Severe pulmonary, cardiac or other systemic disease, specifically:
Current symptomatic pulmonary embolism
Prior or concurrent pulmonary embolism
Pulmonary embolism within 30 days prior to study entry
Pulmonary embolism
Pulmonary hypertension
The patient has uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, pulmonary hypertension) that, in the Investigator's opinion, would put the patient at significant risk for pulmonary complications during the study.
Other cardiac or pulmonary disease that, at the investigator’s discretion, can impair treatment safety
Significant pulmonary disease or condition
Severe pulmonary hypertension (PHT) (on echo or right side cardiac catheterization);
Significant pulmonary disease, including pulmonary hypertension or interstitial pneumonitis
The patient has idiopathic pulmonary fibrosis (IPF) as documented in their medical history.
Any significant medical condition, including any suggested by screening laboratory findings that, in the opinion of the investigator or sponsor, may place the subject at undue risk from the study, including but not necessarily limited to uncontrolled hypertension and/or diabetes, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease requiring hospitalization within 3 months) or neurological disorder (e.g., seizure disorder active within 3 months).
Symptomatic pulmonary embolism within 6 months prior to study entry
Significant pulmonary disease or condition
Severe pulmonary disease (despite above oxygen saturation and DLCO) including severe and uncontrolled asthma (per 2007 National Heart, Lung, and Blood Institute [NHLBI] Guidelines for the Diagnosis and Treatment of Asthma Expert Panel Report 3), chronic obstructive pulmonary disease, and/or pulmonary hypertension (PH); a diagnosis of PH will be made by finding of mean pulmonary artery pressure (mPAP) < 25 mm Hg on right heart catherization; in patients unable and/or unwilling to undergo cardiac catheterization, patients will be excluded with the following constellation of findings based upon presumptive diagnosis of PH (positive predictive value [PPV] of 62%): TRJ velocity > 2.5 m/sec AND either N-terminal pro-brain natriuretic peptide (NT-pro-BNP) >= 160 pg/ml OR 6-minute walk distance < 333 m
Any known uncontrolled cardiovascular disease, pulmonary embolism, hypertension not adequately controlled by standard medications within 3 months prior to enrollment.
Patients with severe emphysema, pulmonary vasculitis, or a history of pulmonary emboli
Severe pulmonary hypertension (PHT) (on echo or right side cardiac catheterization)
Uncontrolled, clinically significant pulmonary disease (for example, chronic obstructive pulmonary disease, pulmonary hypertension, idiopathic pulmonary fibrosis) that in the opinion of the investigator would put the participant at significant risk for pulmonary complications during the study
Significant pulmonary artery hypertension (PAH) defined as:\r\n* Peak systolic pulmonary artery pressure > 50 mmHg by resting echocardiogram will require right heart catheterization; if pulmonary artery pressure (PAP) is not evaluable on echocardiogram due to lack of a Tricuspid regurgitant jet, then normal anatomy and function as evidenced by normal right atrium and ventricle size, shape and wall thickness and septum shape must be documented to rule-out PAH; otherwise, right heart catheterization is indicated; prior history of PAH but controlled with medications will not exclude patients from the protocol; PAH is considered controlled with medications if peak systolic pulmonary artery pressure is < 45 mmHg or mean pulmonary artery pressure by right heart catheterization is < 30 mmHg at rest\r\n* Mean pulmonary artery pressure by right heart catheterization exceeding 30 mmHg at rest; if mean PAP is elevated and pulmonary vascular resistance and transpulmonary gradient are normal then the patient is eligible for the protocol\r\n* New York Heart Association (NYHA)/World Health Organization Class III or IV
Pulmonary embolism.
Pulmonary hypertension.
Presence of cavitation of central pulmonary lesion
Pulmonary conditions such as sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or hypersensitivity pneumonitis are excluded
Anuria, dehydration, severe pulmonary congestion or pulmonary edema or fixed low cardiac input
Treated with appropriate maximal medical therapy for pulmonary toxicity
use of systemic steroids or immunosuppressive medication Pulmonary hypertension will not be an exclusion criterion as patients with pulmonary hypertension were shown to have higher bursting pressures following PA sealing in previous studies.
No prior history of idiopathic pulmonary fibrosis
Patient has severe pulmonary, cardiac, or other systemic disease, specifically:
No cardiomegaly or bilateral pulmonary infiltrates on chest radiograph; patients may have pulmonary metastatic lesions
ELIGIBILITY CRITERIA- LYMPHODEPLETION/INFUSION OF tvs-CTL: No cardiomegaly or bilateral pulmonary infiltrates on chest radiograph; patients may have pulmonary metastatic lesions
Subjects with a history of pulmonary embolism are excluded
Subjects with a history of pulmonary hypertension is excluded
Pulmonary embolism
Pulmonary conditions such as sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or hypersensitivity pneumonitis
Presence of leukemic or infectious pulmonary parenchymal disease
No overt cardiac, gastrointestinal, pulmonary or psychiatric disease
Has a history of blood clots, pulmonary embolism, or DVT unless controlled by anticoagulant treatment
known pneumonitis or pulmonary fibrosis with clinically significant impairment of pulmonary function
Clinically no evidence of pulmonary disease
Evidence of pulmonary insufficiency
Other cardiac or pulmonary disease that, at the investigators discretion, can impair treatment safety
Patients must have no overt cardiac, gastrointestinal, pulmonary or psychiatric disease
Chronic pulmonary aspergillosis, pulmonary sarcoidosis, aspergilloma, or allergic bronchopulmonary aspergillosis (ABPA).
Symptomatic pulmonary KS
Clinical evidence of pulmonary insufficiency
Patients with radiographic changes including pulmonary disease, including but not limited to: pulmonary nodules, infiltrates, pleural effusion are excluded unless cleared by pulmonary biopsy showing no evidence for pulmonary infection
No overt cardiac, gastrointestinal, pulmonary or psychiatric disease
Pulmonary hypertension moderate to severe by echocardiographic standards
Significant pulmonary disease or condition
History of pulmonary disease or abnormal pulmonary function studies
Pulmonary metastases
Pulmonary conditions such as sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or hypersensitivity pneumonitis
Uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease [COPD], pulmonary hypertension) that in the opinion of the investigator would put the patient at significant risk for pulmonary complications during the study
Known history of pulmonary fibrosis
Pulmonary nodules > 10 mm\r\n* Pulmonary nodules > 10 mm that have been stable for > 6 months and are not clearly metastatic disease per the treating investigator are permitted
Significant pulmonary disease, including pulmonary hypertension or interstitial pneumonitis
History of pulmonary hypertension
Pulmonary embolism
Pulmonary hypertension
History or other evidence of chronic pulmonary disease associated with functional limitation
History or other evidence of chronic pulmonary disease associated with functional limitation
Any significant medical condition, including any suggested by screening laboratory findings that, in the opinion of the investigator or sponsor, may place the subject at undue risk from the study, including but not necessarily limited to uncontrolled hypertension and/or diabetes, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease requiring hospitalization within 6 months) or neurological disorder (e.g., seizure disorder active within 6 months)
Previous history of pulmonary embolism or pulmonary embolism found on screening exam.
The patient has uncontrolled, clinically significant pulmonary disease (e.g., COPD, pulmonary hypertension) that in the opinion of the investigator would put the patient at significant risk for pulmonary complications during the study.
Pulmonary LCNEC;
Stable cardiovascular, pulmonary health status
Normal clinical assessment of pulmonary function
Any other serious cardiac illness or medical conditions such as unstable angina, pulmonary embolism, or uncontrolled hypertension.
Any other serious cardiac illness or medical conditions such as unstable angina, pulmonary embolism, or uncontrolled hypertension
Pulmonary embolism.
Pulmonary hypertension.
Pulmonary embolism within 12 months before screening
Participant has pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen.
Uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, pulmonary hypertension) that in the opinion of the Investigator would put the patient at significant risk for pulmonary complications during the study.
Significant pulmonary disease, including pulmonary hypertension or interstitial pneumonitis
Known history of pulmonary hypertension
Anuria, dehydration, severe pulmonary congestion or pulmonary edema or fixed low cardiac input since all are conditions for which osmotic diuresis are contraindicated and ascorbic acid has high osmolarity
Pulmonary disease including or greater than grade 2 dyspnea or laryngeal edema, grade 3 pulmonary edema or pulmonary hypertension according to CTCAE 4.03
Pulmonary hypertension
Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring the use of oxygen
Patients with known pulmonary hypertension
Pulmonary embolism on active therapy
Patients with severe pulmonary hypertension \r\n* Tricuspid jet velocity > 2.5 m/sec
Symptomatic pulmonary disease currently requiring regular medication including but not restricted to bronchodilators
Moderate or severe pulmonary hypertension defined as pulmonary artery systolic pressure (PASP) > 50mm Hg; for those patients where PASP is indeterminate, moderate to severe symptoms of pulmonary hypertension (World Health Organization functional assessment class III or IV) will be used to determine exclusion criteria
>2 unilateral pulmonary metastasis
Patients with compromised pulmonary disease.
