusion, tamponade and/or\n        pericarditis.\n\n        Significant cardiac abnormalities such as recent myocardial infarction, congestive heart\n        failure ? Class 3, or symptomatic, uncontrolled atrial fibrillation, atrial flutter or\n        sinus tachycardia.\n\n        Prolonged QT/QTc interval.\n\n        Other active cancer excluding basal cell carcinoma or cervical intraepithelial neoplasia.
+Significant cardiovascular disease including:\r\n* Active, clinically symptomatic left ventricular failure\r\n* Uncontrolled symptomatic hypertension that cannot be controlled with anti-hypertensive agents\r\n* Myocardial infarction, severe angina, or unstable angina within 6 months prior to administration of first dose of study drug\r\n* History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) \r\n* Cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication)  \r\n* Coronary or peripheral artery bypass graft within 6 months of screening
+History or evidence of cardiovascular risk including any of the following:\r\n* Left ventricular ejection fraction (LVEF) < LLN\r\n* A QT interval corrected for heart rate using the Bazett’s formula QTcB >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization\r\n* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Patients with intra-cardiac defibrillators\r\n* Known cardiac metastases
+History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation)
+Other significant electrocardiogram (EKG) abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min)
+A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), torsade de pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD)
+Patient had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
+The following cardiac abnormalities: Corrected QT (QTc) interval >=480 millisecond. History of acute coronary syndromes (including unstable angina) within the past 24 weeks Coronary angioplasty or stenting within the past 24 weeks. Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system. Abnormal cardiac valve morphology (>= Grade 2) documented by echocardiogram (subjects with Grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study). History of known arrhythmias (except sinus arrhythmia and atrial fibrillation that is controlled) within the past 24 weeks.
+Active congestive heart failure or ventricular arrhythmia
+Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities (except asymptomatic patients with a pacemaker with electrocardiogram (ECG) changes reflecting conduction abnormalities secondary to the pacemaker); prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant
+Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
+Unstable atrial fibrillation (ventricular response >100 bpm)
+Unstable angina or myocardial infarction within 4 months prior to randomization, New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or grade 3 conduction system abnormalities unless subject has a pacemaker
+Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
+Any of the following conditions:\r\n* Myocardial infarction =< 6 months prior to registration or has New York Heart Association (NYHA) class III or IV heart failure \r\n* Uncontrolled angina\r\n* Severe uncontrolled ventricular arrhythmias\r\n* Electrocardiographic evidence of acute ischemia\r\n* Active conduction system abnormalities; NOTE: prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
+Active cardiac disease including any of the following:\r\n* History of left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* Frederica corrected QT interval (QTcF) > 450 msec on screening electrocardiogram (ECG)\r\n* Angina pectoris that requires the use of anti-anginal medication\r\n* History of ventricular arrhythmias except for benign premature ventricular contractions\r\n* Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication\r\n* Conduction abnormality requiring a pacemaker\r\n* Valvular disease with documented compromise in cardiac function\r\n* Symptomatic pericarditis
+Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:\r\n* History or presence of sustained ventricular tachyarrhythmia; (patients with a history of atrial arrhythmia are eligible but should be discussed with Novartis prior to enrollment)\r\n* Any history of ventricular fibrillation or torsade de pointes\r\n* Bradycardia defined as heart rate (HR) < 50 beats per minute (bpm); patients with pacemakers are eligible if resting HR >= 50 bpm\r\n* Screening electrocardiogram (ECG) with a corrected QT with Fridericia's formula (QTcF) > 480 msec\r\n* Right bundle branch block + left anterior hemiblock (bifascicular block)\r\n* Patients with myocardial infarction or unstable angina =< 6 months prior to starting study drug\r\n* Other clinically significant heart disease (e.g., congestive heart failure [CHF] New York [NY] Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
+History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsade de pointes)
+Abnormal 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.
