Myocardial infarction or arterial thrombotic event within 6 months, heart failure of New York Heart Association class II or higher, uncontrolled angina, severe uncontrolled ventricular arrhythmia
Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association > class II) within 12 months of first dose of AMG 757
Patients with active heart disease (New York Heart Association [NYHA] class 3-4 as assessed by history and physical examination, unstable angina/stroke/myocardial infarction within the last 6 months)
History of symptomatic congestive heart failure ([CHF]; New York Heart Association [NYHA] Classes II-IV), ventricular arrhythmia requiring treatment, current unstable angina, or history of myocardial infarction within 6 months prior to study entry
Clinically significant cardiac dysfunction defined as a history of >= New York Heart Association (NYHA) class II symptoms, angina, congestive heart failure, myocardial infarction, arrhythmias or cardiac dysfunction requiring treatment or discontinuation of chemotherapy
Have a history of New York Heart Association (NYHA) Class ?3, unstable angina, or myocardial infarction (MI) in 6 months prior to study drug administration
Myocardial infarction within 6 months before starting therapy, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication.
Subject has a history of a major adverse cardiac event, including cerebrovascular accident or myocardial infarction within the prior 6 months, or uncontrolled congestive heart failure (New York Heart Association class 3 or 4) at Screening.
Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association > class II) within 12 months of enrollment.
Unstable angina, new-onset angina within last 3 months, myocardial infarction within the last 6 months prior to Day 1 of Cycle 1, or current congestive heart failure classified as New York Heart Association Class II or higher
Cardiac conditions: congestive heart failure, New York Heart Association class 3-4 heart failure, baseline left ventricular ejection fraction (LVEF) < 50%, transmural myocardial infarction, uncontrolled hypertension, angina pectoris requiring medication, clinically significant valvular disease, high-risk arrhythmia in the past 12 months
History of myocardial infarction or stroke within 6 months, congestive heart failure greater than New York Heart Associate (NYHA) class II, unstable angina pectoris, unexplained recurrent syncope, cardiac arrhythmia requiring treatment or family history of sudden death from cardiac-related causes
Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (New York Heart Association functional classification of >= 2; including individuals who currently use digitalis, beta-blockers, or calcium channel blockers specifically for congestive heart failure), unstable angina, myocardial infarction within 12 months of enrollment, or ventricular arrhythmia
History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, New York Heart Association Class II or greater congestive heart failure, or other clinically significant cardiac diseases within 12 months of enrollment
Myocardial infarction within 6 months before starting therapy, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication.
Patients with a history of unstable or newly diagnosed angina pectoris, recent myocardial infarction (within 6 months of enrollment) or New York Heart Association class II–IV congestive heart failure
Patients with unstable angina, new onset angina within the last 3 months, myocardial infarction within the last 6 months, and current congestive heart failure New York Heart Association class III or higher
Patients with a history of New York Heart Association class 3 or 4 heart failure, or history of myocardial infarction, unstable angina, or cerebrovascular accident (CVA) within 6 months of protocol registration
Significant active cardiac disease within the previous 6 months including: New York Heart Association (NYHA) class 4 congestive heart failure (CHF), unstable angina, myocardial infarction
History of New York Heart Association class 3-4 congestive heart failure or patients with history myocardial infarction within 6 months of starting study treatment
Myocardial infarction within 6 months before starting therapy, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication
Patients with a history of serious cardiac events defined as: New York Heart Association class 3 or 4 heart failure, or history of myocardial infarction, unstable angina or cerebrovascular accident (CVA) within 6 months of protocol registration
Current uncontrolled cardiac disease such as angina or myocardial infarction, congestive heart failure including New York Heart Association functional classification of 3, or arrhythmia requiring treatment
Myocardial infarction within 6 months before starting therapy, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication
Clinically significant heart disease (eg, congestive heart failure of New York Heart Association Class 3 or 4 angina, not well controlled by medication, or myocardial infarction within 6 months)
Patients with history of serious cardiac events defined as: New York Heart Association class 3 or 4 heart failure, history of myocardial infarction, unstable angina, or cardiovascular accident (CVA) within 6 months of protocol registration; history of PR prolongation or atrioventricular (AV) block
Patients with active heart disease (New York Heart Association [NYHA] class 3-4 as assessed by history and physical examination, unstable angina/stroke/myocardial infarction within the last 6 months)
No significant cardiac disease, including the following: unstable angina, New York Heart Association class II-IV congestive heart failure, myocardial infarction within six months prior to study enrollment
Patients with any of the following:\r\n* Uncontrolled angina at time of consent OR\r\n* > New York Heart Association (NYHA) class II congestive heart failure at time of consent OR\r\n* Myocardial infarction (MI) within 6 months prior to start of study treatment
Patients with New York Heart Association Class III or IV congestive heart failure or left ventricular ejection fraction (LVEF) < 50%, or significant uncontrolled cardiac disease, current diagnosis of unstable angina, uncontrolled congestive heart failure, new myocardial infarction, or ventricular arrhythmia requiring medication;
Have unstable angina, clinically significant cardiac arrhythmia, New York Heart Association Class 3 or 4 congestive heart failure, or prolonged QT interval corrected wave of greater than 470 ms.
Subjects with uncontrolled high blood pressure, unstable angina, symptomatic congestive heart failure (New York Heart Association [NYHA] class 3), myocardial infarction within the past 6 months or serious uncontrolled cardiac arrhythmia are not eligible
Patients with uncontrolled hypertension (> 160/95), unstable coronary disease evidenced by uncontrolled arrhythmias, unstable angina, decompensated congestive heart failure (CHF) (> New York Heart Association [NYHA] class II), or myocardial infarction within 6 months of enrollment
Clinically evident congestive heart failure > class II of the New York Heart Association (NYHA) guidelines, unstable angina or myocardial infarction within the previous 6 months
Unstable cardiovascular function: \r\n* Electrocardiography (ECG) abnormalities requiring treatment, or   \r\n* Congestive heart failure (CHF) of New York Heart Association (NYHA) class >= 3 \r\n* Myocardial infarction (MI) within 3 months
Subject has unstable angina, a significant cardiac arrhythmia, or New York Heart Association Class 3 or 4 congestive heart failure.
Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (New York Heart Association functional classification of ?2; including individuals who currently use digitalis, beta -blockers, or calcium channel blockers specifically for congestive heart failure), unstable angina, myocardial infarction within 12 months of enrollment, or ventricular arrhythmia
Myocardial infarction, symptomatic congestive heart failure (New York Heart Association Classification > Class II), unstable angina, or serious uncontrolled cardiac arrhythmia within the last 6 months of Cycle 1 Day 1
History of myocardial infarction and unstable angina within 6 months before study drug treatment; symptomatic congestive heart failure (Congestive Heart Failure New York Heart Association Class III or IV); congenital long QT syndrome; or ventricular arrhythmias defined as grade ?2 according to NCI CTCAE, v4
Myocardial infarction within 6 months of study day 1, symptomatic congestive heart failure (New York Heart Association > class II)
Significant cardiac disease, including the following: unstable angina, New York Heart Association class II-IV congestive heart failure, myocardial infarction within six months prior to study enrollment.
No history of a congestive heart failure, myocardial infarction, unstable angina, uncontrolled arrhythmia, or any class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification in the last 6 months
Myocardial infarction, symptomatic congestive heart failure (New York Heart Association Classification > Class II), unstable angina, or serious uncontrolled cardiac arrhythmia within the last 6 months of C1D1
Clinically significant heart disease (eg, congestive heart failure of New York Heart Association Class 3 or 4, angina not well controlled by medication, or myocardial infarction within 6 months)
Myocardial infarction within 6 months before starting therapy, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication
? Grade 2 cardiac arrhythmia or uncontrolled atrial fib of any grade; Class 3 or 4 New York Heart Association congestive heart failure; history of severe/unstable angina, myocardial infarction or cerebrovascular accident within 6 months
Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (New York Heart Association functional classification of >= 2, including individuals who currently use digitalis specifically for congestive heart failure), unstable angina, myocardial infarction within 12 month of enrollment or ventricular arrhythmia
Unstable angina and/or decompensated congestive heart failure in the last 6 months, transmural myocardial infarction within the last 6 months, New York Heart Association functional class II or higher congestive heart failure requiring hospitalization within 12 months prior to registration, serious or inadequately controlled cardiac arrhythmia, significant vascular and peripheral vascular disease, evidence of bleeding diathesis or coagulopathy
Patients with a history of unstable or newly diagnosed angina pectoris, recent myocardial infarction (within 6 months of enrollment) or New York Heart Association class II–IV congestive heart failure
No patients with a history of cardiac disease: congestive heart failure > class II New York Heart Association (NYHA); active coronary artery disease (CAD) (myocardial infarction or unstable angina within 6 months prior to study entry)
Symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication (atrial fibrillation is permitted)
Unstable angina, congestive heart failure (New York Heart Association (NYHA) > class II), uncontrolled hypertension (diastolic blood pressure > 100 mmHg), or recent (within 1 year) myocardial infarction
Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (New York Heart Association functional classification of >= 2), unstable angina, myocardial infarction within 12 months of enrollment, or ventricular arrhythmia
Participant has active, uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (New York Heart Association functional classification of >= 2), unstable angina, myocardial infarction within 12 months of enrollment, or ventricular arrhythmia
Unstable angina, congestive heart failure (New York Heart Association (NYHA) > Class II), uncontrolled hypertension (diastolic blood pressure > 100mmHg), or recent (within 1 year) myocardial infarction
History of myocardial infarction or other evidence of arterial thrombotic disease (angina), symptomatic congestive heart failure (New York Heart Association >= grade 2), unstable angina pectoris, or cardiac arrhythmia; Note: allowed only if patient has no evidence of active disease for at least 6 months prior to randomization
a. Class I and above myocardial ischemia or myocardial infarction, cardiac arrhythmia and Class 2 or above congestive heart failure classified according to New York Heart Association (NYHA)
Myocardial infarction within 6 months prior to C1D1 treatment, and/or prior diagnoses of congestive heart failure (New York Heart Association Class III or IV), unstable angina, unstable cardiac arrhythmia requiring medication; and/or the participant is at risk for polymorphic ventricular tachycardia (eg, hypokalemia, family history or long QT syndrome)
History of myocardial infarction, severe/unstable angina, or symptomatic congestive heart failure (New York Heart Failure [NYHA] class III or IV congestive heart failure) within 6 months prior to study enrollment or left ventricular ejection fraction (LVEF) < 50%
Documented myocardial infarction or unstable/uncontrolled cardiac disease (eg, unstable angina, congestive heart failure [New York Heart Association > Class III]) within 6 months or enrollment
Myocardial infarction within 6 months prior to C1D1, and/or prior diagnoses of congestive heart failure (New York Heart Association Class III or IV), unstable angina, unstable cardiac arrhythmia requiring medication; and/or the subject is at risk for polymorphic ventricular tachycardia (eg, hypokalemia, family history or long QT syndrome)
Unstable cardiovascular function:\r\n* Electrocardiogram (ECG) abnormalities requiring treatment, or\r\n* Congestive heart failure (CHF) of New York Heart Association (NYHA) class >= 3\r\n* Myocardial infarction (MI) within 3 months
Major cardiac abnormalities as defined but not limited to the following: uncontrolled angina or unstable life-threatening arrhythmias, history of myocardial infarction within 12 weeks prior to Baseline, Class 3 or higher New York Heart Association (NYHA) congestive heart failure, or severe cardiac insufficiency, persistent (3 consecutive electrocardiograms (ECGs) performed ? 5 minutes apart) prolongation of the QTc (Fridericia) interval to > 480 msec.
Current uncontrolled cardiac disease such as angina or myocardial infarction, congestive heart failure including New York Heart Association functional classification of 3, or arrhythmia requiring treatment.