DONOR: Significant pulmonary disease
Patients with idiopathic pulmonary fibrosis
Pulmonary:
Previous history of pulmonary embolism or pulmonary embolism found on screening exam.
Ineligible for curative pulmonary metastasectomy
Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring the use of oxygen
Any history or signs of pulmonary lymphangitic spread;
Previous pulmonary embolism within 12 months before study entry
Known pulmonary hypertension of any severity.
Previous pulmonary embolism within 12 months prior to study entry
Prior history of pulmonary fibrosis.
Significant pulmonary compromise
Clinical Pulmonary Infection Score (CPIS) of at least 6
History of symptomatic pulmonary disease or non-malignant pulmonary disease requiring treatment.
The patient has uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, pulmonary hypertension) that in the opinion of the Investigator would put the patient at significant risk for pulmonary complications during the study.
Pulmonary: new onset hypoxia
Echocardiographic evidence of pulmonary hypertension.
Pulmonary hypertension,
No symptomatic cardiac or pulmonary disease and a performance status equal to or =< 2
Known pulmonary hypertension
Pulmonary embolism (PE) within the last 6 months prior to registration
Uncontrolled cardiac or pulmonary disease
Active or uncontrolled pulmonary disease
Acute pulmonary embolus or pulmonary infarction in the last week
Diagnosis of acute pulmonary embolism within past 2 weeks
Diagnosis of pulmonary hypertension
Participant has had pulmonary embolism or any other thrombo-embolic event within 6 months prior to study entry
Diagnosis of acute pulmonary embolism within past 2 weeks
Diagnosis of pulmonary hypertension
Patients with pulmonary edema, congestive heart failure or pulmonary embolus
severe pulmonary hypertension
Severe pulmonary hypertension
CONTROL (HEALTHY) GROUP: Severe pulmonary hypertension
Participant has ever experienced one or more hepatic decompensation events or a history of decompensated liver disease as listed below:\r\n* Clinical ascites\r\n* Variceal bleeding documented by endoscopy\r\n* Spontaneous bacterial peritonitis documented by positive culture\r\n* Hepatic encephalopathy\r\n* Hepatorenal syndrome (type 1 or 2)\r\n* Porto-pulmonary hypertension\r\n* Hepato-pulmonary hypertension\r\n* Any liver-related event which led to a hospitalization or a grade 4 event
Active pulmonary disease requiring medication to include multiple inhalers
acute pulmonary embolism or pulmonary infarction,
Patients with pulmonary hypertension or unstable cardiopulmonary conditions
Known pulmonary hypertension
Patients with pulmonary hypertension or unstable cardiopulmonary conditions
Patients with severe emphysema, pulmonary vasculitis, or a history of pulmonary emboli
Patients with evidence of moderate or severe pulmonary hypertension on echocardiogram
Suspected pulmonary hypertension: additional testing required, such as echocardiogram
Moderate-to-severe pulmonary fibrosis
PATIENT: Patients with severe emphysema, pulmonary vasculitis, pulmonary hypertension or a history of pulmonary emboli
Patients with severe emphysema, pulmonary vasculitis, pulmonary hypertension, respiratory distress syndrome, or a history of pulmonary embolism.
Patients with uncontrollable emphysema, pulmonary vasculitis, pulmonary hypertension or a history of pulmonary emboli
Severe emphysema, pulmonary emboli, or other conditions that cause pulmonary hypertension due to compromised pulmonary-arterial vasculature
Patients who have a known cardiac shunt or pulmonary hypertension
Patients with known pulmonary hypertension
Patients with severe emphysema, pulmonary vasculitis, or a history of pulmonary emboli
Patients with severe emphysema, pulmonary vasculitis, or a history of pulmonary emboli
With significant heart or pulmonary disease.
Impaired cardiac function including any of the following:\r\n* Myocardial infarction within 6 months of starting study drug\r\n* Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an anti-hypertensive regimen)
A past medical history of other clinically significant cardiovascular disease (eg, uncontrolled hypertension, history of labile hypertension, history of poor compliance with an antihypertensive regimen).
Impaired cardiac function including any of the following:\r\n* Myocardial infarction within 6 months of starting study drug\r\n* A past medical history of clinically significant electrocardiography (ECG) abnormalities, including corrected QT (QTc) 481 ms or greater\r\n* Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
EXCLUSION - PARTICIPANT: Clinically significant cardiac disease or impaired cardiac function, including any of the following: \r\n* Clinically significant and/or uncontrolled heart disease such as congestive heart failure (New York Heart Association grade >= 2) uncontrolled hypertension, or clinically significant arrhythmia currently requiring medical treatment\r\n* Fridericia's correction formula (QTcF) > 470 msec for females, or > 450 msec for males, on screening electrocardiography (ECG) or congenital long QT syndrome\r\n* Acute myocardial infarction or unstable angina pectoris < 6 months prior to screening
Known impaired cardiac function including any of the following:\r\n* History or presence of clinically significant ventricular or atrial tachyarrhythmias;\r\n* Clinically significant resting bradycardia (< 50 beats per minute);\r\n* Myocardial infarction within 1 year of starting study drug;\r\n* Other clinically significant heart disease (e.g., unstable angina, congestive heart failure, or uncontrolled hypertension)
Cardiovascular disorders such as:\r\n* Inability to monitor the QT interval on electrocardiogram (ECG)\r\n* Complete left bundle branch block\r\n* Right bundle branch block plus left anterior or posterior hemiblock\r\n* Use of a ventricular-paced pacemaker\r\n* Congenital long QT syndrome or a known family history of long QT syndrome\r\n* Clinically significant resting bradycardia (< 50 beats per minute)\r\n* Corrected QT interval (QTc) > 450 msec on baseline ECG; if QTc > 450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc\r\n* Myocardial infarction within 6 months prior to starting study\r\n* History of unstable angina within 6 months prior to study entry\r\n* Other clinically significant uncontrolled heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension)\r\n* History of or presence of clinically significant ventricular or atrial tachyarrhythmias
Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:\r\n* History or presence of sustained ventricular tachyarrhythmia; (patients with a history of atrial arrhythmia are eligible but should be discussed with Novartis prior to enrollment)\r\n* Any history of ventricular fibrillation or torsade de pointes\r\n* Bradycardia defined as heart rate (HR) < 50 beats per minute (bpm); patients with pacemakers are eligible if HR >= 50 bpm\r\n* Screening electrocardiogram (ECG) with a corrected QT (QTc) > 470 msec\r\n* Right bundle branch block + left anterior hemiblock (bifascicular block)\r\n* Patients with myocardial infarction or unstable angina =< 12 months prior to starting study drug\r\n* Other clinically significant heart disease (e.g., congestive heart failure [CHF] New York [NY] Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
Impaired cardiac function or clinically significant cardiac diseases, including any one of the following: \r\n* History or presence of sustained ventricular tachyarrhythmia; (patients with a history of atrial arrhythmia are eligible but should be discussed with Novartis prior to enrollment)\r\n* Any history of ventricular fibrillation or torsade de pointes\r\n* Bradycardia defined as heart rate (HR) < 50 beats per minute (bpm); patients with pacemakers are eligible if HR >= 50 bpm\r\n* Screening electrocardiogram (ECG) with a corrected QT (QTc) > 470 msec\r\n* Right bundle branch block + left anterior hemiblock (bifascicular block)\r\n* Myocardial infarction or unstable angina =< 12 months prior to starting study drug\r\n* Other clinically significant heart disease (e.g., congestive heart failure [CHF] New York [NY] Heart Association class III or IV , uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
Impaired cardiac function or clinically significant heart disease, including any one of the following:\r\n* Angina pectoris within 3 months\r\n* Acute myocardial infarction within 3 months\r\n* Corrected QT interval (QTc) > 480 msec on the screening electrocardiogram (ECG)\r\n* A past medical history of clinically significant ECG abnormalities\r\n* Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
Impaired cardiac function or clinically significant cardiac diseases, including any of the following: history or presence of ventricular tachyarrhythmia; presence of unstable atrial fibrillation (ventricular response > 100 beats per minute [bpm]); patients with stable atrial fibrillation are eligible, provided they do not meet any of the other cardiac exclusion criteria; clinically significant resting bradycardia (< 50 bpm); angina pectoris or acute myocardial infarction =< 3 months prior to starting study drug; other clinically significant heart disease (e.g., symptomatic congestive heart failure; uncontrolled arrhythmia or hypertension; history of labile hypertension or poor compliance with an antihypertensive regimen)
Impaired cardiac function or clinically significant heart disease, including any one of the following:\r\n* Angina pectoris within 3 months\r\n* Acute myocardial infarction within 3 months\r\n* Fridericia QT (QTcF) > 450 msec for males and > 470 msec for females on the screening electrocardiogram (ECG)\r\n* A past medical history of clinically significant ECG abnormalities or a family history of prolonged QT-interval syndrome\r\n* Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
Impaired cardiac function including any of the following: Screening ECG with a QTc >450 msec. The QTc interval will be calculated by Fridericia's correction factor (QTcF) at Screening and on Day 5 prior to the first dose of AC220. The QTcF will be derived from the average QTcF in triplicate.; If QTcF>450 msec on Day 5, AC220 will not be given; Patients with congenital long QT syndrome; History or presence of sustained ventricular tachycardia requiring medical intervention; Any history of clinically significant ventricular fibrillation or torsades de pointes; Known history of second or third degree heart block (may be eligible if the patient currently has a pacemaker); Sustained heart rate of <50/minute on pre-entry ECG; Right bundle branch block + left anterior hemiblock (bifascicular block); Patients with myocardial infarction or unstable angina within 6 months prior to starting study drug; CHF NY Heart Association class III or IV.