+History or evidence of cardiovascular risk including any of the following: Clinically significant electrocardiogram abnormalities including second degree (Type II) or third degree atrioventricular block; history of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, stenting, or bypass grafting within the past 6 months prior to enrolment, Class III or IV heart failure as defined by the New York Heart Association functional classification system, LVEF below 50%; known cardiac metastases
+A history or evidence of cardiovascular risk including: a QT interval corrected for heart rate using the Bazett's formula (QTcB) >=480 msec; a history or evidence of current clinically significant uncontrolled arrhythmias (clarification: Subjects with atrial fibrillation controlled for >30 days prior to dosing are eligible); a history of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization; a history or evidence of current >=Class II congestive heart failure as defined by the New York Heart Association (NYHA) guidelines; subjects with intra-cardiac defibrillators; abnormal cardiac valve morphology (>=grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study). Subjects with moderate valvular thickening should not be entered on study. Subjects with prosthetic valves can be considered eligible provided they meet the criteria as stated above; Treatment refractory hypertension defined as a blood pressure of systolic >140 millimeter of mercury (mmHg) and/or diastolic >90 mmHg (or above 95th age-specific percentile listed in protocol), which cannot be controlled by anti-hypertensive therapy.
+Clinically significant cardiac dysfunction (including NYHA Class II/III/IV heart failure, left ventricular ejection fraction [LVEF] <50%, active ventricular arrhythmia requiring medication, history of myocardial infarction within 6 months of treatment initiation, clinically significant electrocardiogram [ECG] abnormalities).
+Documented LVEF of less than or equal to 45% tested in patients with i) clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or ii) age >= 60 years old
+Uncontrolled angina or uncontrolled hypertension or any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
+High-risk uncontrolled arrhythmias (ventricular tachycardia, high-grade atrioventricular [AV]-block, supra-ventricular arrhythmias which are not adequately rate-controlled) that require current treatment with the following anti-arrhythmic drugs: flecainide, moricizine or propafenone
+History of myocardial infarction (MI) or NYHA Class II-IV congestive heart failure within 6 months of the administration of the first dose of ARQ 092 (MI occurring >6 months of the first dose of ARQ 092 will be permitted); Grade 2 or worse conduction defect (eg right or left bundle branch block); left ventricular ejection fraction (LVEF) < 50% assessed by echocardiogram/MUGA scan
+Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:\r\n* History or presence of sustained ventricular tachyarrhythmia; (patients with a history of atrial arrhythmia are eligible but should be discussed with Novartis prior to enrollment)\r\n* Any history of ventricular fibrillation or torsade de pointes\r\n* Bradycardia defined as heart rate (HR) < 50 beats per minute (bpm); patients with pacemakers are eligible if HR >= 50 bpm\r\n* Screening electrocardiogram (ECG) with a QTc > 450 msec\r\n* Right bundle branch block + left anterior hemiblock (bifascicular block)\r\n* Patients with myocardial infarction or unstable angina =< 6 months prior to starting study drug\r\n* Other clinically significant heart disease (e.g., congestive heart failure [CHF] New York [NY] Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
+Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
+Donor must have adequate cardiac function with no history of congestive heart failure and no history of atrial fibrillation or ventricular tachyarrhythmia.
+Recent history of ischemic heart disease, electrocardiogram (ECG) abnormalities, or atrial fibrillation.
+Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
+Myocardial infarct within 6 months before enrollment, New York Heart Association Class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities
+Any of the following concurrent severe and/or uncontrolled medical conditions that could compromise participation in the study: \r\n* ST depression or elevation of >= 1.5 mm in 2 or more leads\r\n* Congenital long QT syndrome\r\n* History or presence of sustained ventricular arrhythmias or atrial fibrillation\r\n* Clinically significant resting bradycardia (< 50 beats per minutes)\r\n* Corrected QT interval (QTc) > 480 msec on screening electrocardiogram (ECG)\r\n* Complete left bundle branch block\r\n* Right bundle branch block + left anterior hemiblock (bifascicular block)\r\n* Unstable angina pectoris =< 6 months prior to starting study drug\r\n* Acute myocardial infarction =< 6 months prior to starting study drug\r\n* Other clinically significant heart disease such as congestive heart failure requiring treatment (New York Heart Association [NYHA] class III or IV) or uncontrolled hypertension (please refer to World Health Organization [WHO]-International Society of Hypertension [ISH] guidelines)
+Patients with a history of syncope, family history of idiopathic sudden death, a history of sustained or clinically significant cardiac arrhythmias, symptomatic congestive heart failure (New York Heart Association [NYHA] class III or IV), unstable angina pectoris, sustained ventricular tachycardia, ventricular fibrillation, advanced heart block, or a history of acute myocardial infarction within the six months preceding enrollment
+Compromised cardiovascular function defined as any of the following:\r\n* Electrocardiogram (EKG) evidence of acute ischemia\r\n* EKG evidence of medically significant conduction system abnormalities\r\n* History of myocardial infarction within the last 6 months\r\n* Unstable angina pectoris or cardiac arrhythmia\r\n* History of class 3 or class 4 New York Heart Association congestive heart failure\r\n* Left ventricular ejection fraction (LVEF) < 55% by either echocardiography or radionuclide-based multiple gated acquisition (Echo or MUGA)
+History of arrhythmia (multifocal premature ventricular contractions PVCs), bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia; atrial fibrillation, controlled on medication, is not excluded
+Presence of unstable atrial fibrillation (ventricular response > 100 bpm
+Impaired cardiac function or clinically significant cardiac diseases, including any one of the following: history or presence of sustained ventricular tachyarrhythmia; any history of ventricular fibrillation or torsade de pointes; bradycardia defined as heart rate (HR) < 50 beats per minute (bpm); patients with pacemakers are eligible if HR >= 50 bpm; screening electrocardiogram (ECG) with a corrected QT interval (QTc) > 450 msec; right bundle branch block + left anterior hemiblock (bifascicular block); patients with myocardial infarction or unstable angina =< 6 months prior to starting study drug; other clinically significant heart disease (e.g., congestive heart failure [CHF] New York [NY] Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
+Myocardial infarction within 4 months prior to randomization, NYHA Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker
+Active ventricular arrhythmia requiring medication
+New York Heart Association (NYHA) Class III or IV heart failure, arrhythmias or unstable angina, electrocardiograph (ECG) evidence of active ischemia or active conduction system abnormalities, or myocardial infarction within the last 6 months (prior to study entry, ECG abnormalities at screening must be documented by the investigator as not medically relevant)
+History of myocardial infarction =< 6 months from registration, or congestive heart failure requiring use of ongoing maintenance therapy for life threatening ventricular arrhythmias
+Patients meeting the following criteria are not eligible: history of unstable angina, myocardial infarction, transient ischemic attack (TIA), stroke, peripheral arterial occlusive disease, venous thromboembolism or pulmonary embolism; any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes); prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (> 470 msec) on both the Fridericia and Bazett’s correction; symptomatic congestive heart failure within 3 months prior to first dose of ponatinib (New York Heart Association [NYHA] class III or IV)
+History of any of the following within the last 6 months before administration of the first dose of the drug:\r\n* Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures,\r\n* Ischemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures,\r\n* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia),\r\n* Placement of a pacemaker for control of rhythm,\r\n* New York Heart Association (NYHA) class III or IV heart failure, -Pulmonary embolism
+History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