Patients with uncontrolled hypertension (> 160/95), unstable coronary disease evidenced by uncontrolled arrhythmias, unstable angina, decompensated congestive heart failure (CHF) (> New York Heart Association [NYHA] class II), or myocardial infarction within 6 months of study will be excluded
Myocardial infarction, unstable angina within the past 6 months, or congestive heart failure New York Heart Association Class II or greater
Symptomatic congestive heart failure (New York Heart Association Classification > Class II), unstable angina, or unstable cardiac arrhythmia requiring medication
Myocardial infarction, symptomatic congestive heart failure (New York Heart Association Classification > Class II), unstable angina, or serious uncontrolled cardiac arrhythmia within the last 6 months of study Day 1
Unstable cardiovascular function:\r\n* Electrocardiogram (ECG) abnormalities requiring treatment, or\r\n* Congestive heart failure (CHF) of New York Heart Association (NYHA) class >= 3\r\n* Myocardial infarction (MI) within 3 months\r\n* Symptomatic ischemia or angina
Congestive heart failure > Class II New York Heart Association Functional Classification, current pericarditis, myocardial infarction within 6 months, or symptomatic coronary artery disease.
Myocardial infarction within 6 months of anti-MIF antibody administration, congestive heart failure (New York Heart Association Class III or Class IV), unstable angina, unstable cardiac arrhythmia requiring medication, or risk factors for polymorphic ventricular tachycardia
Participants with history of cardiovascular disease manifested as:\r\n* History of myocardial infarction\r\n* Unstable angina\r\n* Currently taking medication for treatment of angina\r\n* History of coronary artery bypass surgery\r\n* New York Heart Association class 3 or 4 heart failure
Myocardial infarction within 6 months of study day 1, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication, or uncontrolled hypertension in the opinion of the investigator
Have a history of New York Heart Association class ?3, unstable angina, myocardial infarction 6 months prior to study drug
Unstable angina, myocardial infarction, cerebrovascular accident, >= Class II congestive heart failure according to the New York Heart Association Classification for Congestive Heart Failure within 6 months before enrollment.
Myocardial infarction within 6 months of study day 1, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication, or uncontrolled hypertension
Patients with uncontrolled hypertension (> 160/95), unstable coronary disease evidenced by uncontrolled arrhythmias, unstable angina, decompensated congestive heart failure (CHF) (> New York Heart Association [NYHA] class II), or myocardial infarction within 6 months of study will be excluded
Unstable cardiovascular function:\r\n* Electrocardiography (ECG) abnormalities requiring treatment, or\r\n* Congestive heart failure (CHF) of New York Heart Association (NYHA) class >= 3\r\n* Myocardial infarction (MI) within 3 months
Unstable cardiovascular function:\r\n* Symptomatic ischemia\r\n* Congestive heart failure New York Heart Association (NYHA) class > 3\r\n* Myocardial infarction (MI) within 3 months
Patient has uncontrolled angina, congestive heart failure (New York Heart Association > class II or known ejection fraction < 40%), uncontrolled cardiac arrhythmia or hypertension, or acute myocardial infarction within 3 months
Patient has uncontrolled angina, congestive heart failure (New York Heart Association > class II or known ejection fraction < 40%), uncontrolled cardiac arrhythmia or hypertension, or acute myocardial infarction within 3 months
Myocardial infarction within 6 months before starting therapy, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication
Myocardial infarction within 6 months before starting therapy, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication
Significant active cardiac disease within 6 months prior to enrollment, including but not limited to New York Heart Association class 4 cardiac heart failure, unstable angina, myocardial infarction
New York Heart Association class I or less; ordinary physical activity does not cause undue fatigue, palpitations, dyspnea, or angina pain; patients 60 years or older must have a left ventricular ejection fraction (LVEF) at rest >= 40% measured by echocardiogram or multi-gated acquisition (MUGA)
History of significant cardiovascular disease unless the disease is well-controlled or history of myocardial infarction in the past 6 months; significant cardiac diseases includes second/third degree heart block; significant conduction abnormalities, significant ischemic heart disease; corrected QT (QTc) interval > 480 msec at baseline (using Bazett’s formula and read by local cardiologist); poorly controlled hypertension; congestive heart failure of New York Heart Association (NYHA) class II or worse (slight limitation of physical activity; comfortable at rest, but ordinary physical activity results in fatigue, palpitation, or dyspnea) and inability to tolerate intravenous hydration necessary for study therapy administration
History of significant cardiovascular disease unless the disease is well controlled. Significant cardiac disease includes second/third degree heart block; significant ischemic heart disease; poorly controlled hypertension; congestive heart failure of the New York Heart Association (NYHA) Class II or worse (slight limitation of physical activity; comfortable at rest, but ordinary activity results in fatigue, palpitation or dyspnea).
History of significant cardiovascular disease unless the disease is well controlled. Significant cardiac disease includes second/third degree heart block; significant ischemic heart disease; poorly controlled hypertension; congestive heart failure of the New York Heart Association (NYHA) Class II or worse (slight limitation of physical activity; comfortable at rest, but ordinary activity results in fatigue, palpitation or dyspnea)
Cardiovascular disability status of New York Heart Association Class greater than or equal to 3.
A cardiovascular disability status of New York Heart Association class >= 2
Participant has a cardiovascular disability status of New York Heart Association Class > 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain.
Participant has cardiovascular disability status of New York Heart Association Class >
Class 2 is defined as cardiac disease which subjects are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or angina pain. Class 3 is defined as cardiac disease which subjects are comfortable at rest but less than ordinary activity causes fatigue, palpitation, or dyspnea. Class 4 is defined as cardiac disease which subjects have an inability to carry on any physical activity without discomfort, symptoms of heart failure at rest, and if any physical activity is undertaken then discomfort increases.
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)
A cardiovascular disability status of New York Heart Association class >= 2
Patients must have no clinical signs of heart failure and meet New York Heart Association functional classification I or II defined as:\r\n* Class I – patients with no limitation of activities; they suffer no symptoms from ordinary activities\r\n* Class II – patients with slight, mild limitation of activity; they are comfortable with rest or with mild exertion
Congestive heart failure New York Heart Association (NYHA) class III or worse (marked limitation of physical activity; comfortable at rest; less than ordinary activity causes fatigue, palpitation, or dyspnea)
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)
A cardiovascular disability status of New York Heart Association Class ? 2, defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or angina pain
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)
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)
American Heart Association class I: patients with cardiac disease but without resulting limitation of physical activity; ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain; additionally, patients > 60 years of age must have a left ventricular ejection fraction of at least >= 40% demonstrated by multi gated acquisition scan (MUGA) or echocardiogram (Echo)
Congestive cardiac failure of >= Grade 3 severity according to New York Heart Association (NYHA) functional classification defined as subjects with marked limitation of activity and who are comfortable only at rest.
Patients with New York Heart Association Class II or greater congestive heart failure (Class II is defined as symptoms of fatigue, dyspnea or other symptoms with ordinary physical activity)
A cardiovascular disability status of New York Heart Association class >= 2, defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or angina pain
Class III or Class IV myocardial disease as described by the New York Heart Association; a recent history (within 6 months) of myocardial infarction, or symptomatic arrhythmia at the time of randomization. Class III: Patients with cardiac disease resulting in marked limitation of physical activity. Such patients are comfortable at rest. Less than ordinary physical activity that causes fatigue, palpitation, dyspnea, or anginal pain. Class IV: Patients with cardiac disease resulting in inability to perform any physical activity without discomfort. Symptoms of cardiac insufficiency or anginal syndrome may be present even at rest.
Participant has a cardiovascular disability status of New York Heart Association Class greater than 2.
A cardiovascular disability status of New York Heart Association Class >/=3. Class 3 is defined as cardiac disease in which participants are comfortable at rest but have marked limitation of physical activity due to fatigue, palpitations, dyspnea, or anginal pain
Cardiovascular disability status of New York Heart Association Class greater than or equal to 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea or anginal pain.
Subject has a cardiovascular disability status of New York Heart Association Class greater or equal to 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity, results in fatigue, palpitations, dyspnea or anginal pain.
Cardiac: Left ventricular ejection fraction at rest ? 40% demonstrated by Multi Gated Acquisition Scan (MUGA) or echocardiogram. Patients with known heart disease must have a functional status no worse than American Heart Association Class I defined as patients with cardiac disease but without resulting limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain.
Subject has a cardiovascular disability status of New York Heart Association Class greater or equal to 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity, results in fatigue, palpitations, dyspnea or anginal pain.
American Heart Association (AHA) class 1 without significant limitation of physical activity
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)
Patient must not have significant cardiovascular disease, such as New York Heart Association cardiac disease (class II or greater), myocardial infarction within 3 months prior to initiation of treatment, unstable arrhythmias, or unstable angina given the higher risks associated with surgical resection
New York Heart Association congestive heart failure of grade II or above, unstable angina, myocardial infarction within the past 6 months, or serious cardiac arrhythmia associated with significant cardiovascular impairment within the past 6 months
Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months of the first dose of study drug; or cardiac arrhythmia requiring medical treatment (including oral anticoagulation)
Uncontrolled or severe cardiovascular disease, including myocardial infarction or unstable angina within six months prior to study treatment, New York Heart Association (NYHA) Class II or greater congestive heart failure, serious arrhythmias requiring medication for treatment, clinically significant pericardial disease or cardiac amyloidosis.
For Parts F and H: Cardiac disease including myocardial infarction within 6 months, unstable angina, or New York Heart Association (NYHA) Grade II or greater functional impairment.
Significant cardiovascular impairment within 6 months prior to the first dose of study drug; history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke, or cardiac arrhythmia associated with significant cardiovascular impairment
Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina.
Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction, or cerebrovascular accident within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
Uncontrolled or severe cardiovascular disease, including myocardial infarct or unstable angina within 6 months before study treatment, New York Heart Association Class II or greater congestive heart failure, serious arrhythmias requiring medication for treatment, clinically significant pericardial disease or cardiac amyloidosis.
The patient has clinically significant cardiovascular disease (e.g., uncontrolled or any New York Heart Association Class 3 or 4 congestive heart failure [Appendix 1], uncontrolled angina, history of myocardial infarction, unstable angina or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication).
Significant cardiovascular disease (New York Heart Association Class [NYHA] class II or greater); myocardial infarction within 3 month prior to randomization, unstable arrhythmias, unstable angina or a patient with a known left ventricular ejection fraction (LVEF) < 40%
Significant cardiovascular disease, such as New York Heart Association cardiac disease (class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina\r\n* Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction < 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate
Patients with uncontrolled or severe cardiovascular disease, including myocardial infarct or unstable angina within 6 months prior to start of study treatment, New York Heart Association (NYHA) Class II or greater congestive heart failure, serious arrhythmias requiring medication for treatment, clinically significant pericardial disease, or cardiac amyloidosis may not be enrolled.
Clinically significant (i.e., active) cardiovascular disease, for example cerebrovascular accidents =< 6 months prior to study enrollment, myocardial infarction =< 6 months prior to study enrollment, unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF), or serious cardiac arrhythmia uncontrolled by medication or potentially interfering with protocol treatment.