Patient has a history or current evidence of clinically significant heart disease including:\r\n* Clinically significant congestive heart failure, unstable angina pectoris\r\n* Clinically significant cardiac arrhythmia\r\n* Myocardial infarction during the last 6 months, and/or a current electrocardiogram (ECG) tracing that is abnormal in the opinion of the treating Investigator\r\n* Corrected QT interval (QTc) prolongation > 480 msec (Bazett's formula)\r\n* Congenitally long QT syndrome, and/or current anti-arrhythmic therapy, and / or has received any marketed or experimental compound in the last 1 week prior to entering the study with known effects of QT prolongation
Uncontrolled intercurrent illnesses including, but not limited to unstable angina or uncontrolled cardiac arrhythmia, chronic liver disease, complete left bundle branch block, obligate use of a cardiac pacemaker, ST depression of > 1 mm in two or more leads and/or T wave inversions in two or more contiguous leads, congenital long QT syndrome, history of or presence of significant ventricular or atrial tachyarrhythmias, clinically significant resting bradycardia (< 50 beats per minute), corrected QT (QTc) > 480 ms on screening electrocardiogram that could jeopardize the patient’s ability to receive the chemotherapy described in the protocol safely
Impaired cardiac function including any one of the following:\r\n* Inability to monitor the QT interval on electrocardiogram (ECG)\r\n* Congenital long QT syndrome or a known family history of long QT syndrome\r\n* Clinically significant resting brachycardia (< 50 beats per minute)\r\n* QTc > 450 msec on baseline ECG; if QTc > 450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc\r\n* Myocardial infarction within 12 months prior to starting study\r\n* Other clinically significant uncontrolled heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension)\r\n* History of or presence of clinically significant ventricular or atrial tachyarrhythmias
A past medical history of other clinically significant cardiovascular disease - e.g., uncontrolled hypertension, history of labile hypertension or history of poor compliance with an antihypertensive regimen
Impaired cardiac function or clinically significant cardiac diseases, including any one of the following: \r\n* History or presence of sustained ventricular tachyarrhythmia; (patients with a history of atrial arrhythmia are eligible) \r\n* Any history of ventricular fibrillation or torsade de pointes \r\n* Bradycardia defined as heart rate (HR) < 50 beats per minute (bpm); patients with pacemakers are eligible if HR >= 50 bpm\r\n* Screening electrocardiogram (ECG) with a Fridericia's correction formula (QTcF) > 450 msec (QTcF = QT/^3 square root of RR); if potassium, magnesium, or calcium blood levels are below normal limits, consider repeating ECG after correction of these electrolytes\r\n* Right bundle branch block + left anterior hemiblock (bifascicular block) \r\n* Patients with myocardial infarction or unstable angina =< 6 months prior to starting study drug \r\n* Other clinically significant heart disease (e.g., congestive heart failure [CHF] New York [NY] Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
Impaired cardiac function including any of the following:\r\n* Congenital long QT syndrome or a known family history of long QT syndrome;\r\n* Corrected QT (QTc) > 450 msec;\r\n* History or presence of clinically significant ventricular or atrial tachyarrhythmias;\r\n* Clinically significant resting bradycardia (< 50 beats per minute); \r\n* Myocardial infarction within 1 year of starting study drug;\r\n* Other clinically significant heart disease (e.g., unstable angina, congestive heart failure, or uncontrolled hypertension)
Impaired cardiac function including any of the following:\r\n* Congenital long QT syndrome or a known family history of long QT syndrome\r\n* History or presence of clinically significant ventricular or atrial tachyarrhythmias\r\n* Clinically significant resting bradycardia (< 50 beats per minute)\r\n* Inability to monitor the QT interval by electrocardiogram (ECG)\r\n* Corrected QT (QTc) > 450 msec on baseline ECG; if QTc > 450 and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc\r\n* Myocardial infarction within 1 year of starting study drug\r\n* Other clinically significant heart disease (e.g., unstable angina, congestive heart failure, or uncontrolled hypertension)
Impaired cardiac function or clinically significant cardiac diseases, history of arrhythmia (including ventricular fibrillation or torsade de pointes), bradycardia < 50 beats per minute (bpm), screening electrocardiogram (ECG) with prolonged corrected QT (QTc) (> 450 msec), uncontrolled hypertension or any history or presence of sustained ventricular tachyarrhythmia
Impaired cardiac function including any of the following:\r\n* Myocardial infarction within 6 months of starting study drug;\r\n* A past medical history of clinically significant ECG abnormalities\r\n* Other clinically significant heart disease (e.g. uncontrolled congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an anti-hypertensive regimen)
Impaired cardiac function including any of the following:\r\n* Inability to monitor the QT interval on electrocardiogram (ECG)\r\n* Congenital long QT syndrome or a known family history of long QT syndrome\r\n* Clinically significant resting brachycardia (< 50 beats per minute)\r\n* Corrected QT (QTc) > 450 msec on baseline ECG; NOTE: if the ECG shows a QTc interval greater than 450 msecs at screening triplicates should be performed, one minute apart to confirm the finding (after replacement of any electrolyte imbalance); if 2/3 or 3/3 of the ECGs confirm the QT prolongation (i.e. QTc interval > 450 msecs) the patient must not be included into the trial\r\n* Myocardial infarction =< 3 months prior to starting study\r\n* Other clinically significant uncontrolled heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension) \r\n* History of or presence of clinically significant ventricular, atrial tachyarrhythmias or ejection fraction cutoff\r\n* Left ventricle ejection fraction < 45%\r\n* History of congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
Impaired cardiac function or clinically significant heart disease, including any one of the following: a) angina pectoris within 3 months; b) acute myocardial infarction within 3 months; c) QT interval corrected with the Fridericia formula (QTcF) greater than 450 msec for males and greater than 470 msec for females on the screening electrocardiogram (ECG); d) a past medical history of clinically significant ECG abnormalities or a family history of prolonged QT-interval syndrome; e) other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
Impaired cardiac function or clinically significant heart disease, including any one of the following:\r\n* Angina pectoris within 3 months\r\n* Acute myocardial infarction within 3 months\r\n* Corrected Fridericia's QT (QTcF) > 450 msec for males and > 470 msec for females on the screening electrocardiogram (ECG)\r\n* A past medical history of clinically significant ECG abnormalities or a family history of prolonged QT-interval syndrome\r\n* New York Heart Association classification IV cardiovascular disease or symptomatic class III disease \r\n* Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
Known significant cardiac abnormalities, including:\r\n* History or presence of sustained ventricular tachyarrhythmia (participants with a history of atrial arrhythmia are eligible but should be discussed with Dr. Laubach prior to enrollment)\r\n* Any history of ventricular fibrillation or torsades de pointes\r\n* Bradycardia defined as heart rate (HR) < 50 beats per minute (bpm); participants with pacemakers are eligible if HR >= 50 bpm\r\n* QTcF interval >= 450 milliseconds on screening electrocardiogram (ECG);\r\n* Right bundle branch block + left anterior hemiblock (bifascicular block)\r\n* Participants with myocardial infarction or unstable angina =< 6 months prior to starting study drug\r\n* Other clinically significant heart disease (e.g. congestive heart failure [CHF] New York [NY] Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