+Uncontrolled intercurrent illness including, but not limited to,\r\n* Ongoing or active infection\r\n* Psychiatric illness/social situations that would limit compliance with study requirements\r\n* Clinically significant cardiac disease including any of the following:\r\n** Congestive heart failure requiring treatment (New York Heart Association grade >= 2), left ventricular ejection fraction (LVEF) < 50% as determined by multi gated acquisition scan (MUGA) scan or echocardiogram\r\n** Uncontrolled hypertension (defined as systolic blood pressure [BP] >= 160 mmHg OR diastolic BP >= 100 mmHg despite maximal anti-hypertensive medications: refer to World Health Organization [WHO]-International Society of Hypertension [ISH] guidelines)\r\n** History or presence of clinically significant ventricular arrhythmias, atrial fibrillation, resting bradycardia, or conduction abnormality\r\n** Unstable angina pectoris or acute myocardial infarction < 3 months prior to starting study treatment\r\n** Corrected QT using the Fredericia's formula (QTcF) > 450 msec (males); > 470 msec (females)\r\n** History of congenital long QT syndrome
+Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%, testing is required in patients with:\r\n* Age >= 60 years old\r\n* Clinically significant atrial and or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block
+Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, (third-degree atrioventricular [AV] block, ventricular tachycardia, atrial fibrillation with rapid ventricular rate [heart rate (HR) > 100 beats per minute (bpm)]),congestive heart failure, or myocardial infarction within 2 months of screening, or any class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
+Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%; testing is required in patients with:\r\n* Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block\r\n* Age >= 60 years old
+Myocardial infarction or unstable angina within 6 months prior to enrollment or has New York Hospital Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities\r\n* Fridericia corrected QT interval (QTcF) > 470 msec on the screening of electrocardiogram (ECG) (as mean of triplicate ECGs)
+New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
+Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) < 6 months prior to screening,\r\n* Symptomatic chronic heart failure, history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality < 6 months prior to screening except atrial fibrillation and paroxysmal supraventricular tachycardia
+Impaired cardiac function or clinically significant cardiac diseases, including any of the following:\r\n* History or presence of serious uncontrolled ventricular arrhythmias\r\n* Clinically significant resting bradycardia\r\n* Ongoing cardiac dysrhythmias, atrial fibrillation, or prolongation of corrected QTc interval to > 480 msec\r\n•\t* Left ventricular ejection fraction (LVEF) assessed by 2-dimensional (2-D) echocardiogram (ECHO) < 50% or lower limit of normal (whichever is the higher), or 2-D multiple gated acquisition scan (MUGA) < 45% or lower limit of normal (whichever is the higher)\r\n* Any of the following =< 180 days prior to starting study drug: myocardial infarction (MI), severe/unstable angina, coronary artery bypass graft (CABG), congestive heart failure (CHF), cerebrovascular accident (CVA), transient ischemic attack (TIA)\r\n* Uncontrolled hypertension defined by a systolic blood pressure (SBP) >= 160 mm Hg and/or diastolic (D)BP >= 100 mm Hg, with or without anti-hypertensive medication(s); initiation or adjustment of antihypertensive medication(s) is allowed prior to study entry
+A history or evidence of cardiovascular risk including any of the following:\r\n* A corrected QT (QTc) interval >= 500 ms at screening\r\n* A history or evidence of current clinically significant uncontrolled arrhythmias\r\n** Exception: Subjects with atrial fibrillation controlled for > 30 days prior to randomization are eligible\r\n* A history (within 6 months prior to randomization) of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty\r\n* A history or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) guidelines\r\n* Treatment refractory hypertension defined as a blood pressure of systolic > 150 mmHg and/or diastolic > 100 mm Hg which cannot be controlled by antihypertensive therapy\r\n* Patients with intra-cardiac defibrillators or permanent pacemakers
+Patient has any of the following cardiac abnormalities:\r\n* Symptomatic congestive heart failure\r\n** History of documented congestive heart failure (New York Heart Association functional classification III-IV), documented cardiomyopathy\r\n** Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* Myocardial infarction =< 6 months prior to enrollment\r\n* Unstable angina pectoris\r\n* Serious uncontrolled cardiac arrhythmia\r\n* Symptomatic pericarditis\r\n* Corrected QT interval using Fridericia's formula (QTcF) > 480 msec on the screening electrocardiogram (ECG) (using the QTcF formula)\r\n* Currently receiving treatment with medication that has a known risk to prolong the QT interval or inducing Torsades de Pointes, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug
+Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes [TdP]);
+Patients with sick-sinus syndrome, sino-atrial block, third degree heart block, atrial fibrillation, and those with permanent pacemakers