Significant cardiovascular disease, such as New York Heart Association cardiac disease (class III or greater), myocardial infarction within 3 months prior to randomization, unstable arrhythmias, or unstable angina
Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) class II, unstable angina, myocardial infarction or stroke within 6 months of the first dose of study drug
Significant cardiovascular disease (i.e. New York Heart Association [NYHA] class 3 congestive heart failure; myocardial infarction within the past 6 months; unstable angina; coronary angioplasty with the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias)
Significant cardiovascular diseases (i.e., uncontrolled hypertension, unstable angina, history of infarction within the past 3 months prior to start of study treatment, congestive heart failure > New York Heart Association (NYHA) II, serious cardiac arrhythmia)
Significant cardiovascular disease (such as New York Heart Association class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 12 months prior to initiation of study treatment, or unstable arrhythmia or unstable angina within 3 months prior to initiation of study treatment
Significant cardiovascular disease (New York Heart Associate [NYHA] class II or greater); myocardial infarction within 3 month prior to randomization, unstable arrhythmias, unstable angina or a patient with a known LVEF (left ventricular ejection fraction) < 40%
Significant cardiovascular diseases within the past 6 months including uncontrolled congestive heart failure (> New York Heart Association [NYHA] class II), myocardial infarction, unstable angina, or uncontrolled arrhythmia
Significant cardiovascular disease, such as New York Heart Association cardiac disease (class II or greater), myocardial infarction within 3 months prior to enrollment, unstable arrhythmias, or unstable angina; patients with known left ventricular ejection fraction (LVEF) < 40% will be excluded; patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or LVEF < 50%, must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate
Significant cardiovascular disease, such as:\r\n* New York Heart Association congestive heart failure class II or greater\r\n* Myocardial infarction, unstable angina or unstable arrhythmias within 3 months of enrollment\r\n* History of stroke or TIA within 3 months of enrollment\r\n* Other clinically significant arterial vascular disease within 6 months of enrollment (e.g. aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis); prior history of adequately treated venous thromboembolism > 7 days prior to cycle 1 day 1 (C1D1) on stable dose of therapeutic anticoagulation is permitted\r\n* Subjects with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction < 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate
Clinically significant (i.e. active) cardiovascular disease (e.g., myocardial infarction or arterial thromboembolic events =< 6 months prior to screening or severe or unstable angina, New York Heart Association (NYHA) class III or IV disease, grade II or greater congestive heart failure, or serious cardiac arrhythmia, or a corrected QT (QTc) interval > 470 msec)
Significant cardiovascular disease such as New York Heart Association (NYHA) class III or greater, myocardial infarction within the previous 3 months, unstable arrhythmias, unstable angina; patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction < 45% must be on a stable regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist when appropriate
Cardiovascular disease or cerebrovascular disease, for example cerebrovascular accidents or myocardial infarction ? 6 months prior to study enrollment, unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure (CHF), or serious cardiac arrhythmia uncontrolled by medication or with the potential to interfere with protocol treatment;
Significant cardiovascular disease (i.e. New York Heart Association [NYHA] class 3 congestive heart failure; myocardial infarction with the past 6 months; unstable angina; coronary angioplasty with the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias)
Significant cardiovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within the past 12 months prior to start of study treatment, congestive heart failure > New York heart association ([NYHA] II, serious cardiac arrhythmia, pericardial effusion)
Participant has a clinically significant cardiovascular disease including:\r\n* Uncontrolled hypertension, defined as systolic > 150 mmHg or diastolic > 90 mmHg\r\n* Myocardial infarction or unstable angina within 6 months prior to enrollment\r\n* New York Heart Association (NYHA) grade II or greater congestive heart failure \r\n* Participant has a grade II or greater peripheral vascular disease\r\n* Participant has a clinically significant peripheral artery disease (e.g. those with claudication, within 6 months)
Patients with clinically significant cardiovascular disease; this includes:\r\n* Myocardial infarction or unstable angina < 6 months prior to registration\r\n* New York Heart Association (NYHA) grade II or greater congestive heart failure\r\n* Serious cardiac arrhythmia requiring medication; this does not include asymptomatic, atrial fibrillation with controlled ventricular rate
Significant history of uncontrolled cardiac disease including uncontrolled hypertension, unstable angina, cerebrovascular accidents or myocardial infarction within the last 6 months, and New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF), or serious cardiac arrhythmia uncontrolled by medication
Clinically significant heart disease (i.e., active), stroke or myocardial infarction within 6 months prior to enrollment, unstable angina pectoris, congestive heart failure of grade > II according to the New York Heart Association (NYHA), or cardiac arrhythmia requiring specific treatment during the study and that may interfere with the follow-up of the study treatment or poorly controlled by treatment
Has cardiovascular impairment, history of congestive heart failure greater than NYHA Class II, uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months prior to the planned first dose of tazemetostat; or ventricular cardiac arrhythmia requiring medical treatment
Subject has a clinically significant cardiovascular disease including:\r\n* Uncontrolled hypertension\r\n* Myocardial infarction or unstable angina within 6 months prior to enrollment\r\n* New York Heart Association (NYHA) grade II or greater congestive heart failure
Significant cardiovascular disease (New York Heart Association class II or greater); myocardial infarction within 3 months prior to enrollment, unstable arrhythmias, unstable angina or a patient with a known left ventricular ejection fraction (LVEF) < 40%
Significant cardiovascular disease (i.e. New York Heart Association [NYHA] class 3 congestive heart failure; myocardial infarction with the past 6 months; unstable angina; coronary angioplasty with the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias)
Clinically significant (i.e., active) cardiovascular disease (e.g., cerebrovascular accident or myocardial infarction within 6 months prior to randomization), unstable angina, congestive heart failure (New York Heart Association class >= II) or serious cardiac arrhythmia that is uncontrolled by medication or may interfere with administration of study treatment
Patients with clinically significant cardiovascular disease; this includes: uncontrolled hypertension (greater than 140/90); myocardial infarction or unstable angina within 6 months prior to registration; New York Heart Association (NYHA) grade II or greater congestive heart failure; serious cardiac arrhythmia requiring medication; grade II or greater peripheral vascular disease; patients with clinically significant peripheral artery disease, e.g., those with claudication, within 6 months of first date of treatment on this study
Patient has clinically significant cardiovascular disease (e.g., significant cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction, cardiac arrhythmia or unstable angina, New York Heart Association Grade 3 or greater congestive heart failure, serious cardiac arrhythmia requiring medication, Grade 2 or greater peripheral vascular disease, and history of cerebrovascular accident (CVA)) within 6 months of enrollment.
Clinically significant (i.e. active) cardiovascular disease for example cerebro vascular accidents (< 6 months prior to enrolment), myocardial infarction (< 6 months prior to enrolment), unstable angina, New York Heart Association (NYHA) grade II or higher, congestive heart failure, serious cardiac arrhythmia requiring medication.
Has significant cardiovascular impairment within 12 months of the first dose of study drug: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or cerebrovascular accident (CVA) stroke, or cardiac arrhythmia associated with hemodynamic instability, significant cardiovascular impairment, or a left ventricular ejection fraction (LVEF) below the institutional normal range as determined by multigated acquisition scan (MUGA) or echocardiogram
Patients who have significant cardiovascular diseases are not eligible; these are:\r\n* Uncontrolled hypertension\r\n* Unstable angina\r\n* History of infarction within the past 12 months prior to start of study treatment\r\n* Congestive heart failure > New York Heart Association (NYHA) II\r\n* Serious uncontrolled cardiac arrhythmia\r\n* Pericardial effusion
Clinically significant (i.e., active) cardiovascular disease (e.g., cerebrovascular accident or myocardial infarction [MI] within 6 months prior to randomization), unstable angina, congestive heart failure (CHF) (New York Heart Association [NYHA] class >= NII), or serious cardiac arrhythmia that is uncontrolled by medication or may interfere with administration of study treatment
Significant cardiovascular impairment (e.g., New York Heart Association congestive heart failure of grade II or above, unstable angina, myocardial infarction within the past 6 months, or serious cardiac arrhythmia)
Clinically significant cardiovascular disease (e.g., uncontrolled or any New York Heart Association [NYHA] class 3 or 4, congestive heart failure, uncontrolled or unstable angina, history of myocardial infarction or stroke within 6 months prior to study entry, or clinically significant arrhythmias not controlled by medication)
Significant cardiovascular impairment: congestive heart failure > class II according to the New York Heart Association (NYHA), unstable angina or myocardial infarction within 6 months of enrollment, or serious cardiac arrhythmia (> grade 2)
Uncontrolled hypertension (systolic > 180 mm Hg and/or diastolic > 100 mm Hg) or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident/stroke or myocardial infarction within 6 months prior to first study medication, unstable angina, congestive heart failure (CHF) of New York Heart Association (NYHA) grade II or higher, or serious cardiac arrhythmia requiring medication
Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction, or cerebrovascular accident within 3 months prior to randomization, unstable arrhythmias, or unstable angina
Significant cardiovascular impairment: History of (a) congestive heart failure greater than New York Heart Association (NYHA) Class II, (b) unstable angina, (c) myocardial infarction, (d) stroke, or (e) cardiac arrhythmia associated with impairment within 6 months of the first dose of study drug.
Has cardiovascular impairment, history of congestive heart failure greater than NYHA Class II uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months prior to the planned first dose of tazemetostat; or ventricular cardiac arrhythmia requiring medical treatment
Significant cardiovascular disease, such as cardiac disease (New York Heart Association Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina
Has cardiovascular impairment, history of congestive heart failure greater than NYHA Class II, uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months prior to the planned first dose of tazemetostat; or ventricular cardiac arrhythmia requiring medical treatment
Uncontrolled hypertension, unstable angina, New York Heart Association grade II or greater congestive heart failure, unstable symptomatic arrhythmia requiring medication, or clinically significant peripheral vascular disease (grade II or greater)
Significant cardiovascular disease, such as New York Heart Association cardiac disease (class II or greater), myocardial infarction, or cerebrovascular accident within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months of the first dose of study drug; or cardiac arrhythmia requiring medical treatment (including oral anticoagulation).
Significant cardiovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within the past 12 months prior to start of study treatment, congestive heart failure > New York Heart Association [NYHA] II, serious cardiac arrhythmia, pericardial effusion)
Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke within 6 months of the first dose of study drug, or cardiac arrhythmia requiring medical treatment at Screening
Uncontrolled or severe cardiovascular disease, including myocardial infarct or unstable angina within 6 months prior to study treatment, New York Heart Association (NYHA) Class II or greater congestive heart failure, serious arrhythmias requiring medication for treatment, clinically significant pericardial disease, or cardiac amyloidosis.
History of significant cardiovascular disease, defined as: congestive heart failure greater than New York Heart Association (NYHA) class II according to the NYHA functional classification; unstable angina or myocardial infarction within 6 months of enrollment; or serious cardiac arrhythmia
Significant cardiovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within the past 6 months prior to start of study treatment, congestive heart failure > New York Heart Association [NYHA] II, serious cardiac arrhythmia, pericardial effusion)
No significant cardiovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within the past 12 months prior to start of study treatment, congestive heart failure > [New York Heart Association NYHA] II, serious cardiac arrhythmia, pericardial effusion)
Participant has significant active cardiac disease within the previous 6 months including unstable angina or angina requiring surgical or medical intervention, significant cardiac arrhythmia, or New York Heart Association (NYHA) class 3 or 4 congestive heart failure.
Subject has significant active cardiac disease within the previous 6 months including unstable angina or angina requiring surgical or medical intervention, significant cardiac arrhythmia, or New York Heart Association (NYHA) class 3 or 4 congestive heart failure.
Patients with clinically significant cardiovascular disease: \r\n* History of cerebrovascular accident (CVA) within 6 months \r\n* Myocardial infarction or unstable angina within 6 months \r\n* Unstable angina pectoris\r\n* New York Heart Association class III or greater congestive heart failure
Uncontrolled or severe cardiovascular disease, including myocardial infarct or unstable angina within 6 months prior to study treatment, New York Heart Association (NYHA) Class II or greater congestive heart failure, serious arrhythmias requiring medication for treatment, clinically significant pericardial disease, or cardiac amyloidosis
Significant cardiovascular impairment within 6 months as defined as (1) congestive heart failure greater than New York Heart Association Class II, (2) unstable angina, (3) myocardial infarction; (4) stroke, (5) symptomatic cardiac arrhythmia
Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction, or stroke within 6 months of the first dose of study drug, or cardiac arrhythmia requiring medical treatment at Screening.