Impaired cardiac function or clinically significant cardiac diseases, including any of the following:\r\n* History or presence of ventricular tachyarrhythmia\r\n* Presence of unstable atrial fibrillation (ventricular response > 100 bpm) (NOTE: patients with stable atrial fibrillation are eligible, provided they do not meet any of the other cardiac exclusion criteria)\r\n* Clinically significant resting bradycardia (< 50 bpm)\r\n* Angina pectoris or acute myocardial infarction =< 3 months prior to registration\r\n* Other clinically significant heart disease (e.g., symptomatic congestive heart failure; uncontrolled arrhythmia or hypertension; history of labile hypertension or poor compliance with an antihypertensive regimen)
Impaired cardiac function including any of the following:\r\n* Screening electrocardiogram (ECG) with a corrected QT interval (QTc) > 450 msec \r\n* Bradycardia defined as heart rate (HR) < 50 beats per minute (bpm)\r\n* Right bundle branch block + left anterior hemiblock (bifascicular block)\r\n* Patients with myocardial infarction or unstable angina < 3 months prior to starting study drug\r\n* Congestive heart failure (CHF) New York (NY) Heart Association class III or IV
Impaired cardiac function including any one of the following:\r\n* Inability to monitor the QT interval on electrocardiogram (ECG)\r\n* Congenital long QT syndrome or a known family history of long QT syndrome\r\n* Clinically significant resting brachycardia (< 50 beats per minute)\r\n* Corrected QT (QTc) > 450 msec on baseline ECG; if QTc > 450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc\r\n* Myocardial infarction =< 12 months prior to starting study\r\n* Other clinically significant uncontrolled heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension)\r\n* History of or presence of clinically significant ventricular, atrial tachyarrhythmias or ejection fraction cutoff\r\n* Left ventricle ejection fraction < 45%\r\n* History of, congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:\r\n* With permanent cardiac pacemaker\r\n* Resting bradycardia defined as < 50 beats per minute\r\n* Corrected QT using Fridericia's method (QTcF) > 480 msec on screening electrocardiogram (ECG)\r\n* Complete left bundle branch block, bifascicular block\r\n* Any clinically significant ST segment and/or T-wave abnormalities\r\n* Presence of unstable atrial fibrillation (ventricular response rate > 100 beats per minute [bpm]); patients with stable atrial fibrillation can be enrolled provided they do not meet other cardiac exclusion criteria\r\n* Symptomatic congestive heart failure (New York Heart Association [NYHA] class III-IV)
Impaired cardiac function including any of the following:\r\n* Congenital long QT syndrome or a known family history of long QT syndrome;\r\n* History or presence of clinically significant ventricular or atrial tachyarrhythmias\r\n* Clinically significant resting bradycardia (< 50 beats per minute) \r\n* Inability to monitor the QT interval by electrocardiogram (ECG)\r\n* Corrected QT interval (QTc) > 450 msec on baseline ECG; if QTc > 450 and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc\r\n* Myocardial infarction within 1 year of starting study drug\r\n* Other clinically significant heart disease (e.g., unstable angina, congestive heart failure, or uncontrolled hypertension)
Impaired cardiac function or clinically significant cardiac diseases, including any one of the following: history or presence of sustained ventricular tachyarrhythmia; any history of ventricular fibrillation or torsade de pointes; bradycardia defined as heart rate (HR) < 50 beats per minute (bpm); patients with pacemakers are eligible if heart rate (HR) >= 50 bpm; screening ECG with a corrected QT using Fridericia's formula (QTcF) > 450 msec, right bundle branch block + left anterior hemiblock (bifascicular block), patients with myocardial infarction or unstable angina =< 6 months prior to starting study drug, other clinically significant heart disease (e.g., congestive heart failure [CHF] New York Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
Impaired cardiac function or clinically significant heart disease, including any one of the following:\r\n* Angina pectoris within 3 months\r\n* Acute myocardial infarction within 3 months\r\n* QT interval corrected using Fridericia’s formula (QTcF) > 450 msec for males and > 470 msec for females on the screening electrocardiogram (ECG)\r\n* A past medical history of clinically significant ECG abnormalities or a family history of prolonged QT-interval syndrome\r\n* Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
Impaired cardiac function or clinically significant cardiac diseases, including any one of the following: * History or presence of sustained ventricular tachyarrhythmia. (Patients with a history of atrial arrhythmia are eligible) * Any history of ventricular fibrillation or torsade de pointes * Bradycardia defined as heart rate (HR)< 50 bpm. Patients with pacemakers are eligible if HR >/= 50 bpm. * Screening electrocardiogram (ECG) with a corrected QT interval (QTc) or QTcF > 450 msec * Right bundle branch block + left anterior hemiblock (bifascicular block) * Patients with myocardial infarction or unstable angina </= 6 months prior to starting study drug * Other clinically significant heart disease (e.g., Congestive Heart Failure (CHF) New York Heart Association (NYHA) class III or IV , uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:\r\n* Left ventricular ejection fraction (LVEF) < 50% as determined by Multiple Grated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* ST depression or elevation of >= 1.5 mm in 2 or more leads\r\n* Congenital long QT syndrome\r\n* History or presence of ventricular arrhythmias or atrial fibrillation\r\n* Clinically significant resting bradycardia (< 50 beats per minutes)\r\n* Corrected QT interval (QTc) > 480 msec on screening electrocardiogram (ECG)\r\n* Complete left bundle branch block\r\n* Right bundle branch block + left anterior hemiblock (bifascicular block)\r\n* Unstable angina pectoris =<6 months prior to starting study drug\r\n* Acute myocardial infarction =< 6 months prior to starting study drug\r\n* Other clinically significant heart disease such as congestive heart failure requiring treatment (New York Heart Association [NYHA] class III or IV)
Other clinically significant heart disease (i.e., Grade ?3 hypertension, history of labile hypertension, or poor compliance with an anti-hypertensive regimen)
New York Heart Association (NYHA) cardiac class 3-4 heart disease as well as impaired cardiac function defined as: left ventricular ejection fraction (LVEF) < 45% as determined by multigated acquisition scan (MUGA) scan or electrocardiogram; complete left bundle branch block; use of cardiac pacemaker; ST depression of > 1 mm in 2 or more leads and/or T wave inversions in 2 or more continuous leads; congenital long QT syndrome; history of, or presence of significant ventricular or atrial tachyarrhythmias; clinically significant resting bradycardia (< 50 beats per minute [bpm]); corrected QT (QTc) > 450 msec on screening electrocardiogram (ECG) (using the Fridericia QTc [QTcF] formula); right bundle branch block plus left anterior hemiblock, bifascicular block; myocardial infarction within 12 months prior to starting AMN107 (nilotinib); unstable angina diagnosed or treated within the past 12 months; other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
Impaired cardiac function or clinically significant cardiac diseases, history of arrhythmia (including ventricular fibrillation or torsade de pointes), bradycardia < 50 beats per minute (bpm), screening electrocardiogram (ECG) with prolonged corrected QT (QTc) or uncontrolled hypertension
Impaired cardiac function including any one of the following: a. inability to monitor the QT interval on electrocardiogram (ECG), b. congenital long QT syndrome or a known family history of long QT syndrome, c. clinically significant resting brachycardia (< 45 beats per minute), d. QTc > 480 msec on baseline ECG; if QTc > 450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc, e. impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following: history of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) < 6 months prior to screening, symptomatic chronic heart failure, history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality < 6 months prior to screening except atrial fibrillation and paroxysmal supraventricular tachycardia
Other clinically significant heart disease (e.g., CHF NY Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen).