+Significant cardiovascular disease, including:\r\n* Symptomatic left ventricular dysfunction or known baseline left ventricular ejection fraction (LVEF) by multigated acquisition scan (MUGA) or echocardiogram (ECHO) of < lower limit of institutional normal (LLN); \symptomatic\ is defined as New York Heart Association (NYHA) class II or greater; Note: MUGA and ECHO do not need to be measured to establish eligibility for this study\r\n* Uncontrolled hypertension (in the opinion of the treating provider)\r\n* Myocardial infarction, severe angina, or unstable angina within 6 months prior to administration of first dose of study drug\r\n* History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) within 12 months of first dose of study drug\r\n* Uncontrolled cardiac arrhythmias\r\n* Coronary or peripheral artery bypass graft within 6 months of first dose of study drug\r\n* History of cerebrovascular accident (CVA), transient ischemic attack (TIA), or rest claudication within 6 months of first dose of study drug
+Patients who have a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological original (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest
+Patients who have had a myocardial infarction within 6 months of enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
+Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
+History of or active ventricular dysrhythmias or congestive heart failure requiring medication or symptomatic coronary heart disease
+Evidence of current, uncontrolled cardiovascular conditions including cardiac arrhythmias, angina, pulmonary hypertension, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
+Clinically significant cardiovascular disease within 6 months of study treatment including:\r\n* Severe or unstable angina\r\n* Myocardial infarction\r\n* Symptomatic congestive heart failure\r\n* New York Heart Association (NYHA) (class II-IV heart disease)\r\n* Arterial or venous thromboembolic events (such as pulmonary embolism cerebrovascular accident including transient ischemic attacks)\r\n* History of clinically significant ventricular arrhythmias (e.g. ventricular tachycardia, ventricular fibrillation, torsades de pointes)\r\n* Prolonged corrected QT interval by the Fridericia correction formula (QTcF) on screening electrocardiogram (EKG) > 470 msec\r\n* History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place\r\n* Uncontrolled hypertension (systolic blood pressure >= 140 mmHg or diastolic blood pressure >= 90 mmHg); participants with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive therapy
+Uncontrolled tachy or bradyarrhythmia or active myocardial ischemia defined as either: atrial fibrillation with rapid ventricular response (heart rate [HR] > 120 beats per minute [bpm]), ventricular tachycardia or nonsustained ventricular tachycardia, supraventricular tachycardia, third degree heart block, any heart rate less than 40 bpm
+History of myocardial infarction =< 180 days prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmia
+Sustained or symptomatic ventricular dysrhythmias uncontrolled with drug therapy or implantable device; significant conduction defects (i.e.: second or third degree atrio-ventricular block or sick sinus syndrome)
+History of clinically relevant ventricular arrhythmias (eg, ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes);
+Clinically significant cardiovascular disease including:\r\n* Myocardial infarction within six months prior to screening\r\n* Uncontrolled angina within three months prior to screening\r\n* Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subjects with history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multigated acquisition (MUGA) scan performed within 3 months results in a left ventricular ejection fraction that is >= 45%\r\n* History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes)\r\n* History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place
+Significant active cardiovascular or pulmonary disease including:\r\n* Uncontrolled hypertension (i.e., systolic blood pressure > 180 mmHg, diastolic blood pressure > 95 mmHg); use of anti-hypertensive agents to control hypertension before cycle 1 day 1 is allowed\r\n* Pulmonary hypertension\r\n* Uncontrolled asthma or oxygen (O2) saturation < 90% by arterial blood gas analysis or pulse oximetry on room air\r\n* Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement\r\n* History of arrhythmia requiring an implantable cardiac defibrillator\r\n* Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiogram (ECG) e.g. medically significant (symptomatic) bradycardia, complete left bundle branch block, third degree heart block and second-degree heart block or history of arrhythmia requiring an implantable cardiac defibrillator; or within the last 6 months before administration of the first dose of drug:\r\n** Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)\r\n** Placement of a pacemaker for control of rhythm\r\n** Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures\r\n** Ischemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures\r\n** New York Heart Association (NYHA) class III or IV heart failure\r\n** Pulmonary embolism\r\n* Baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTcF >= 470 msec (mean value) obtained from 3 ECGs, using the screening clinic ECG machine derived QTc value, or history of congenital long QT syndrome, or torsades de pointes); any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval\r\n* Left ventricular ejection fraction (LVEF) by either multigated acquisition (MUGA) or echocardiography (ECHO) less than lower limit of normal