Clinically significant cardiovascular impairment (history of congestive heart failure greater or equal to New York Heart Association [NYHA] class II, unstable/active angina or myocardial infarction [MI] =< 6 months before day 1 of this study, or serious cardiac arrhythmia)
Clinically significant cardiovascular disease, defined as myocardial infarction (or unstable angina) within 6 months of registration, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac dysrhythmia refractory to medical management; however, treated and controlled or stable/not clinically significant cardiovascular disease is allowed per evaluation by cardiologist
Patients with clinically significant cardiovascular disease: history of cerebrovascular accident (CVA) within 6 months; myocardial infarction or unstable angina within 6 months; unstable angina pectoris; New York Heart Association class > II
Subject has a clinically significant cardiovascular disease including: uncontrolled hypertension; myocardial infarction or unstable angina within 6 months prior to registration; New York Heart Association (NYHA) Grade II or greater congestive heart failure
Significant cardiovascular impairment within 12 months of the first dose of study drug: history of congestive heart failure greater than New York Heart Association Class II, unstable angina, myocardial infarction, cerebrovascular accident, or cardiac arrhythmia associated with hemodynamic instability. The following is also excluded: left ventricular ejection fraction below the institutional normal range as determined by multiple-gated acquisition scan or echocardiogram
Significant cardiac disease as defined as: unstable angina, New York Heart Association (NYHA) grade II or greater, congestive heart failure, history of myocardial infarction within 6 months
Uncontrolled or severe concurrent medical condition including cardiovascular disease (e.g., myocardial infarct, unstable angina, New York Heart Association (NYHA) Class II or greater congestive heart failure, serious arrhythmias requiring medication for treatment, clinically significant pericardial disease, cardiac amyloidosis, transient ischemic attacks, CVA, coronary artery or other vascular stents).
Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina. Patient with known coronary artery disease, congestive heart failure not meeting the above criteria, or known left ventricular ejection fraction less than 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician
Significant cardiovascular disease (i.e. New York Heart Association [NYHA] class 3 congestive heart failure; myocardial infarction with the past 6 months; unstable angina; coronary angioplasty with the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias)
11. Uncontrolled or severe cardiovascular disease, including myocardial infarct or unstable angina within 6 months prior to study treatment, New York Heart Association Class II or greater congestive heart failure, serious arrhythmias requiring medication for treatment, clinically significant pericardial disease, or cardiac amyloidosis.
Clinically significant (that is [i.e.] active) cardiovascular disease (For example [e.g.] cerebrovascular accident or myocardial infarction within 6 months prior to randomization), unstable angina, congestive heart failure (New York Heart Association Class >/= II) or serious cardiac arrhythmia that is uncontrolled by medication or may interfere with the administration of the study treatment
Clinically significant cardiovascular disease (eg, uncontrolled hypertension, myocardial infarction, unstable angina), New York Heart Association (NYHA) Grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication within 1 year prior to Day -1 (Visit 1); Grade II or greater peripheral vascular disease at study entry
History or symptoms of cardiovascular disease (New York Heart Association [NYHA] class 2, 3, or 4) within the last 6 months, particularly coronary artery disease, arrhythmias, or conduction defects with risk of cardiovascular instability, uncontrolled hypertension, clinically significant pericardial effusion, or congestive heart failure
The patient has clinically significant cardiovascular disease (e.g., uncontrolled or any New York Heart Association [NYHA] Class 3 or 4 congestive heart failure, uncontrolled angina, history of myocardial infarction, unstable angina or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication).
Patients with clinically significant cardiovascular disease (eg, significant cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction, cardiac arrhythmia or unstable angina < 6 months to enrollment, New York Heart Association (NYHA) Grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, Grade II or greater peripheral vascular disease, and history of cerebrovascular accident (CVA) within 6 months).
Significant cardiovascular impairment: congestive heart failure > class II according to the New York Heart Association (NYHA), unstable angina or myocardial infarction within 6 months of enrollment, or serious cardiac arrhythmia (> grade 2)
Cardiovascular events, such as myocardial infarction, unstable/severe angina, coronary/peripheral artery bypass graft, unstable cardiac arrhythmia requiring medication, congestive heart failure (NYHA > class II), within 2 years
History of significant cardiovascular disease (i.e. NYHA class 3 congestive heart failure; myocardial infarction with the past 6 months; unstable angina; coronary angioplasty with the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias)
Clinically significant cardiovascular disease (e.g., hypertension [blood pressure [BP] > 150/100], myocardial infarction or stroke within 6 months, unstable angina), New York Heart Association (NYHA) grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication
Patients with clinically significant cardiovascular disease: history of cerebrovascular accident (CVA) within 6 months, myocardial infarction or unstable angina within 6 months, unstable angina pectoris, New York Heart Association class CHF score II
Uncontrolled or severe cardiovascular disease, including myocardial infarct or unstable angina within 6 months prior to study treatment, New York Heart Association (NYHA) class II or greater congestive heart failure, serious arrhythmias requiring medication for treatment, clinically significant pericardial disease or cardiac amyloidosis
Significant cardiovascular impairment: history of (a) congestive heart failure greater than New York Heart Association (NYHA) Class II; (b) unstable angina; (c) myocardial infarction; (d) stroke; or (e) cardiac arrhythmia associated with hemodynamic instability within 6 months of the first dose of study drugs
Significant cardiovascular disease such as New York Heart Association (NYHA) class II or greater, myocardial infarction within the previous 3 months of first study treatment, unstable arrhythmias, unstable angina; patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction < 50% must be on a stable regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist when appropriate
Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac disease (Class II or greater), myocardial infarction within 3 months prior to Day 1, unstable arrhythmias, or unstable angina
Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac disease (class II or greater), myocardial infarction within 3 months prior to randomization, unstable arrhythmias, or unstable angina; patients with a known left ventricular ejection fraction (LVEF) < 40% will be excluded; patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or LVEF < 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate
New York Heart Association congestive heart failure of grade II or above, unstable angina, myocardial infarction within the past 6 months, or serious cardiac arrhythmia associated with significant cardiovascular impairment within the past 6 months; ejection fraction (EF) by multi-gated acquisition (MUGA) or echo should not be less than the institutional lower limit of normal
Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or cerebral vascular accident within 6 months of the first dose of study drug, or cardiac arrhythmia associated with hemodynamic instability.
Any of the following cardiac conditions:\r\n* Documented New York Heart Association (NYHA) class III or IV congestive heart failure\r\n* Myocardial infarction within 6 months prior to randomization\r\n* Unstable angina within 6 months prior to randomization\r\n* Symptomatic arrhythmia
Patient has, in the opinion of the treating investigator, any intercurrent conditions that could pose an undue medical hazard or interfere with the interpretation of the study results; these conditions include, but not limited to: congestive heart failure (New York Heart Association (NYHA) Class III or IV), unstable angina, cardiac arrhythmia requiring treatment, recent (within the prior 6 months) myocardial infarction, acute coronary syndrome or stroke, severe obstructive pulmonary disease, hypertension requiring more than 2 medications for adequate control, or diabetes mellitus with more than 2 episodes of ketoacidosis in the prior 12 months
Have 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.
Patients must not have clinically significant cardiovascular disease (New York Heart Association class III or IV heart failure), uncontrolled clinically significant atrial or ventricular cardiac arrhythmias, or any of the following within the past 6 months: myocardial infarction, new evidence of transmural infarction on electrocardiogram (ECG), unstable angina, coronary angioplasty
New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG
Received treatment for unstable angina within the prior year, myocardial infarction within the prior year, cerebro-vascular attack within the prior year, history of New York Heart Association grade III or greater congestive heart failure, or current serious cardiac arrhythmia requiring medication except atrial fibrillation.
Active angina or Class III or IV Congestive Heart Failure (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 12 months of the first dose of study drug, including myocardial infarction, unstable angina, Grade 2 or greater peripheral vascular disease, congestive heart failure, uncontrolled hypertension, or arrhythmias not controlled by medication
Active coronary artery disease requiring treatment, myocardial infarction within the prior year, New York Heart Association grade III or greater congestive heart failure, cerebro-vascular attack within the prior year, or current serious cardiac arrhythmia requiring medication except atrial fibrillation.
Congestive heart failure (CHF) New York (NY) Heart Association class III or IV; unstable coronary artery disease (myocardial infarction [MI] more than 6 months prior to study entry is permitted); or serious cardiac arrhythmia
Congestive heart failure (New York Heart Association Class III or IV), myocardial infarction within 12 months before starting study treatment, or unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris.
Congestive heart failure (New York Heart Association Class III or IV) or unstable angina pectoris. Previous history of myocardial infarction within 1 year prior to study entry, uncontrolled hypertension or uncontrolled arrhythmias
Evidence of New York Heart Association (NYHA) class III or IV cardiac disease, or presence of unstable life-threatening arrhythmia, or history of myocardial infarction during the past 6 months
New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, or unstable arrhythmia.
History of unstable or deteriorating cardiac disease within the previous 6 months prior to screening including but not limited to the following:\r\n* Unstable angina or myocardial infarction\r\n* Congestive heart failure (New York Heart Association [NYHA] class III or IV)\r\n* Uncontrolled clinically significant arrhythmias.
New York Heart Association (NYHA) Class III or IV cardiac disease, myocardial infarction, within the past 6 months, unstable arrhythmia, or known pericardial disease.
10. Those with New York Heart Association functional classification II, III or IV; active cardiac conditions including unstable coronary syndromes (unstable or severe angina, recent myocardial infarction), worsening or new-onset congestive heart failure, significant arrhythmias and severe valvular disease must be evaluated for risks of undergoing general anesthesia.
Active cardiac disease defined as symptomatic congestive heart failure, history of New York Heart Association (NYHA) class III or IV heart failure, uncontrollable supraventricular arrhythmias, any history of a ventricular arrhythmia, active angina pectoris, myocardial infarction or coronary intervention within 6 months of registration
No history of any of the following =< 6 months of registration:\r\n* Myocardial infarction or unstable angina\r\n* New York Heart Association grade III or greater congestive heart failure \r\n* Cerebrovascular accident \r\n* Grade 3 or 4 peripheral ischemia\r\n* Grade 3 or 4 thromboembolic event
Active coronary artery disease requiring treatment, myocardial infarction within the prior year, New York Heart Association grade III or greater congestive heart failure, cerebro-vascular attack within the prior year, or current serious cardiac arrhythmia requiring medication except atrial fibrillation.
Have clinically significant cardiac disease (New York Heart Association class III or IV) including pre-existing arrhythmia, uncontrolled angina pectoris, myocardial infarction one year prior to study entry, or grade 2 or higher compromised left ventricular ejection fraction
The patient has active heart disease including myocardial infarction within previous 3 months, symptomatic coronary artery disease, arrhythmias not controlled by medication, unstable angina pectoris, or uncontrolled congestive heart failure (NYHA class III and IV).
Congestive heart failure (New York Heart Association Class III or IV), myocardial infarction within 12 months before starting study treatment, or unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris.
New York Heart Association classification III or IV cardiovascular disease or recent myocardial infarction or unstable angina pectoris or cardiac arrhythmia (< 30 days)
Patients with a serious cardiac condition, such as congestive heart failure; New York Heart Association class III/IV heart disease; unstable angina pectoris; myocardial infarction within the last 3 months; valvulopathy that is severe, moderate, or deemed clinically significant despite medical intervention; or arrhythmias that are symptomatic or refractory to medical intervention
Evidence of current uncontrolled cardiovascular conditions (New York Heart Association [NYHA] class III or IV), including hypertension, cardiac arrhythmias, congestive heart failure, unstable angina, or myocardial infarction within the past 6 months; Note: prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
Cardiovascular disease that meets one of the following: congestive heart failure (New York Heart Association class III or IV), active angina pectoris, or recent myocardial infarction (within the last 6 months)
Significant cardiovascular disease with New York Heart Association (NYHA) class II, III or IV symptoms, or hypertrophic cardiomegaly, or restrictive cardiomegaly, or myocardial infarction within 3 months prior to enrollment, or unstable angina, or unstable arrhythmia
No clinically significant cardiac event such as myocardial infarction; New York Heart Association (NYHA) classification of heart disease >= 2 within 3 months prior to registration for protocol therapy
Significant cardiovascular disease or condition including:\r\n* Congestive heart failure (CHF) currently requiring therapy.\r\n* Class III or IV cardiovascular disease according to the New York Heart Association (NYHA) functional criteria.\r\n* Need for antiarrhythmic medical therapy for a ventricular arrhythmia.\r\n* Severe conduction disturbance (e.g. 3rd degree heart block).\r\n* Unstable angina pectoris (i.e. last episode =< 6 months prior to first dose of protocol-indicated treatment).\r\n* Uncontrolled (per investigator judgment) hypertension.\r\n* Myocardial infarction within 6 months prior to starting trial treatment.\r\n* Fridericia's correction formula (QTcF) > 450 ms in men, or > 470 ms in women.