Impaired cardiac function or significant heart disease, including any one of the following:\r\n* Angina pectoris within 3 months\r\n* Acute myocardial infarction within 3 months\r\n* Corrected QT (QTc) > 450 msec on the screening electrocardiogram (ECG)\r\n* A past medical history of clinically significant ECG abnormalities or a family history of prolonged QT-interval syndrome\r\n* Other clinically significant heart disease (e.g. heart failure, uncontrolled/labile hypertension, or history of poor compliance with an antihypertensive regimen)
Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:\r\n* History or presence of sustained ventricular tachyarrhythmia; (patients with a history of atrial arrhythmia are eligible but should be discussed with Novartis prior to enrollment)\r\n* Any history of ventricular fibrillation or torsade de pointes\r\n* Bradycardia defined as heart rate (HR) < 50 beats per minute (bpm); patients with pacemakers are eligible if resting HR >= 50 bpm\r\n* Screening electrocardiogram (ECG) with a corrected QT with Fridericia's formula (QTcF) > 480 msec\r\n* Right bundle branch block + left anterior hemiblock (bifascicular block)\r\n* Patients with myocardial infarction or unstable angina =< 6 months prior to starting study drug\r\n* Other clinically significant heart disease (e.g., congestive heart failure [CHF] New York [NY] Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
Impaired cardiac function or clinically significant heart disease, including any one of the following: congestive heart failure, angina pectoris within 3 months, acute myocardial infarction within 3 months, Fridericia corrected QT interval (QTcF) > 450 milliseconds (msec) for males and > 470 msec for females on the screening electrocardiogram (ECG), history of clinically significant ECG abnormalities, family history of prolonged QT-interval syndrome, or other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:\r\n* History or presence of sustained ventricular tachyarrhythmia; (patients with a history of atrial arrhythmia are eligible but should be discussed with Novartis prior to enrollment)\r\n* Any history of ventricular fibrillation or torsade de pointes\r\n* Bradycardia defined as heart rate (HR) < 50 beats per minute (bpm); patients with pacemakers are eligible if HR >= 50 bpm\r\n* Screening electrocardiogram (ECG) with a QTc > 450 msec\r\n* Right bundle branch block + left anterior hemiblock (bifascicular block)\r\n* Patients with myocardial infarction or unstable angina =< 6 months prior to starting study drug\r\n* Other clinically significant heart disease (e.g., congestive heart failure [CHF] New York [NY] Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
Any of the following concurrent severe and/or uncontrolled medical conditions that could compromise participation in the study: \r\n* ST depression or elevation of >= 1.5 mm in 2 or more leads\r\n* Congenital long QT syndrome\r\n* History or presence of sustained ventricular arrhythmias or atrial fibrillation\r\n* Clinically significant resting bradycardia (< 50 beats per minutes)\r\n* Corrected QT interval (QTc) > 480 msec on screening electrocardiogram (ECG)\r\n* Complete left bundle branch block\r\n* Right bundle branch block + left anterior hemiblock (bifascicular block)\r\n* Unstable angina pectoris =< 6 months prior to starting study drug\r\n* Acute myocardial infarction =< 6 months prior to starting study drug\r\n* Other clinically significant heart disease such as congestive heart failure requiring treatment (New York Heart Association [NYHA] class III or IV) or uncontrolled hypertension (please refer to World Health Organization [WHO]-International Society of Hypertension [ISH] guidelines)
Impaired cardiac function or clinically significant cardiac diseases, including any one of the following: history or presence of sustained ventricular tachyarrhythmia; any history of ventricular fibrillation or torsade de pointes; bradycardia defined as heart rate (HR) < 50 beats per minute (bpm); patients with pacemakers are eligible if HR >= 50 bpm; screening electrocardiogram (ECG) with a corrected QT interval (QTc) > 450 msec; right bundle branch block + left anterior hemiblock (bifascicular block); patients with myocardial infarction or unstable angina =< 6 months prior to starting study drug; other clinically significant heart disease (e.g., congestive heart failure [CHF] New York [NY] Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
Impaired cardiac function or clinically significant heart disease, including any one of the following:\r\n* Angina pectoris within 3 months\r\n* Acute myocardial infarction within 3 months\r\n* Corrected QT (QTc) > 450 msec for males and > 470 msec for females on the screening electrocardiogram (ECG)\r\n* A past medical history of clinically significant ECG abnormalities or a family history of prolonged QT-interval syndrome\r\n* Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor adherence with an antihypertensive regimen)
Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:\r\n* Any history of ventricular fibrillation or torsade de pointes\r\n* Bradycardia defined as heart rate (HR) < 45 beats per minute (bpm); patients with pacemakers are eligible if HR >= 45 bpm\r\n* Screening electrocardiogram with a QT corrected for Fridericia's formula (QTcF) >= 480 msec\r\n* Right bundle branch block + left anterior hemiblock (bifascicular block)\r\n* Patients with myocardial infarction or unstable angina =< 12 months prior to starting study drug\r\n* Other clinically significant heart disease (e.g., Classification of Heart failure [CHF] New York Heart Association class III or IV, uncontrolled hypertension) as per discretion of principal investigator and/or treating physician\r\n* Patients using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug with the exception of drugs that are required for hematopoietic cell transplantation (HCT) patients
Cardiac criteria such as unstable angina, myocardial infarction within 6 months of screening, NY Heart Association Class 1 or 2 heart failure, QTc greater than 470 msec, congenital long Qt syndrome, symptomatic orthostatic hypotension within 6 months of screening, uncontrolled hypertension, or clinically important abnormalities in heart rhythm, conduction, morphology of resting ECG
Patients with cardiomyopathy and/or LVEF < LLN.
Prior or current cardiomyopathy including but not limited to the following: known hypertrophic cardiomyopathy, known arrhythmogenic right ventricular cardiomyopathy, previous moderate or severe impairment of left ventricular systolic function (left ventricular ejection fraction [LVEF] < 45% on echocardiography or equivalent on multigated acquisition scan [MuGA]) even if full recovery has occurred
Documented cardiomyopathy;
Active cardiomyopathy
Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes
Has significant cardiovascular disease with New York Heart Association (NYHA) class III or IV symptoms, or hypertrophic cardiomyopathy, or restrictive cardiomyopathy, or myocardial infarction within 3 months prior to enrollment, or unstable angina, or unstable arrhythmia as determined by history and physical examination
Patients with clinically significant cardiomyopathy requiring treatment
Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes
Patients with LVEF =< 40% from treatment with anthracyclines for all malignancies at any dose without evidence of other causes of cardiomyopathy
History of familial cardiomyopathy
History of infiltrative cardiomyopathy or restrictive cardiomyopathy
Transthyretin amyloid (ATTR) cardiomyopathy (CM)
Cardiomyopathy primarily caused by non-amyloid diseases (e.g. ischemic heart disease; valvular heart disease)
Symptomatic cardiomyopathy
Patients with LVEF =< 40% documented from treatment with anthracyclines for any malignancy at any dose at any time without evidence of other causes of cardiomyopathy
History of familial cardiomyopathy
History of infiltrative cardiomyopathy or restrictive cardiomyopathy
Documented cardiomyopathy
Documented cardiomyopathy
Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes
Known history of cardiomyopathy
Patients with clinically significant cardiomyopathy requiring treatment
Documented cardiomyopathy
Significant cardiovascular disease with New York Heart Association (NYHA) class III or IV symptoms, ejection fraction (EF) =< 40% or hypertrophic cardiomyopathy, or restrictive cardiomyopathy, or myocardial infarction within 6 months prior to enrollment, or unstable angina, or unstable arrhythmia as determined by history and physical examination. Echocardiogram will be performed during screening evaluation
Has significant cardiovascular disease with New York Heart Association (NYHA) class III or IV symptoms, ejection fraction (EF) =< 40% or hypertrophic cardiomyopathy, or restrictive cardiomyopathy, or myocardial infarction within 6 months prior to enrollment, or unstable angina, or unstable arrhythmia as determined by history and physical examination; echocardiogram will be performed during screening evaluation
Has significant cardiovascular disease with New York Heart Association (NYHA) class III or IV symptoms, ejection fraction (EF) =< 40% or hypertrophic cardiomyopathy, or restrictive cardiomyopathy, or myocardial infarction within 6 months prior to enrollment, or unstable angina, or unstable arrhythmia as determined by history and physical examination; echocardiogram will be performed during screening evaluation
Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes
Prior history of cardiomyopathy.
Uncontrolled hypertension or cardiomyopathy
Uncorrected primary obstructive or severe regurgitative valvular disease, nondilated (restrictive) or hypertrophic cardiomyopathy, or significant systemic ventricular outflow obstruction
Any grade immune-related pneumonitis, cardiomyopathy, or hepatitis
Have cardiomyopathy
Receiving treatment for cardiomyopathy or heart failure
Uncorrected primary obstructive or severe regurgitative valvular disease:\r\n* Nondilated (restrictive); or\r\n* Hypertrophic cardiomyopathy; or\r\n* Significant systemic ventricular outflow obstruction
Patients with any of the following cardiac conditions:\r\n* Symptomatic restrictive cardiomyopathy\r\n* Dilated 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
History of myocardial disease, such as myocarditis, cardiomyopathy, congestive heart failure, ischemic cardiomyopathy
Pre-existing ischemic heart disease (includes angina if documented in electronic medical record [EMR]) or ongoing cardiomyopathy.