+Unstable cardiovascular function: symptomatic ischemia (chest pain of cardiac origin), or uncontrolled clinically significant conduction abnormalities (e.g. ventricular tachycardia on antiarrhythmics are excluded and 1st degree atrioventricular [AV] block or asymptomatic left anterior fascicular block [LAFB]/right bundle branch block [RBBB] will not be excluded), or congestive heart failure (CHF) of New York Heart Association (NYHA) class >= 3, or myocardial infarction (MI) within 3 months of consent date
+History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
+No myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
+Patient had myocardial infarction within 6 months prior to enrollment, New York Hospital Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
+Any known cardiac abnormalities such as:\r\n* Congenital long QT syndrome\r\n* QTc interval >= 480 milliseconds;\r\n* Myocardial infarction within 6 months of course 1, day 1 (C1D1); subjects with a history of myocardial infarction between 6 and 12 months prior to C1D1 who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event may participate;\r\n* Other significant electrocardiogram (ECG) abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min);\r\n* Symptomatic coronary artery disease (CAD), e.g., angina Canadian class II-IV; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;\r\n* An ECG recorded at screening showing evidence of cardiac ischemia (ST depression of >= 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;\r\n* Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II to IV definitions and/or ejection fraction < 40% by multi gated acquisition (MUGA) scan or < 50% by echocardiogram and/or magnetic resonance imaging (MRI);\r\n* A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD);\r\n* Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other cause;\r\n* Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)
+Significant conduction defects (i.e. second or third degree atrio-ventricular block or sick sinus syndrome)
+Any history of ventricular fibrillation or torsades de pointes
+Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiography (ECG) abnormality at screening must be documented by the investigator as not medically relevant
+Class II or greater New York Heart Association Functional Classification criteria or serious cardiac arrhythmias likely to increase the risk of cardiac complications of cytokine therapy (e.g. ventricular tachycardia, frequent ventricular ectopy, or supraventricular tachyarrhythmia requiring chronic therapy)
+Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:\r\n* Any history of ventricular fibrillation or torsade de pointes\r\n* Bradycardia defined as heart rate (HR) < 45 beats per minute (bpm); patients with pacemakers are eligible if HR >= 45 bpm\r\n* Screening electrocardiogram with a QT corrected for Fridericia's formula (QTcF) >= 480 msec\r\n* Right bundle branch block + left anterior hemiblock (bifascicular block)\r\n* Patients with myocardial infarction or unstable angina =< 12 months prior to starting study drug\r\n* Other clinically significant heart disease (e.g., Classification of Heart failure [CHF] New York Heart Association class III or IV, uncontrolled hypertension) as per discretion of principal investigator and/or treating physician\r\n* Patients using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug with the exception of drugs that are required for hematopoietic cell transplantation (HCT) patients
+Patients with a history of arrhythmia or asymptomatic sustained ventricular tachycardia are not eligible. Patients with atrial fibrillation with well-controlled ventricular rate on medication, are eligible.
+Significant ventricular arrhythmias (> 20 premature ventricular contractions [PVCs]/min due to gating difficulty) atrial fibrillation with uncontrolled ventricular response
+Patients with a history of any of the following within the last 6 months prior to study entry are ineligible:\r\n* Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures\r\n* Ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures\r\n* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)\r\n* Placement of a pacemaker for control of rhythm\r\n* New York Heart Association (NYHA) class III or IV heart failure\r\n* Pulmonary embolism
+Evidence of cardiovascular risk including any of the following: QT interval corrected>=470 millisecond, evidence of current clinically significant uncontrolled arrhythmias, history of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within six months of Screening, Class III or IV heart failure as defined by the New York Heart Association functional classification system, uncontrolled hypertension, subjects with intra-cardiac defibrillators or permanent pacemakers, abnormal cardiac valve morphology (>=grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study). Subjects with moderate valvular thickening should not be entered on study.