Congestive heart failure (New York Heart Association class III or IV), myocardial infarction within 12 months before starting study treatment, or unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris
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* Cardiac arrhythmias not controlled with medication;\r\n* Corrected QT (QTcF) > 470 ms at baseline
Clinically significant cardiac illness including New York Heart Association (NYHA) class III or class IV heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, or >= grade 3 cardiac arrhythmias noted =< 14 days prior to registration
Cardiac risk factors including:\r\n* Patients experiencing cardiac event(s) (acute coronary syndrome, myocardial infarction, or ischemia) within 3 months of signing consent\r\n* Patients with a New York Heart Association classification of III or IV
Research participants with a known history of congestive heart failure (CHF) or cardiac symptoms consistent with New York Heart Association (NYHA) classification III-IV within 6 months prior to Day 1 of protocol treatment, cardiomyopathy, myocarditis, myocardial infarction (MI), exposure to cardiotoxic medications or with clinical history suggestive of the above must have an electrocardiogram (EKG) and echocardiogram (ECHO) performed within 42 days prior to registration and as clinically indicated while on treatment
Congestive heart failure (New York Heart Association Class III or IV) or unstable angina pectoris. Previous history of myocardial infarction within 1 year prior to study entry, uncontrolled hypertension or uncontrolled arrhythmias
Significant active cardiac disease within 6 months prior to the start of study treatment, including New York Heart Association (NYHA) Class III or IV congestive heart failure; myocardial infarction, unstable angina and/or stroke; or LVEF <40% by echocardiogram (ECHO), or by other methods according to institutional practice, obtained within 28 days prior to the start of study treatment
Had any of the following within 6 months before randomization: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, congestive heart failure (New York Heart Association Class III or IV)
Symptomatic congestive heart failure (New York Heart Association classification III or IV cardiovascular disease, myocardial infarction =< 6 months prior to registration, unstable angina pectoris or cardiac arrhythmia =< 3 months prior to registration, or cardiac arrhythmia
Has known cardiopulmonary disease defined as unstable angina, clinically significant arrhythmia, congestive heart failure (New York Heart Association Class III or IV), and/or myocardial infarction within 6 months before first dose, or severe pulmonary hypertension.
History of pericarditis or pericardial effusion that had required medical or surgical intervention in the last 6 months, or myocardial infarction or arterial thromboembolic events within 6 months, or experiencing severe or unstable angina, or New York Heart Association (NYHA) class III or IV disease, or a corrected QC (QTc) interval > 0.47 seconds
Impaired cardiac function or clinically significant cardiac disease including the following:\r\n* New York Heart Association grade III or IV congestive heart failure\r\n* Myocardial infarction within the last 12 months.\r\n* Subjects with impaired left ventricular ejection fraction (LVEF) (< 50%)
Significant cardiovascular disease such as New York Heart Associate Class III/IV, cardiac failure, myocardial infarction within 6 months prior to enrolment, unstable arrhythmia, or evidence of ischemia on ECG.
Presence of cardiac impairment defined as:\r\n* Prior history of cardiovascular disease including heart failure that meets New York Heart Association (NYHA) class III and IV definitions; OR \r\n* History of myocardial infarction/active ischemic heart disease within one year of study entry; OR \r\n* Uncontrolled dysrhythmias; OR \r\n* Poorly controlled angina
New York Heart Association classification III or IV cardiovascular disease or recent myocardial infarction or unstable angina pectoris or cardiac arrhythmia =< 30 days prior to registration
Patients with any of the following cardiac conditions:\r\n* Symptomatic restrictive cardiomyopathy\r\n* Unstable angina within 4 months prior to enrollment\r\n* New York Heart Association functional class III-IV heart failure on active treatment\r\n* Symptomatic pericardial effusion
Has the any of the following cardiac history:\r\n* Active heart disease including myocardial infarction within previous 3 months\r\n* Symptomatic coronary artery disease\r\n* Arrhythmias not controlled by medication\r\n* Unstable angina pectoris\r\n* Uncontrolled or symptomatic congestive heart failure (New York Heart Association [NYHA] class III and IV)
Has active angina or Class III or IV Congestive Heart Failure (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 6 months of randomization, including myocardial infarction, unstable angina, Grade 2 or greater peripheral vascular disease, congestive heart failure, or arrhythmias not controlled by medication.
Clinically significant cardiac illness including New York Heart Association (NYHA) class III or class IV heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, or >= grade 3 cardiac arrhythmias noted =< 14 days prior to registration
Clinically significant heart disease, including the following:\r\n* Active severe angina pectoris prior to registration\r\n* Acute myocardial infarction prior to registration\r\n* New York Heart Association classification IV cardiovascular disease or symptomatic class III disease\r\n* Note: patients with any of the above may be allowed after discussion amongst the investigators including the principal investigator
Unstable cardiac disease as defined by one of the following:\r\n* Cardiac events such as myocardial infarction (MI) within the past 6 months\r\n* NYHA (New York Heart Association) heart failure class III-IV\r\n* Uncontrolled atrial fibrillation or hypertension
New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG
Impaired cardiac function or clinically significant cardiac disease including the following:\r\n* New York Heart Association class III or IV congestive heart failure\r\n* Myocardial infarction within the last 12 months\r\n* Subjects known to have impaired left ventricular ejection fraction (LVEF) according to institutional standards
New York Heart Association class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on electrocardiogram (ECG)
History of myocardial infarction within 6 months before study entry, unstable congestive heart failure (New York Heart Association, NYHA Stage III-IV), angina pectoris, or transient ischemic attack or cardiac arrhythmia requiring medical therapy
Subjects with a history of a cardiovascular illness including: congestive heart failure (New York Heart Association grade III or IV); unstable angina or myocardial infarction within the previous 6 months; or symptomatic cardiac arrhythmia despite medical management
Patients who have significant cardiac disease, including but not limited to history of congestive heart failure (New York Heart Association Class III/IV; see Appendix 7), unstable angina, or uncontrolled cardiac arrhythmia.
Have New York Heart Association (NYHA) Class III or IV heart failure, unstable angina, or a history of recent (within 6 months) myocardial infarction or sustained (> 30 seconds) ventricular tachyarrhythmias
History of myocardial infarction (MI) or New York Heart Association (NYHA) Class II-IV congestive heart failure within 6 months of the administration of the first dose of ARQ 751 (MI occurring > 6 months of the first dose of ARQ 751 will be permitted); Grade 2 or worse conduction defect (e.g., right or left bundle branch block)
Have 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.
Significant active cardiac disease within the previous 6 months, including: New York Heart Association (NYHA) class III or IV congestive heart failure; unstable angina or angina requiring surgical or medical intervention, and/or; myocardial infarction
Clinically significant heart disease, including the following:\r\n* Active severe angina pectoris within 3 months prior to registration\r\n* Acute myocardial infarction within 3 months prior to registration\r\n* New York Heart Association classification IV cardiovascular disease or symptomatic class III disease\r\n** Note: patients with any of the above may be allowed after discussion amongst the investigators including the principal investigator
Serious cardiac condition within the last 6 months, such as uncontrolled arrhythmia, myocardial infarction, unstable angina or heart disease defined by the New York Heart Association (NYHA) Class III or Class IV
Significant cardiac disease as determined by the investigator including:\r\n* Known or suspected cardiac amyloidosis\r\n* Congestive heart failure of class III or IV of the New York Heart Association (NYHA) classification\r\n* Uncontrolled angina, hypertension or arrhythmia\r\n* Myocardial infarction in the past 6 months\r\n* Any uncontrolled or severe cardiovascular disease
NYHA Class III-IV heart failure, myocardial infarction <6 months prior to study entry, and/or serious arrhythmia requiring anti-arrhythmic therapy
Subjects must not have New York Heart Association (NYHA) class III or IV heart failure, unstable angina, or a history of recent (within 6 months) myocardial infarction or sustained (> 30 seconds) ventricular tachyarrhythmias
Have clinically significant cardiac disease (New York Heart Association, class III or IV) including pre-existing arrhythmia, uncontrolled angina pectoris, myocardial infarction 1 year prior to study entry, or a known history of grade 2 or higher compromised left ventricular ejection fraction
Patients must not have any grade III/IV cardiac disease as defined by the New York Heart Association (NYHA) criteria unstable angina pectoris, or myocardial infarction within 6 months of registration; patients with a history of myocardial infarction or irregular heart rate within 6 months prior to registration should be evaluated by a cardiologist prior to registration
Patients must not have any of the following: New York Heart Association (NYHA) class 3 or 4 congestive heart failure; myocardial infarction within the past 12 months, acute coronary syndrome, diabetes mellitus with ketoacidosis or chronic obstructive pulmonary disease (COPD) requiring hospitalization in the preceding 6 months; or any other intercurrent medical condition that contra-indicates treatment with sEphB4HSA or places the patient at undue risk for treatment related complications
Serious medical illness, such as significant cardiac disease (e.g. symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmia, pericardial disease or New York Heart Association class III or IV), or severe debilitating pulmonary disease, that would potentially increase patients’ risk for toxicity
History of myocardial infarction (MI) or congestive heart failure defined as Class II to IV per the New York Heart Association (NYHA) classification within 6 months of the first dose of ARQ 092 (MI that occurred > 6 months prior to the first dose of ARQ 092 will be permitted)
Patients with any of the following:\r\n* History of myocardial infarction within six months\r\n* Unstable angina\r\n* Resting electrocardiogram (ECG) with clinically significant abnormal findings\r\n* New York Heart Association (NYHA) classification of III or IV
Active heart disease including myocardial infarction within previous 3 months, symptomatic coronary artery disease, arrhythmias not controlled by medication, or uncontrolled congestive heart failure (New York Heart Association class III and IV)
Clinically significant cardiac disease, including major cardiac dysfunction, such as uncontrolled angina, clinical congestive heart failure with New York Heart Association (NYHA) class III or IV, ventricular arrhythmias requiring anti-arrhythmic therapy, recent (within 6 months) myocardial infarction or unstable coronary artery disease
Patients with active unstable angina, concomitant clinically significant active arrhythmias, myocardial infarction within 6 months, or congestive heart failure New York Heart Association class III-IV; patients with a cardiac ejection fraction (as measured by either multi gated acquisition scan [MUGA] or echocardiogram) < 40% are excluded
Cardiac dysfunction defined as myocardial infarction within 6 months of study entry, New York Heart Association Class III or IV heart failure, uncontrolled dysrhythmias or poorly controlled angina.
Patients with any of the following cardiac conditions:\r\n* Symptomatic restrictive cardiomyopathy\r\n* Unstable angina within 4 months prior to enrollment\r\n* New York Heart Association functional class III-IV heart failure on active treatment\r\n* Symptomatic pericardial effusion
Patients with pre-existing cardiovascular disease requiring ongoing treatment; this includes: a) congestive heart failure class III/IV congestive heart failure (CHF) per New York Heart Association (NYHA) criteria; b) cardiomyopathy; c) uncontrolled cardiac arrhythmia; d) unstable angina pectoris; e) recent myocardial infarction (MI) (within 6 months)
Patients with clinically significant cardiovascular co-morbidities including: congestive heart failure (New York Heart Association class III-IV heart disease), unstable angina pectoris, cardiac arrhythmias requiring medication or a pacemaker; myocardial infarction within the past six months; stroke within the past 6 months; or hypertension requiring more than 2 medications for blood pressure control.