Cirrhosis, cardiomyopathy, restrictive heart disease, or bronzing of the skin
Patient has clinically significant, uncontrolled heart disease and/or recent events including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 12 months prior to treatment start\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Patient has a left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening\r\n* History of any cardiac arrhythmias, eg., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months prior to treatment start\r\n* Family history of corrected QT interval (QTc) prolongation or of unexplainable sudden death at < 50 years of age\r\n* On screening 12 lead electrocardiogram (ECG), any of the following cardiac parameters: bradycardia (heart rate < 50 at rest), tachycardia (heart rate > 90 at rest), PR interval > 220 msec, QRS interval > 109 msec, or Fridericia corrected QT (QTcF) > 450 msec; congenital long QT syndrome or family history of long QT syndrome\r\n* Systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg\r\n* Bradycardia (heart rate < 50 at rest), by ECG or pulse, at screening
Clinically significant active cardiac disease, uncontrolled heart disease and/or a history of cardiac dysfunction including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 12 months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Patient has a left ventricular ejection fraction (LVEF) < 50% as determined by echocardiogram (ECHO) \r\n* History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening\r\n* Long QT syndrome or known family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: \r\n** Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia\r\n** Concomitant use of medication(s) with a known risk to prolong the QT interval and/or days prior to starting study drug) or replaced by safe alternative medication\r\n* 12-lead electrocardiogram (ECG), any of the following cardiac parameters:\r\n** QTc > 480 msec\r\n* Hypertension defined as: \r\n** Patients 1-12 years of age with blood pressure that is > 95th percentile for age, height and gender at the time of enrollment \r\n*** The normal blood pressure by height, age and gender tables can be accessed in the Generic Forms section of the PBTC members’ webpage\r\n** Patients who are >= 13 years of age with blood pressure > 130/80 mm of Hg at the time of enrollment\r\n* Note: if a blood pressure (BP) reading prior to enrollment does not meet parameters, blood pressure should be rechecked and documented to be within eligibility range prior to patient enrollment
Participants with uncontrolled intercurrent illness including, but not limited to:\r\n* Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities, including any of the following:\r\n** History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to screening\r\n** History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n** Documented cardiomyopathy\r\n** Left ventricular ejection fraction (LVEF) =< 50% as determined by multiple-gated acquisition (MUGA) scan or echocardiogram (ECHO) within six months prior to beginning protocol therapy\r\n** Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block)\r\n** Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:\r\n*** Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia\r\n*** Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued (within 5 half-lives or 7 days prior to starting study drug) or replaced by safe alternative medication\r\n** Systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg at screening\r\n** Impairment of gastrointestinal function or who have gastrointestinal disease that may significantly alter the absorption of study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea or malabsorption syndrome)\r\n** Patient with liver disease and Child-Pugh score B or C
Clinically significant, uncontrolled heart disease and/ or cardiac repolarization abnormalities including any of the following:\r\n* History of unstable angina pectoris, symptomatic pericarditis, myocardial infarction, coronary artery bypass grafting or coronary angioplasty =< 12 months prior to registration\r\n* History of documented congestive heart failure (New York Heart Association functional classification III - IV)\r\n* Documented cardiomyopathy\r\n* Left ventricular ejection fraction (LVEF) < 50% as determined by echocardiogram (ECHO)\r\n* Clinically significant cardiac arrhythmias (e.g ventricular tachycardia) , left bundle branch block, high-grade atrioventricular (AV) block (e.g bifascucular block, Mobitz type II and third degree AV block)\r\n* Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:\r\n** Risk factors for torsades de pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia\r\n** Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause torsades de pointe that cannot be discontinued (within 5 half-lives or =< 7 days prior to registration) or replaced by safe alternative medication\r\n** Inability to determine the QT interval on screening (QTcF, using Fridericia’ s correction)
Participants who have clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g. bifascicular block, Mobitz type II) and third-degree AV block\r\n* Documented cardiomyopathy\r\n* Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening\r\n* Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following\r\n** Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia\r\n** Inability to determine the QT interval on screening (QTcF, using Fridericia’s correction)\r\n* Systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg at screening
AZD5363 plus olaparib\r\n* Patients with breast, ovarian and endometrial cancers that carry an AKT1 mutation are excluded from the study due to another ongoing study that enrolls these patients; patients with these tumor types but other mutations can be enrolled in the study\r\n* Patients with type I or type II diabetes mellitus; type II diabetes mellitus is allowed if well controlled by dietary measures alone with a glycated hemoglobin (HbgA1c) < 8%; patients found to have a fasting glucose >= 7 mmol/L (126 mg/dL) or HbgA1c > 8% (64 mmol/L) at screening should be assessed for appropriate management according to local policy, of which those in whom dietary measures alone provide good diabetic control (HbgA1c < 8%) will be eligible for inclusion\r\n* Patient must have no evidence of troponin elevation (any common toxicity criteria [CTC] grade)\r\n* Patient must not have > stage II New York Heart Association (NYHA) classification cardiac status; recent history (i.e., within 6 months) of coronary artery disease or arteriosclerotic cardiovascular disease (angina, myocardial infarction [MI])\r\n* Patient must not have resting left ventricular ejection fraction (LVEF) < 55% measured by multi-gated acquisition (MUGA)/echocardiogram (ECHO)\r\n* Patient must not have PR interval greater than 200 msec\r\n* Patient must not have clinically significant PR (PQ) interval prolongation\r\n* Patient must not have resting LVEF < 55% measured by echocardiogram, regional wall abnormality on ECHO, or any clinically significant structural abnormalities on echocardiogram such as left ventricular hypertrophy or diastolic dysfunction or valvular disease\r\n* Patient must not have QTcF > 480 msec or b) family history of long QT Syndrome or\r\nc) evidence of recent myocardial infarction e.g. within 6 months prior to start of study treatment) or risk of having a re-infarction, or d) history of torsade de pointes or e) QTcF < 350 msec (short QT syndrome)\r\n* Patient must not have intermittent second or third degree atrioventricular (AV) block (second degree AV block [Mobitz Type I and II]; third degree AV block [complete heart block]); incomplete, full or intermittent bundle branch block (QRS 110-120ms with normal QRS and T wave morphology is permitted if there is no evidence of left ventricular hypertrophy); Mobitz type 1, Wenckebach while asleep is permitted\r\n* Patient must not have clinically significant abnormalities in T wave or ST-T changes that can be indicative or be suggestive of acute ischemic changes or acute injury pattern\r\n* Use of any known potent negative inotropic drug - calcium channel blockers: verapamil, diltiazem; beta-blockers (pending discussion with cardiac SKG): metoprolol, propranolol, atenolol, bisoprolol, carvedilol, timolol, sotalol, esmolol; anti- arrhythmics (class I): disopyramide, procainamide, mexiletine; (class III): amiodarone\r\n* Patients with uncontrolled hypotension (systolic blood pressure < 90 mmHg and/or diastolic blood pressure < 50 mmHg)\r\n* Patients with potassium or sodium levels outside the normal range for the site\r\n* Patients with proteinuria (3+ on dipstick analysis or > 500 mg/24 hours)
Clinically significant, uncontrolled heart disease and/or recent events including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 12 months prior to screening;\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV);\r\n* Documented cardiomyopathy;\r\n* Patient has a left ventricular ejection fraction < 50% as determined by multi-gated acquisition (MUGA) scan or echocardiography\r\n(ECHO) at screening;\r\n* History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrthymias, or conduction abnormality within 12 months of screening;\r\n* Bradycardia (heart rate < 50 at rest), by electrocardiography (ECG) or pulse, at screening;\r\n* Congenital long QT syndrome or family history of long QT syndrome;\r\n* Systolic blood pressure (SBP) > 160 or < 90 mm Hg
Clinically significant, uncontrolled heart disease and/or recent events including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty or stenting) or symptomatic pericarditis within 12 months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Patient has a left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) obtained during screening\r\n* History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening; patients with rate-controlled atrial fibrillation or flutter are permitted\r\n* Bradycardia (heart rate < 50 bpm at rest), by electrocardiography (ECG) or pulse, at screening\r\n* Congenital long QT syndrome or family history of long QT syndrome\r\n* Any of the following abnormalities on screening 12-lead ECG:\r\n** QTcF (Fridericia’s formula) > 450 msec\r\n** Bradycardia (heart rate < 50 bpm at rest)\r\n** PR interval > 220 msec\r\n** QRS interval > 109 msec\r\n* Documented cardiomyopathy\r\n* Systolic blood pressure > 160 mmHg or < 90 mmHg at screening