+History or evidence of cardiovascular risk including any of the following:\r\n* Left ventricular ejection fraction (LVEF) < LLN\r\n* A QT interval corrected for heart rate using the Bazett’s formula corrected QT (QTcB) >= 480 msec\r\n* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to registration are eligible)\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to registration\r\n* History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system\r\n* Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy\r\n* Known cardiac metastases
+Have current or a history of ventricular or life-threatening arrhythmias or diagnosis
+History of arrhythmia (multifocal premature ventricular contractions [PVCs], bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation), which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia; atrial fibrillation, controlled on medication is not excluded
+Cardiac dysrhythmia that is potentially life-threatening, such as ventricular tachycardia, multifocal premature ventricular contractions or supraventricular tachycardias with a rapid ventricular response; well-controlled atrial fibrillation or rare (< 2 minute) premature ventricular contractions are not exclusionary
+History of coronary artery disease, including myocardial infarction, congestive heart failure (left ventricular [LV] ejection fraction < 50% or clinically significant diastolic dysfunction), or any serious medical condition which would preclude a patient from undergoing a bronchoscopy or would jeopardize the goals of the study
+Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiography (ECG) abnormality at screening must be documented by the investigator as not medically relevant
+Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) Class III or IV heart failure (see Appendix D), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant.
+In addition, subjects with any contraindications to exercise testing according to American Heart Association guidelines will not be enrolled; nonetheless, the cardiovascular magnetic resonance (CMR) cardiologist supervising the research portion of the exam will also evaluate each subject for evidence of any contra-indications; the absolute contra-indications include acute myocardial infarction, high-risk unstable angina, uncontrolled cardiac arrhythmias, active endocarditis, symptomatic severe aortic stenosis, decompensated symptomatic heart failure, acute pulmonary embolus or pulmonary infarction, acute non-cardiac disorder that may be aggravated by exercise, acute myocarditis or pericarditis, physical disability that would preclude safe and adequate test performance, and inability to provide consent; the relative contra-indications include left main coronary stenosis, moderate stenotic valvular heart disease, electrolyte abnormalities, tachyarrhythmias or bradyarrhythmias, atrial fibrillation with uncontrolled ventricular rate, hypertrophic cardiomyopathy, and high-degree atrioventricular node block; subjects with uncontrolled hypertension and resting blood pressure exceeding 140/80 mmHg will be excluded
+Active cardiac disease including any of the following:\r\n* Severe congestive heart failure (class IV in accordance with the classification of the New York Heart Association)\r\n* Unstable angina\r\n* Severe arrhythmia (i.e. ventricular tachycardia, flutter fibrillation; ventricular premature complexes occurring close to the preceding T-wave, multifocal complexes)\r\n* Myocardial infarction within 1 year prior to the date of proposed Definity administration\r\n* Uncontrolled systemic hypertension (systolic blood pressure [BP] > 150 mmHg and/or diastolic BP > 90 mmHg despite optimal medical management)
+Significant ventricular arrhythmias (> 20 premature ventricular contractions [PVCs]/minute due to gating difficulty)
+Atrial fibrillation with uncontrolled ventricular response
+Has any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiogram (ECG), eg, complete left bundle branch block, third-degree heart block, second-degree heart block, or PR interval > 250 milliseconds (ms)
+Uncontrolled clinically significant conduction abnormalities (e.g., patients with ventricular tachycardia on anti-arrhythmics are excluded; patients with first-degree atrioventricular block or asymptomatic left anterior fascicular block/right bundle branch block will not be excluded), or
+Patients who have experienced any of the following procedures or conditions currently or in the preceding 12 months:\r\n* Coronary artery bypass graft\r\n* Angioplasty\r\n* Vascular stent\r\n* Myocardial infarction\r\n* Angina pectoris\r\n* Congestive heart failure New York Heart Association grade >= 2 (ventricular arrhythmias requiring continuous therapy)\r\n* Supraventricular arrhythmias including atrial fibrillation, which are uncontrolled\r\n* Hemorrhagic or thrombotic stroke, including transient ischemic attacks or any other central nervous system bleeding\r\n* History of drug abuse or alcohol abuse, as judged by the investigator
+Any one of the following currently or in the previous 3 months: myocardial infarction, congenital long QT syndrome, torsades de pointes, uncontrolled arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), right bundle branch block and left anterior fascicular hemiblock (bifascicular block), unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (congestive heart failure [CHF] New York [NY] Heart Association classification III or IV) , cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism not adequate medically managed with anticoagulants, ongoing cardiac dysrhythmias of CTCAE grade >= 2, symptomatic atrial fibrillation of any grade, corrected QT (QTc) interval >= 481 msec at screening
+Subject has uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia, congestive heart failure New York Heart Association (NYHA) class 3 or 4 or subject has a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multigated acquisition (MUGA) scan performed within 1 month prior to study entry results in a left ventricular ejection fraction that is ? 45%.