Serious medical illness, such as significant cardiac disease (e.g. symptomatic congestive heart failure, unstable angina pectoris, coronary artery disease, myocardial infarction within the past 3 months, uncontrolled cardiac arrhythmia, pericardial disease or New York Heart Association class III or IV), or severe debilitating pulmonary disease, that would potentially increase patients’ risk for toxicity
Clinically significant cardiac disease, including major cardiac dysfunction, such as uncontrolled angina, clinical congestive heart failure with New York Heart Association (NYHA) class III or higher, ventricular arrhythmias requiring antiarrhythmic therapy, recent (within 6 months) myocardial infarction or unstable coronary artery disease
New York Heart Association (NYHA) Class III or IV, cardiac disease, myocardial infarction within 4months prior to Day 1, unstable arrhythmia or symptomatic peripheral arterial vascular disease
Patients with pre-existing cardiovascular disease requiring ongoing treatment; this includes: congestive heart failure III/IV as defined by New York Heart Association (NYHA); uncontrolled cardiac arrhythmia; unstable angina pectoris; and recent myocardial infarction (MI) (within 6 months)
Those with New York Heart Association functional classification II, III or IV active cardiac conditions, including unstable coronary syndromes (unstable or severe angina, recent myocardial infarction), worsening or new-onset congestive heart failure, significant arrhythmias and severe valvular disease must be evaluated for risks of undergoing general anesthesia.
Criteria 8 Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, uncontrolled arrhythmias, clinically significant electrocardiogram (ECG) abnormalities, screening ECG with corrected QT interval (QTc) of > 470 msec, pericardial disease, or myocardial infarction within 4 months prior to randomization
Patient has a history of cardiac dysfunction 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 LVEF function\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-International Society of Hypertension [WHO-ISH] guidelines)\r\n* Documented cardiomyopathy
Patient with grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e. congestive heart failure, myocardial infarction within 6 months before baseline) Patient with any condition that the physician judges could be detrimental to subjects participating in this study; including any clinically important deviations from normal clinical laboratory values or concurrent medical events Previous treatment
Significant cardiac disease including heart failure that meets New York Heart Association (NYHA) class III and IV definitions; history of myocardial infarction within one year of study entry; uncontrolled dysrhythmias; or poorly controlled angina.
Cardiac disease, specifically restrictive cardiomyopathy, unstable angina within the last 6 months prior to enrollment, New York Heart Association functional class III-IV heart failure on active treatment with normalized LVEF on therapy, and symptomatic pericardial effusion
Symptomatic arterial peripheral vascular disease or significant cardiovascular disease or condition including:\r\n* Congestive heart failure (CHF) currently requiring therapy\r\n* Class III or IV cardiovascular disease according to the New York Heart Association (NYHA) functional criteria\r\n* Need for antiarrhythmic medical therapy for a ventricular arrhythmia\r\n* Severe conduction disturbance (e.g. third [3rd] degree heart block)\r\n* Unstable angina pectoris (i.e. last episode =< 6 months prior to first dose of protocol-indicated treatment)\r\n* Uncontrolled (per investigator judgment) hypertension\r\n* Myocardial infarction within 6 months prior to starting trial treatment\r\n* Corrected QT interval by Fridericia (QTcF) > 450 ms in men, or > 470 ms in women
Subject has any one of the following:\r\n* Clinically significant abnormal electrocardiogram (ECG) finding at screening\r\n* Congestive heart failure (New York Heart Association class III or IV)\r\n* Myocardial infarction within 12 months prior to starting study treatment\r\n* Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris
Serious cardiac condition within the last 6 months, such as uncontrolled arrhythmia, myocardial infarction, unstable angina or heart disease defined by the New York Heart Association (NYHA) Class III or Class IV
Myocardial infarction within 6 months of study initiation, active cardiac ischemia or New York Heart Association (NYHA) grade III or IV heart failure.
Patients with cardiovascular (CV) disease conditions including New York Heart Association class 3 or 4 congestive heart failure, unstable angina pectoris, or clinically important cardiac arrhythmias OR a recent (< 3 months) CV event, including myocardial infarction, unstable angina pectoris, or stroke.
Unstable cardiac disease as defined by one of the following:\r\n* Cardiac events such as myocardial infarction (MI) within the past 6 months\r\n* NYHA (New York Heart Association) heart failure class III-IV\r\n* Uncontrolled atrial fibrillation or hypertension
Has a history of cardiac event(s) (acute coronary syndrome, myocardial infarction, or ischemia) within 3 months of signing consent; subjects with a New York Heart Association classification of III or IV
New York Heart Association class III or IV cardiac disease or myocardial infarction within the past 12 months
Active angina or Class III or IV Congestive Heart Failure (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 6 months of the first dose of study drug, including myocardial infarction, unstable angina, Grade 2 or greater peripheral vascular disease, congestive heart failure, uncontrolled hypertension, or arrhythmias not controlled by medication
Significant cardiovascular disease with NYHA Class III or IV symptoms, or hypertrophic cardiomegaly, or restrictive cardiomegaly, or myocardial infarction within 6 months prior to enrollment, or unstable angina, or unstable arrhythmia.
Myocardial infarction within the last 12 months, severe/unstable angina, symptomatic congestive heart failure New York Heart Association (NYHA) class III or IV
Patients with any of the following:\r\n* History of myocardial infarction within six months\r\n* Unstable angina\r\n* Resting electrocardiogram (ECG) with clinically significant abnormal findings\r\n* New York Heart Association functional classification of III or IV
Patient has abnormal cardiac status, evidenced by any of the following:\r\n* New York Heart Association (NYHA) stage III or IV congestive heart failure (CHF)\r\n* Myocardial infarction within the previous 6 months\r\n* Symptomatic cardiac arrhythmia requiring treatment or persisting despite treatment
Cardiovascular disease that meets one of the following: congestive heart failure (New York Heart Association class III or IV), active angina pectoris, or recent myocardial infarction (within the last 6 months)
Cardiovascular disease that meets one of the following: congestive heart failure (New York Heart Association class III or IV), active angina pectoris, or recent myocardial infarction (within the last 6 months)
Cardiovascular disease that meets one of the following: congestive heart failure (New York Heart Association class III or IV), active angina pectoris, or recent myocardial infarction (within the last 6 months)
Cardiovascular disease that meets one of the following: congestive heart failure (New York Heart Association class III or IV), active angina pectoris, or recent myocardial infarction or acute coronary syndrome (within the last 6 months)
Patients must not have clinically significant illness including uncontrolled, active infection requiring intravenous antibiotics, New York Heart Association (NYHA) class III or class IV heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, or >= grade 3 cardiac arrhythmias
Serious medical illness, such as significant cardiac disease (e.g. symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmia, pericardial disease or New York Heart Association class III or IV), or severe debilitating pulmonary disease, that would potentially increase patients’ risk for toxicity
Patients with significant intercurrent medical illness (including New York Heart Association [NYHA] class III or IV heart disease, significant arrhythmias requiring medication, symptomatic coronary artery disease, myocardial infarction) within the previous 6 months
Patients must not have New York Heart Association class III or IV heart failure at the time of screening; patients must not have any thromboembolic event, unstable angina pectoris, myocardial infarction, or serious uncontrolled cardiac arrhythmia within 6 months prior to registration (Note: Patients with congenital long AT syndrome, congestive heart failure, frequent electrolyte abnormalities, and patients taking drugs known to prolong the QT interval may be at increased risk)
New York Heart Association Class III or IV (Appendix D) cardiac disease or myocardial infarction within the past 12 months before screening, or preexisting atrial fibrillation.
Clinically significant or uncontrolled cardiac disease including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, New York Heart Association Class III or IV congestive heart failure, circulatory collapse requiring vasopressor or inotropic support, or arrhythmia that requires therapy.
Myocardial infarction within 6 months of study initiation, active cardiac ischemia or New York Heart Association (NYHA) Grade III or IV heart failure
NYHA Class III-IV heart failure, myocardial infarction <6 months prior to study entry, and/or serious arrhythmia requiring anti-arrhythmic therapy
Cardiovascular disease that meets one of the following: congestive heart failure (New York Heart Association class III or IV), active angina pectoris, or recent myocardial infarction (within the last 6 months)
New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG.
Any serious medical condition that places the subject at an unacceptable risk if he or she participates in this study. Examples of such a medical condition are, but are not limited to, subject with unstable cardiac disease as defined by: cardiac events such as myocardial infarction (MI) within the past 6 months, NYHA (New York Heart Association) heart failure class III-IV, uncontrolled atrial fibrillation or hypertension; subjects with conditions requiring chronic steroid or immunosuppressive treatment, such as rheumatoid arthritis, multiple sclerosis and lupus, that likely need additional steroid or immunosuppressive treatments in addition to the study treatment
Myocardial infarction within 6 months of study initiation, active cardiac ischemia or New York Heart Association (NYHA) Grade III or IV heart failure.
Active angina or Class III or IV Congestive Heart Failure (CHF) (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 12 months of study enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, congestive heart failure, uncontrolled hypertension, or arrhythmias not controlled by outpatient medication
Other uncontrolled illness or medical condition, such as active infection, symptomatic heart failure (New York Heart Association class III or IV; moderate to severe objective evidence of cardiovascular disease), unstable angina pectoris, myocardial infarction or stroke within last 6 months, psychiatric illness that may limit compliance with study requirement or interfere with the understanding and giving of informed consent;
Myocardial infarction within 6 months of study initiation, active cardiac ischemia or New York Heart Association (NYHA) Grade III or IV heart failure
Any of the following within 6 months before randomisation: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft; congestive heart failure New York Heart Association (NYHA) Class III or IV.
Known cardiopulmonary disease defined as unstable angina, clinically significant arrhythmia, congestive heart failure (New York Heart Association [NYHA] Class III or IV) and/or myocardial infarction within 6 months prior to first dose, or severe pulmonary hypertension. As an example, well controlled atrial fibrillation would not be an exclusion whereas uncontrolled atrial fibrillation would be an exclusion.
Active grade III-IV cardiac failure as defined by the New York Heart Association criteria, uncontrolled angina or myocardial infarction (MI) within 6 months
Patients with any of the following: History of myocardial infarction within 6 months prior to starting treatment; Unstable angina; Resting electrocardiogram (ECG) with clinically significant abnormal findings; New York Heart Association functional classification of III or IV
Myocardial infarction within the last 12 months, severe/unstable angina, symptomatic congestive heart failure, New York Heart Association (NYHA) class III or IV
have 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.
Serious medical comorbidities such as New York Heart Association class III/IV cardiac disease, uncontrolled cardiac arrhythmias, myocardial infarction over the past 12 months
New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, or unstable arrhythmia.
Significant cardiovascular disease defined as:\r\n* Myocardial infarction within 6 months of screening\r\n* Unstable angina pectoris\r\n* Uncontrolled or clinically significant arrhythmia grade >= 2\r\n* Left ventricular ejection fraction (LVEF) below institutional limits at screening\r\n* Congestive heart failure New York Heart Association (NYHA) class III or IV\r\n* Presence of clinically significant valvular heart disease
Participants with any of the following:\r\n* History of myocardial infarction within six months\r\n* Unstable angina\r\n* New York Heart Association (NYHA) classification of III or IV
Subjects who have a history of major cardiac or neurologic disease including, but not limited to, angina pectoris, symptomatic coronary artery disease, uncontrolled hypertension (at time of study entry), New York Heart Association (NYHA) Class III or IV congestive heart failure, confirmed significant cardiac conduction abnormalities (including QTc > 0.45 sec) or arrhythmias, myocardial infarction within 12 months, cerebrovascular accidents, or transient ischemic attacks.