Impaired cardiac function or clinically significant cardiac disease including any of the following:\r\n* Congenital long QT syndrome\r\n* Screening electrocardiogram (ECG) with corrected QT (QTc) interval >= 500 milliseconds\r\n* Myocardial infarction (MI) or unstable angina =< 6 months of course 1, day 1 (C1D1); however, subjects with a history of MI between 6 and 12 months who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event would be eligible\r\n* Symptomatic coronary artery disease (CAD), e.g., angina Canadian class II-IV; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present\r\n* An ECG recorded at screening showing evidence of cardiac ischemia (ST depression of >= 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present\r\n* Other significant ECG abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (defined here as ventricular rate < 50 beats per minute [bpm]); right bundle-branch block + left anterior hemi-block (bifascicular block)\r\n* Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II to IV definitions and/or ejection fraction < 40% by multi gated acquisition scan (MUGA) scan or < 50% by echocardiogram and/or magnetic resonance imaging (MRI) history or presence of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), torsade de pointes, or cardiac arrest\r\n* Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes\r\n* Uncontrolled hypertension, i.e., blood pressure (BP) of >= 160/95; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria\r\n* Any cardiac arrhythmia requiring an anti-arrhythmic medication, excluding stable (i.e., at least 30 days from screening) doses of beta-blockers
Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including any of the following:\r\n* History of angina pectoris, symptomatic pericarditis, coronary artery bypass graft (CABG) or myocardial infarction within 6 months prior to study entry\r\n* Documented cardiomyopathy\r\n* Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening
History of cardiac failure, significant/symptomatic bradycardia, long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome or any of the following:\r\n* Known risk to prolong the QT interval or induce torsade’s de pointes\r\n* Uncorrected hypomagnesemia or hypokalemia\r\n* Systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg\r\n* Bradycardia (heart rate < 50 at rest), by electrocardiogram (ECG) or pulse\r\n* On screening, inability to determine the QTcF interval on the ECG (i.e.: unreadable or not interpretable) or QTcF > 450 (based on a mean of 3 ECGs)
Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality,\r\nincluding any of the following:\r\n* History of myocardial infarction (MI), angina pectoris, symptomatic pericarditis, or coronary artery bypass graft (CABG) within 6 months prior to study entry\r\n* Documented cardiomyopathy\r\n* Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:\r\n** Risk factors for torsades de pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia\r\n** Concomitant medication(s) with a known risk to prolong the QT interval and/or known to cause torsades de pointe that cannot be discontinued or replaced by safe alternative medication (e.g. within 5 half-lives or 7 days prior to starting study drug)\r\n** Inability to determine the QTcF interval\r\n* Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third degree AV block
Uncontrolled or significant cardiovascular disease, including any of the following:\r\n* Corrected QT (QTc) interval > 480 msec (mean value and manually verified) at 3 or more time points within a 24 hour period if necessary\r\n* Diagnosed or expected congenital long QT syndrome\r\n* Concurrent congestive heart failure, prior history of class III/IV cardiac disease (New York Heart Association)\r\n* Left ventricular ejection fraction < 50%\r\n* Prior history of cardiac ischemia or cardiac arrhythmia within the last 6 months; coronary angioplasty or stenting in the previous 12 months\r\n* Any history of second or third degree heart block (may be eligible if the subject currently has a pacemaker)\r\n* Uncontrolled hypertension defined as inability to maintain blood pressure below the limit of 140/90 mmHg\r\n* Known pulmonary hypertension
Clinically significant cardiac disease or impaired cardiac function, such as:\r\n* Congestive heart failure (CHF) requiring treatment (New York Heart Association [NYHA] grade >= 2) or left ventricular ejection fraction (LVEF) < 50% as determined by multi-gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening\r\n* History or current evidence of clinically significant cardiac arrhythmias, atrial fibrillation and/or conduction abnormality, e.g. congenital long QT syndrome, high-grade/complete atrioventricular (AV)-blockage\r\n* Acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft [CABG], coronary angioplasty, or stenting), < 3 months prior to screening\r\n* QT interval adjusted according to Fredericia (QTcF) > 480 msec on screening electrocardiogram (ECG)
Any known cardiac abnormalities such as:\r\n* Congenital long QT syndrome\r\n* Corrected QT (QTc) interval >= 500 milliseconds\r\n* Patients taking drugs leading to significant QT prolongation\r\n* Myocardial infarction within 6 months of cycle1 day 1 (C1D1); (subjects with a history of myocardial infarction between 6 and 12 months prior to C1D1 who are asymptomatic and have had a negative cardiac risk assessment [treadmill stress test, nuclear medicine stress test, or stress echocardiogram] since the event, may participate)\r\n* Other significant electrocardiogram (ECG) abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min)\r\n* Symptomatic coronary artery disease (CAD), e.g., angina Canadian class II-IV; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present\r\n* An ECG recorded at screening showing evidence of cardiac ischemia (ST depression of >= 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present\r\n* Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II to IV definitions and/or ejection fraction < 40% by multi gated acquisition (MUGA) scan or < 50% by echocardiogram and/or magnetic resonance imaging (MRI)\r\n* A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest \r\n* Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes\r\n* Uncontrolled hypertension, i.e., blood pressure (BP) of >= 160/95; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria or\r\n* Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)
Clinically significant uncontrolled heart disease and/or recent cardiac event within 6 months prior to enrollment, such as:\r\n* History of angina pectoris, symptomatic pericarditis, or myocardial infarction\r\n* Left ventricular ejection fraction (LVEF) < 45% as determined by echocardiogram (ECHO) or multi gated acquisition (MUGA) scan\r\n* History or presence of any cardiac arrhythmias, e.g. ventricular, supraventricular, nodal arrhythmias or conduction abnormality; stable atrial fibrillation within 6 months prior to randomization is permitted\r\n* Presence of unstable atrial fibrillation (ventricular response rate > 100 beats per minute [bpm]); NOTE: patients with stable atrial fibrillation\r\n* Resting heart rate < 50 bpm\r\n* Complete left bundle branch block (LBBB), bifascicular block\r\n* Congenital long QT syndrome\r\n* Any clinically significant ST segment and/or T-wave abnormalities\r\n* Corrected QT (QTcF) > 450 msec for males and females using Fridericia’s correction on screening electrocardiogram (ECG) by mean value of triplicate ECGs\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Uncontrolled hypertension defined by a systolic blood pressure (SBP) >= 150 mmHg and/or diastolic blood pressure (DBP) >= 100 mmHg with or without antihypertensive medication; NOTE: initiation or adjustment of antihypertensive medication(s) is allowed prior to screening\r\n* Other clinically significant heart disease or vascular disease
Cardiac conditions as follows: uncontrolled hypertension (blood pressure [BP] >= 150/95 mmHg despite medical therapy); acute coronary syndrome within 6 months prior to starting treatment; uncontrolled angina - Canadian Cardiovascular Society grade II-IV despite medical therapy; symptomatic heart failure New York Heart Association (NYHA) class II-IV, prior or current cardiomyopathy, or severe valvular heart disease; prior or current cardiomyopathy including but not limited to the following: known hypertrophic cardiomyopathy or known arrhythmogenic right ventricular cardiomyopathy; previous moderate or severe impairment of left ventricular systolic function (left ventricular ejection fraction [LVEF] < 45% on echocardiography or equivalent on multigated acquisition [MUGA]) even if full recovery has occurred; severe valvular heart disease; baseline LVEF below the lower limit of normal (LLN) measured by echocardiogram (ECHO) or institution’s LLN for MUGA; atrial fibrillation with a ventricular rate > 100 bpm on electrocardiogram (ECG) at rest; corrected QT interval by Fridericia (QTcF) > 470 ms on two or more timepoints or other factors that increase the risk of QT prolongation such as family history of long QT syndrome
Any of the following cardiac abnormalities (only for patients receiving romidepsin):\r\n* Congenital long QT syndrome;\r\n* Corrected QT (QTc) interval ? 501 milliseconds;\r\n* Patients taking drugs leading to significant QT prolongation;\r\n* Myocardial infarction within 6 months of cycle 1, day 1; (Subjects with a history of myocardial infarction between 6 and 12 months prior to cycle 1, day 1, who are asymptomatic and have had a negative cardiac risk assessment [treadmill stress test, nuclear medicine stress test, or stress echocardiogram] since the event, may participate);\r\n* Other significant electrocardiogram (ECG) abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min);\r\n* Symptomatic coronary artery disease (CAD), e.g., angina Canadian class II-IV; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;\r\n* An ECG recorded at screening showing evidence of cardiac ischemia (ST depression of ? 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;\r\n* Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II to IV definitions and/or ejection fraction < 40% by multitargeted acquisition (MUGA) scan or < 50% by echocardiogram and/or magnetic resonance imaging (MRI);\r\n* A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), torsade de pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD);\r\n* Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes;\r\n* Uncontrolled hypertension, i.e., blood pressure (BP) of ? 160/95; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria; or\r\n* Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)