+Patients with clinically unstable cardiac arrhythmias, such as recurrent ventricular tachycardia
+Acute heart disease or history of heart attack, atrial fibrillation, or angina
+Electrocardiogram (ECG) demonstrating clinically significant arrhythmias; subjects with chronic atrial\r\narrhythmia, (i.e., atrial fibrillation or paroxysmal supraventricular tachycardia), are eligible
+Myocardial infarct within 6 months before enrollment, New York Heart Association (NYHA) class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
+Clinically significant cardiovascular disease including:\r\n* GROUP 2 (trametinib arm): LVEF < LLN\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months\r\n* Uncontrolled angina within 3 months\r\n* GROUP 1 and GROUP 3 (non-trametinib arms): Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or patients with history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multi-gated acquisition scan performed within 3 months results in a left ventricular ejection fraction that is >= 45%\r\n* GROUP 2 (trametinib arm): Any history of congestive heart failure of any NYHA class for patients assigned to Group 2 (trametinib arm)\r\n* History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes)\r\n* Patients with intra-cardiac defibrillators or permanent pacemakers\r\n* Hypotension as indicated by systolic blood pressure < 86 millimeters of mercury (mmHg) at the screening visit\r\n* Bradycardia as indicated by a heart rate of < 40 beats per minute on the screening electrocardiogram (ECG)\r\n* Treatment refractory hypertension defined as a blood pressure of systolic > 160 mmHG and/or diastolic > 95 mmHG which cannot be controlled by anti-hypertensive therapy\r\n* Corrected QT interval (QTC) >= 480 milliseconds\r\n* Known cardiac metastases
+Have documented major electrocardiogram (ECG) abnormalities (not responding to medical treatments) at the investigator's discretion (for example, symptomatic or sustained atrial or ventricular arrhythmias, second- or third-degree atrioventricular block, complete bundle branch block, ventricular hypertrophy, or recent myocardial infarction).
+History or evidence of cardiovascular risk including any of the following:\r\n* Corrected QT (QTc) interval >= 480 msecs\r\n* Clinically significant uncontrolled arrhythmias; exception: subjects with controlled atrial fibrillation for > 30 days prior to day 1 of treatment with GSK1120212 are eligible\r\n* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within the past 24 weeks\r\n* >= class II heart failure as defined by the New York Heart Association (NYHA) functional classification system
+With the exception of treatment-naïve elderly AML patients, patients with uncontrolled congestive heart failure (CHF), coronary heart disease (CAD), chronic obstructive pulmonary disease (COPD), or left ventricular ejection fraction (LVEF) of ? 50% are excluded, symptomatic or uncontrolled arrhythmias or on continuous corticosteroids.
+Evidence of current uncontrolled cardiovascular conditions including cardiac arrhythmias, angina, pulmonary hypertension, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
+Have a personal history of any of the following conditions: syncope of either unexplained or cardiovascular etiology, ventricular arrhythmia (including but not limited to ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest. Exception: subjects with controlled atrial fibrillation for >30 days prior to study treatment are eligible.
+Significant medical comorbidities, including uncontrolled hypertension (diastolic blood pressure >115 mm Hg), unstable angina, congestive heart failure (greater than New York Heart Association class II), severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia, poorly controlled diabetes, severe chronic pulmonary disease, coronary angioplasty, myocardial infarction within 6 months prior to Screening, or uncontrolled atrial or ventricular cardiac arrhythmias.