Cardiovascular disease that meets one of the following: congestive heart failure (New York Heart Association class III or IV), active angina pectoris, or recent myocardial infarction (within the last 6 months)
Significant cardiac disease as determined by the investigator including:\r\n* Known or suspected cardiac amyloidosis\r\n* Congestive heart failure of class III or IV of the New York Heart Association (NYHA) classification\r\n* Uncontrolled angina, hypertension or arrhythmia\r\n* Myocardial infarction in past 6 months\r\n* Any uncontrolled or severe cardiovascular disease\r\n* Prior cerebrovascular event with persistent neurologic deficit
Patient has clinically significant heart disease (such as uncontrolled angina, myocardial infarction within the last 3 months or congestive heart failure of New York Heart Association III or IV)
Active angina or Class III or IV Congestive Heart Failure (CHF) (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 12 months of the first dose of study drug, including myocardial infarction, unstable angina, Grade 2 or greater peripheral vascular disease, congestive heart failure, uncontrolled hypertension, or arrhythmias not controlled by outpatient medication
Any history of unstable angina, myocardial infarction, New York Heart Association (NYHA) class III or IV heart failure, and/or pulmonary hypertension
Patients with significant cardiac disease including heart failure that meets New York Heart Association (NYHA) class III and IV definitions, history of myocardial infarction within six months of study entry, uncontrolled dysrhythmias, or QTc greater than or equal to 450 msec
Has significant cardiovascular disease with New York Heart Association (NYHA) class III or IV symptoms, or hypertrophic cardiomegaly, or restrictive cardiomegaly, or myocardial infarction within 3 months prior to enrollment, or unstable angina, or unstable arrhythmia.
Patients with any of the following cardiac conditions:\r\n* Restrictive cardiomyopathy\r\n* Unstable angina within 6 months prior to enrollment\r\n* New York Heart Association functional class III-IV heart failure \r\n* Symptomatic pericardial effusion
New York(NY) Heart Association Class III or IV cardiac disease or Myocardial infarction within the past 12 months.
Cardiovascular disease that meets one of the following: congestive heart failure (New York Heart Association Class III or IV), active angina pectoris, or recent myocardial infarction (within the last 6 months).
History of myocardial infarction (MI) or congestive heart failure defined as Class II to IV per the New York Heart Association classification within 6 months of the first dose of ARQ 087 (MI occurring >6 months of the first dose of ARQ 087 will be permitted)
Significant cardiovascular disease defined as congestive heart failure (New York Heart Association class III or IV cardiac disease), angina pectoris requiring nitrate therapy or recent myocardial infarction (=< 6 months prior to registration)
Active heart disease including myocardial infarction within previous 6 months, symptomatic coronary artery disease, clinically significant arrhythmias not controlled by medication, atrial fibrillation (whether active or known past history), uncontrolled angina, or uncontrolled congestive heart failure (New York Heart Association Class III or IV).
Uncontrolled illnesses including symptomatic congestive heart failure (class III or IV as per New York Heart Association functional classification system), unstable angina pectoris, cardiac arrhythmia requiring therapy, myocardial infarction within the past 6 months, cardiac angioplasty or stenting within last 3 months, arterial or venous thrombi (including cerebrovascular accident), or active infection
Any of the following in previous 6 months: New York Heart Association (NYHA) class III/IV congestive heart failure, unstable angina, cerebrovascular accident (including transient ischemic attack), pulmonary embolism or myocardial infarction (by ECG or serologic criteria)
Have the presence of cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association (NYHA) Class III/IV congestive heart failure, or uncontrolled hypertension
Myocardial infarction (MI) or congestive heart failure defined as Class II to IV per the New York Heart Association (NYHA) classification within 6 months of the first dose of ARQ 087 (MI that occurred > 6 months prior to the first dose of ARQ 087 will be permitted)
The patient has a serious cardiac condition, such as congestive heart failure; New York Heart Association class II/ III/IV heart disease; unstable angina pectoris, cardiac stenting within 6 months of enrollment; myocardial infarction within the last 3 months; valvulopathy that is severe, moderate, or deemed clinically significant; or arrhythmias that are symptomatic or require treatment
Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months from day 1 of study administration, New York Heart Association class III or IV congestive heart failure, or symptomatic uncontrolled arrhythmias, prolonged corrected QT interval > 480 msec, treatment refractory hypertension, presence of a cardiac defibrillator
Patients with clinically significant cardiovascular disease: myocardial infarction or unstable angina pectoris within the last 6 months, class III/IV New York Heart Association (NYHA) heart failure
Significant cardiovascular disease (New York Heart Association class III or IV cardiac disease), myocardial infarction within the past 6 months, unstable angina, unstable arrhythmia or a need for anti-arrhythmic therapy (use of medication to control heart rate in patients with atrial fibrillation is allowed, if stable medication for at least last month prior to randomization and medication not listed as causing torsade de pointes), or evidence of acute ischemia on electrocardiogram (ECG)
Unstable angina, myocardial infarction or New York Heart Association (NYHA) class III/IV congestive heart failure within 30 days preceding study enrollment
New York Heart Assoc Class III or IV cardiac disease, myocardial infarction within the past 12 months before screening, or pre-existing atrial fibrillation.
Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, New York Heart Association Class II, III, or IV congestive heart failure, and arrhythmia requiring therapy.
History of unstable or newly diagnosed angina pectoris, recent myocardial infarction (within 6 months of enrollment), New York Heart Association Classification III or IV.
Abnormal cardiac function as manifested by NYHA (New York Heart Association) class III or IV heart failure or history of a prior myocardial infarction (MI) within the last five years prior to enrollment in the study
Any of the following cardiovascular conditions or values within 6 months before the first dose of study drug: myocardial infarction and the New York Heart Association (NYHA) class III or IV heart failure
History of cardiac disease: congestive heart failure defined as class II to IV per New York Heart Association (NYHA) classification; active coronary artery disease (CAD); previously diagnosed bradycardia or other cardiac arrhythmia defined as >= grade 2 according to NCI-CTCAE (version 4.0), or uncontrolled hypertension; myocardial infarction occurred within 6 months prior to study entry (myocardial infarction occurred > 6 months prior to study entry is permitted)
Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (New York Heart Association [NYHA] III-IV), and uncontrolled symptomatic arrhythmia
Have a history of New York Heart Association (NYHA) Class ?3, QTc interval > 480 milliseconds (ms) on screening electrocardiogram (ECG) per Friderica's formula, unstable angina, or myocardial infarction (MI) in 6 months prior to study drug administration.
Any of the following comorbid conditions:\r\n* New York Heart Association classification III or IV cardiovascular disease\r\n* Recent myocardial infarction (=< 30 days)\r\n* Uncontrolled infection
Patients with significant cardiovascular disease including congestive heart failure (New York Heart Association [NYHA] class III or IV), active angina pectoris or myocardial infarction within 6 months
Have a serious cardiac condition, such as congestive heart failure; New York Heart Association Class III/IV heart disease; unstable angina pectoris; myocardial infarction within the last 3 months; valvulopathy that is severe, moderate, or deemed clinically significant; or arrhythmias that are symptomatic or require treatment (not including participants with rate-controlled atrial fibrillation).
New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia
Cardiac risk factors including: \r\n* Patients experiencing cardiac event(s) (acute coronary syndrome, myocardial infarction, or ischemia) within 3 months of signing consent\r\n* Patients with a New York Heart Association classification of III or IV
Congestive heart failure (New York Heart Association Class III or IV), myocardial infarction within 12 months before starting study treatment, or unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris.
Presence of cardiac impairment defined as:\r\n* Prior history of cardiovascular disease including heart failure that meets New York Health Association (NYHA) class III and IV definitions; OR \r\n* History of myocardial infarction/active ischemic heart disease within one year of study entry; OR \r\n* Uncontrolled dysrhythmias; OR \r\n* Poorly controlled angina
Significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, congestive heart failure, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina) or significant pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months from day 1 of study drug administration, New York Heart Association class III or IV congestive heart failure, or symptomatic arrhythmias requiring therapy
Recent history (within 6 months of start of screening) of unstable angina pectoris pattern, myocardial infarction (including non-Q wave MI), or NYHA (New York Heart Association) Class III and IV Congestive Heart Failure (CHF)
Any severe concurrent disease or condition (including severe graft-versus-host disease, requirement for dialysis, symptomatic congestive heart failure [New York Heart Association Class III or IV], unstable angina pectoris, cardiac arrhythmia) which, in the judgment of the Investigator, would make the patient inappropriate for study participation.
The subject has a history of congestive heart failure, unstable angina, myocardial infarction, cardiac conduction abnormalities including Fridericia corrected QT interval (QTcF) prolongation of > 480 milliseconds (ms) or a pacemaker, clinically relevant impaired cardiovascular function (New York Heart Association (NYHA) class III/IV) or stroke within 3 months prior to enrollment.
New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG.
Uncontrolled hypertension, heart disease including history of congestive heart failure, history of myocardial infarction, angina pectoris requiring medication, clinically significant valvular heart disease, high risk arrhythmias, or disease corresponding to New York Heart Association class III or IV.
History of congestive heart failure defined as Class II to IV per New York Heart Association (NYHA) classification within 6 months prior to study entry; active coronary artery disease (CAD); clinically significant bradycardia or other uncontrolled, cardiac arrhythmia defined as greater than or equal to Grade 3 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), or uncontrolled hypertension; myocardial infarction occurring within 6 months prior to study entry (myocardial infarction occurring more than 6 months prior to study entry is permitted)
Active angina or Class III or IV Congestive Heart Failure (CHF) (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 12 months of study enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, congestive heart failure, uncontrolled hypertension, or arrhythmias not controlled by outpatient medication.
New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG
History of congestive heart failure defined as class II to IV per New York Heart Association (NYHA) classification; active coronary artery disease (CAD); clinically significant bradycardia (< 50 beats per minute [bpm]) or other uncontrolled, cardiac arrhythmia defined as >= grade 3 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, or uncontrolled hypertension (as determined by the investigator); myocardial infarction occurring within 6 months prior to study entry (myocardial infarction occurring > 6 months prior to study entry is permitted)
Those with New York Heart Association functional classification II, III or IV; active cardiac conditions including unstable coronary syndromes (unstable or severe angina, recent myocardial infarction), worsening or new-onset congestive heart failure, significant arrhythmias and severe valvular disease must be evaluated for risks of undergoing general anesthesia
Any of the following cardiovascular conditions or values within 6 months before the first dose of study drug:\r\n* A left-ventricular ejection fraction < 50%\r\n* Myocardial infarction within 2 years of randomization\r\n* New York Heart Association (NYHA) class III or IV heart failure
Any contraindications to vigorous exercise, including, but not limited to: brain metastases; current congestive heart failure (New York Heart Association class II, III or IV); serious or non-healing wound, ulcer, or bone fracture; spinal cord compromise or instrumentation due to metastatic disease; peripheral neuropathy >= grade 3; no serious cardiovascular events within 12 months including, but not limited to, transient ischemic attack (TIA), cerebrovascular accident (CVA), or myocardial infarction (MI)
Patients with clinically significant cardiac disease (e.g. congestive heart failure New York Heart Association class III or IV, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication), or myocardial infarction within the previous six months
Symptomatic or uncontrolled cardiovascular disease, myocardial infarction or severe/unstable angina within the past 6 months, or New York Heart Association class III or IV congestive heart failure
Any major cardiovascular event within 6 months of study initiation, including but not limited to myocardial infarction, unstable angina, cerebrovascular accident, pulmonary embolism, heart failure uncontrolled by medications or New York Heart Association class III or IV heart failure
Chronic ischemic heart disease with unstable angina, chronic heart failure at class III or IV, and myocardial infarction in the last 6 months
Cardiac dysfunction defined as: Myocardial infarction within six months of study entry, NYHA (New York Heart Association) Class II/III/IV heart failure, unstable angina, unstable cardiac arrhythmias
Medical illness unrelated to the tumor which in the opinion of the attending physician and principal investigator will preclude administration of the tracer\r\n* This includes patients with uncontrolled infection, chronic renal insufficiency, myocardial infarction within the past 6 months, unstable angina, cardiac arrhythmias other than chronic atrial fibrillation and chronic active or persistent hepatitis, or New York Heart Association Classification III or IV heart disease
Subject has any one of the following:\r\n* Clinically significant abnormal electrocardiography (ECG) finding at screening\r\n* Congestive heart failure (New York Heart Association class III or IV)\r\n* Myocardial infarction within 12 months prior to starting study treatment\r\n* Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris
Medical illness unrelated to the tumor which in the opinion of the attending physician and principal investigator will preclude administration of the agent; this includes patients with uncontrolled infection, chronic renal insufficiency, myocardial infarction within the past 6 months, unstable angina, cardiac arrhythmias other than chronic atrial fibrillation and chronic active or persistent hepatitis, or New York Heart Association classification III or IV heart disease
Medical illness unrelated to the tumor which in the opinion of the attending physician and principal investigator will preclude administration of the tracer; this includes patients with uncontrolled infection, chronic renal insufficiency, myocardial infarction within the past 6 months, unstable angina, cardiac arrhythmias other than chronic atrial fibrillation and chronic active or persistent hepatitis, or New York Heart Association Classification III or IV heart disease
Clinically significant heart disease (e.g., congestive heart failure of New York Heart Association class III or IV, angina not well controlled by medication, or myocardial infarction within 6 months)
Have 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.
The patient has active heart disease including myocardial infarction within previous 3 months, symptomatic coronary artery disease, arrhythmias not controlled by medication, unstable angina pectoris, or uncontrolled congestive heart failure (NYHA class III and IV)
Documented history of a cerebral vascular, unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association (NYHA) Class III-IV within 6 months prior to their first dose of study drug.
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
Patients who have experienced any of the following procedures or conditions currently or in the preceding 12 months: coronary artery bypass graft, vascular stent, myocardial infarction, angina pectoris, congestive heart failure New York Heart Association Grade ?2, supraventricular arrhythmias including atrial fibrillation, which are uncontrolled, haemorrhagic or thrombotic stroke, including transient ischaemic attacks or any other central nervous system bleeding.
Patients who have congestive heart failure (New York Heart Association [NYHA] class III or IV), sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block within the six months preceding enrollment
Clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:\r\n* Any history of myocardial infarction\r\n* Any history of clinically significant (as determined by the treating physician) atrial arrhythmia\r\n* Any history of ventricular arrhythmia\r\n* Any history of cerebrovascular accident or transient ischemic attack (TIA)\r\n* Any history of peripheral arterial occlusive disease requiring revascularization\r\n* Unstable angina within 6 months prior to enrollment\r\n* Congestive heart failure within 6 months prior to enrollment\r\n* Venous thromboembolism including deep venous thrombosis or pulmonary embolism within 6 months prior to enrollment\r\n* Unacceptable screening baseline cardiovascular assessment:\r\n** Baseline multi gated acquisition scan (MUGA) (to be done within 30 days of registration) or echocardiogram demonstrating left ventricular ejection fraction (LVEF) < 50 %\r\n** Corrected QT (QTc) >= 480 msec on screening electrocardiogram (ECG) (using the QTc Fridericia [QTcF] formula)
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
EXCLUSION - PROCUREMENT: Cardiac criteria: prolonged QT syndrome; atrial fibrillation/flutter; myocardial infarction within the last 12 months; cardiac echocardiography with left ventricular systolic function (LVSF) ? 30% or left ventricular ejection fraction (LVEF) ? 50%; cardiac dysfunction New York Heart Association (NYHA) III or IV; cardiac echocardiography with clinically significant pericardial effusion
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
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).
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)
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)
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
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
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
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 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
Not eligible for more intensive cytotoxic chemotherapy or consolidative autologous stem cell transplant based on one or more of the following:\r\n* Clinically significant heart or lung comorbidities, as reflected by at least 1 of the following:\r\n** Left ventricular ejection fraction (LVEF) =< 50%\r\n** Chronic stable angina or congestive heart failure controlled with medication\r\n** New York Heart Association (NYHA) class III or IV heart failure\r\n** Symptomatic chronic pulmonary disease or requirement for intermittent or continuous oxygen therapy\r\n* Presence of other medical comorbidity or limitation in functional status which the investigator judges to be incompatible with an acceptable risk to the subject with the use of intensive chemotherapy; the associated comorbidity or functional limitation must be clearly documented in the medical record at the time of enrollment OR
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).
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.
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
Patients who are medically unstable, patients who are seriously or terminally ill, and patients whose clinical course is unpredictable; for example:\r\n* Patients on life support or in a critical care unit\r\n* Patients with unstable occlusive disease (e.g., crescendo angina)\r\n* Patients with clinically unstable cardiac arrhythmias, such as recurrent ventricular tachycardia\r\n* Patients with uncontrolled congestive heart failure (New York heart Association [NYHA] class IV)
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.
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)
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
Evidence of significant cardiovascular disease including history of recent (< 6 months prior) myocardial infarction, congestive heart failure, primary cardiac arrhythmias (not due to electrolyte disorder or drug toxicity, for example) beyond occasional premature ventricular contractions (PVC's), angina, positive low-level stress test, or cerebrovascular accident; all patients should have baseline pulmonary function tests; adequate pulmonary function should be documented (forced expiratory volume-one second [FEV1] > 2 liters or >= 75% of predicted for height and age) prior to initiating therapy
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)
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
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
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
Cardiac:\r\n* History of clinically significant cardiac dysfunction, including the following:\r\n** Current unstable angina\r\n** Current symptomatic congestive heart failure of New York Heart Association (NYHA) class 2 or higher\r\n** History of congenital long QT syndrome or mean corrected QT Fridericia’s formula (QTcF) > 450 msec at baseline or uncorrectable electrolyte abnormalities\r\n** Uncontrolled hypertension >= grade 3 (patients with a history of hypertension controlled with anti-hypertensives to =< grade 1 and patients with hypertension grade 2 that have treating physician approval of safety, are eligible)\r\n** Left ventricular ejection fraction (LVEF) below institutional lower limit of normal (LLN) or below 40%, whichever is lower\r\n** Uncontrolled arrhythmias\r\n** Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack within the previous 6 months \r\nNote: Optional tumor biopsies (punch, fine-needle aspiration [FNA], core or excisional) at pre-treatment, week 1, and at progression will be presented to subjects considering this study; additional optional tumor biopsies may also be offered if deemed appropriate by principal investigator; additional subjects at the MTD/RP2D expansion cohort are required to have correlative studies (blood collection and tumor biopsies at the defined time points)
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)
Clinically significant cardiovascular disease, including but not limited to, acute myocardial infarction within 6 months prior to enrollment, severe/unstable angina pectoris or coronary artery bypass grafting, New York Heart Association Class III/IV congestive heart failure, ventricular arrhythmias requiring treatment or left ventricular ejection fraction (LVEF) < 50%;
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.
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
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 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
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
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)
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
History of significant cardiac disease, particularly uncompensated congestive heart failure New York Heart Association (NYHA) grade 2 or more or left ventricular ejection fraction (LVEF) < 40% on any prior assessment; (assessment of LVEF prior to therapy is not required in the absence of other clinical indicators of heart disease); patients with a prior LVEF < 40% will require-evaluation prior to study entry
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
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
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)
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).
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)
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 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)
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
Patients with a significant history of cardiovascular disease or procedures within the preceding 6 months (e.g., myocardial infarction [MI], coronary artery bypass graft placement, angioplasty, vascular stent, angina pectoris, ventricular arrhythmias requiring continuous therapy, congestive heart failure New York Heart Association [NYHA] grade >= 2, thrombotic or thromboembolic event)
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
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
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
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 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).
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
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
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%.
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.
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
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
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
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
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
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
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
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
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
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
Significant cardiac disease:\r\n* Congestive heart failure > class II New York Heart Association (NYHA)\r\n* Myocardial infarction within 6 months prior to study entry\r\n* Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin\r\n* Serious myocardial dysfunction, defined as scintigraphically (multi gated acquisition scan [MUGA], myocardial scintigram) or echocardiogram determined absolute left ventricular ejection fraction (LVEF) below normal (< 50%)
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
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
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
Patients with any of the following:\r\n* History of myocardial infarction within six months\r\n* Patients with corrected QT (QTc) prolongation > 500 msec or other significant electrocardiogram (ECG) abnormality noted within 14 days of treatment\r\n** For patients enrolled in the Phase 1-T portion of the protocol, the QTc should not exceed 470 msec\r\n* New York Heart Association (NYHA) classification of III or IV\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\r\n* Condition requiring concurrent use of drugs or biologics with pro-arrhythmic potential
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
History of clinically significant cardiac dysfunction, including the following:\r\n* Current unstable angina\r\n* Symptomatic congestive heart failure of New York Heart Association (NYHA) class 2 or higher \r\n* History of congenital long QT syndrome or mean QT interval using the Fridericia correction formula (QTcF) > 450 msec at baseline or uncorrectable electrolyte abnormalities\r\n* Uncontrolled hypertension >= grade 2 (patients with a history hypertension controlled with anti-hypertensives to =< grade 1 are eligible)\r\n* Patients with left ventricular ejection fraction (LVEF) as measured by echocardiogram or multiple gated acquisition (MUGA) scan below institutional lower limit of normal or below 50%, whichever is lower, will be excluded from the study\r\n* Uncontrolled arrhythmias\r\n* Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack within the previous 6 months
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
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
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.
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).
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)
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 QTc > 480 msec at baseline\r\n* Symptomatic congestive heart failure (CHF) of New York Heart Association (NYHA) functional class >= 3\r\n* Major conduction abnormality (unless a cardiac pacemaker is present)
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)
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
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
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
Patients who are clinically unstable, patients who are seriously or terminally ill with a life expectancy of less than 1 month, and patients whose clinical course are unpredictable; for example:\r\n* Patients on life support or in a critical care unit\r\n* Patients with unstable occlusive disease (e.g., crescendo angina)\r\n* Patients with clinically unstable cardiac arrhythmias, such as recurrent ventricular tachycardia\r\n* Patients with uncontrolled congestive heart failure (New York Heart Association [NYHA] class IV)\r\n* Patients with recent cerebral hemorrhage\r\n* Patients who have undergone surgery within 24 hours prior to the study sonographic examination
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
PATIENT: Patients who are medically unstable, patients who are seriously or terminally ill, and patients whose clinical course is unpredictable; for example:\r\n* Patients on life support or in a critical care unit\r\n* Patients with unstable occlusive disease (e.g., crescendo angina)\r\n* Patients with clinically unstable cardiac arrhythmias, such as recurrent ventricular tachycardia\r\n* Patients with uncontrolled congestive heart failure (New York Heart Association [NYHA] class IV)\r\n* Patients with recent cerebral hemorrhage\r\n* Patients who have undergone surgery within 24 hours prior to the study sonographic examination
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
Patients who are medically unstable, patients who are seriously or terminally ill, and patients whose clinical course is unpredictable; for example:\r\n* Patients on life support or in a critical care unit\r\n* Patients with unstable occlusive disease (eg, crescendo angina)\r\n* Patients with clinically unstable cardiac arrhythmias, such as recurrent ventricular tachycardia\r\n* Patients with uncontrolled congestive heart failure (New York Heart Association [NYHA] class IV)
Patients may not have New York Heart Association (NYHA) class III or IV congestive heart failure or left ventricular ejection fraction (LVEF) < 50%; patients with a corrected QT (QTc) > 470 ms, a family history of long QT syndrome, and those on medications known to cause Torsades de Pointes will be excluded from the study