Patients with the following cardiac conditions are excluded:\r\n* Uncontrolled hypertension (adults: blood pressure [BP] of >= 150/95 despite medical support/management; participants 18 years of age and younger should have a blood pressure =< 95th percentile for age, height and gender; preexisting hypertension in adults should be controlled [either with pharmacological or non-pharmacological methods] at the time of enrollment)\r\n* Acute coronary syndrome within 6 months prior to starting treatment\r\n* Uncontrolled angina – Canadian Cardiovascular Society grade II-IV despite medical support/management\r\n* Heart failure New York Heart Association (NYHA) class II or above\r\n* Prior or current cardiomyopathy including but not limited to the following:\r\n** Known hypertrophic cardiomyopathy\r\n* Known arrhythmogenic right ventricular cardiomyopathy\r\n* Baseline left ventricular ejection fraction (LVEF) =< 55%\r\n* Previous moderate or severe impairment of left ventricular systolic function (LVEF < 50% on echocardiography or equivalent on Multi-Gated Acquisition Scan [MUGA]) even if full recovery has occurred\r\n* Severe valvular heart disease\r\n* Atrial fibrillation with a ventricular rate > 100 beats per minute (bpm) on electrocardiogram (ECG) at rest\r\n* QT interval corrected according to Fridericia’s formula (QTcF) interval > 450 msec or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) are excluded.; the use of medication(s) that can prolong QTc interval is prohibited while treated on this study
Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities, including any of the following:\r\n* New York Heart Association functional classification III-IV\r\n* Documented cardiomyopathy\r\n* Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening\r\n* Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block)\r\n* Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesaemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia; concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued (within 5 half-lives or 7 days prior to starting study drug) or replaced by safe alternative medication\r\n* Inability to determine the QT interval on screening (QTcFusing Fridericia’s correction)\r\n* Systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg at screening
Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality including any of the following:\r\n* History of myocardial infarction (MI), angina pectoris, symptomatic pericarditis, or coronary artery bypass graft (CABG) within 6 months prior to study entry\r\n* Documented cardiomyopathy\r\n* Patient has a known left ventricular fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* Long QT syndrome or family history of long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:\r\n** Risk factors for torsades de pointe (TdP) including uncorrected hypokalemia or hypomagnesaemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia\r\n** Concomitant medications(s) with a known risk to prolong the QT interval and/or known to cause torsades de pointe that cannot be discontinued or replaced by safe alternative medication (e.g. within 5 half-lives or 7 days prior to starting study drug)\r\n** Inability to determine the corrected QT (QTc) interval\r\n* Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third degree AV block)
Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities, including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening\r\n* Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block)\r\n* Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:\r\n* Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia\r\n* Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued (within 5 half-lives or 7 days prior to starting study drug) or replaced by safe alternative medication\r\n* Inability to determine the QT interval on screening (QTcF, using Fridericia’s correction)\r\n* Systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg at screening
Known cardiac disorder, including:\r\n* Uncontrolled hypertension (blood pressure [BP] of >= 150/95 despite medical support/management)\r\n* Acute coronary syndrome within 6 months prior to starting treatment\r\n* Uncontrolled angina – Canadian Cardiovascular Society grade II-IV despite medical support/management\r\n* Heart failure New York Heart Association (NYHA) class II or above\r\n* Prior or current cardiomyopathy including but not limited to the following:\r\n** Known hypertrophic cardiomyopathy\r\n* Known arrhythmogenic right ventricular cardiomyopathy\r\n* Baseline left ventricular ejection fraction (LVEF) =< 55%\r\n* Previous moderate or severe impairment of left ventricular systolic function (LVEF < 45% on echocardiography or equivalent on multi-gated acquisition scan [MUGA])\r\neven if full recovery has occurred\r\n* Severe valvular heart disease\r\n* Atrial fibrillation with a ventricular rate > 100 beats per minute (bpm) on electrocardiography (ECG) at rest\r\n* Fridericia's correction formula (QTcF) interval > 450 msec or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) are excluded; the use of medication(s) that can prolong corrected QT (QTc) interval is prohibited while treated on this study
Patient has active cardiac disease or a history of cardiac dysfunction including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 12 months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening\r\n* Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g. bifascicular block, Mobitz type II and third-degree AV block)\r\n* Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:\r\n** Risk factors for torsades de pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia\r\n** Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause torsades de pointe that cannot be discontinued (within 5 half-lives or 7 days prior to starting study drug) or replaced by safe alternative medication\r\n** Inability to determine the QT interval on screening (QTcF, using Fridericia’s correction)\r\n* Systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg at screening
Any known cardiac abnormalities such as: \r\n* Congenital long QT syndrome \r\n* Corrected QT (QTc) interval >= 485 milliseconds;\r\n* Myocardial infarction within 6 months of course 1 day 1 (C1D1); subjects with a history of myocardial infarction between 6 and 12 months prior to C1D1 who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event may participate;\r\n* Other significant electrocardiogram (ECG) abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min) trial treatments\r\n* Symptomatic coronary artery disease (CAD), e.g., angina; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;\r\n* An ECG recorded at screening showing evidence of cardiac ischemia (ST depression, depression of >= 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;\r\n* Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II to IV definitions and/or ejection fraction < 40% by multi gated acquisition (MUGA) scan or < 50% by echocardiogram and/or magnetic resonance imaging (MRI); \r\n* A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), torsade de pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD); \r\n* Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes; \r\n* Uncontrolled hypertension, i.e., blood pressure (BP) of >= 160/95; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria; or \r\n* Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)\r\n* Patients taking drugs leading to significant QT prolongation
The following cardiac abnormalities:\r\n* Congenital long QT syndrome\r\n* Corrected QT (QTc)/ Fridericia's correction QT (QTf) interval >= 480 milliseconds; unless secondary to pacemaker or bundle branch block\r\n* Myocardial infarction within 6 months (subjects with a history of myocardial infarction within the last 6 to 12 months who are asymptomatic and have had a negative cardiac risk assessment [treadmill stress test, nuclear medicine stress test, or stress echocardiogram] since the event may participate)\r\n* Other significant electrocardiogram (ECG) abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block\r\n* Symptomatic coronary artery disease (CAD), e.g. angina Canadian class II-IV; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present\r\n* An ECG recorded at screening showing evidence of cardiac ischemia (ST depression of >= 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the patient should have a stress imaging study and. if abnormal, angiography to define whether or not CAD is present\r\n* Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II to IV and/or ejection fraction < 45% by multigated acquisition (MUGA), echocardiogram, or cardiac magnetic resonance imaging (MRI)\r\n* A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), torsade de pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD)\r\n* Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes\r\n* Uncontrolled hypertension, i.e., blood pressure (BP) of >= 170/95; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month prior to study registration) and meet all other inclusion criteria\r\n* Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)\r\n* For patients enrolling on the romidepsin arm; taking drugs associated with significant QTc/QTf prolongation, unless able to be switched to non-QTc/QTf prolonging medication or on a stable dose without significant QT prolongation (> 470 msec)\r\n** Caution should be used when administering study drugs to patients taking medications significantly metabolized by these enzymes; particular attention should be paid to patients receiving warfarin; patients should have coagulation parameters monitored regularly, and warfarin dose adjusted accordingly; if these drugs cannot be discontinued or replaced, enrollment may be allowed after discussion with MSK principle investigator (PI)
Any known cardiac abnormalities such as:\r\n* Congenital long QT syndrome\r\n* Corrected QT (QTc) interval >= 500 milliseconds\r\n* Myocardial infarction within 6 months of transplantation; subjects with a history of myocardial infarction between 6 and 12 months prior to transplant who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event may participate\r\n* Other significant electrocardiogram (ECG) abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min)\r\n* Symptomatic coronary artery disease (CAD), e.g., angina Canadian class II-IV; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present\r\n* An ECG recorded at screening showing evidence of cardiac ischemia (ST depression of >= 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present\r\n* Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II to IV definitions and/or ejection fraction < 40% by multi gated acquisition (MUGA) scan or < 50% by echocardiogram and/or magnetic resonance imaging (MRI)\r\n* A known history or sustained ventricular tachycardia (VT), ventricular fibrillation (VF), torsade de pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD)\r\n* Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes\r\n* Uncontrolled hypertension, defined as blood pressure (BP) >= 160/95; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria\r\n* Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)\r\n* Patients taking drugs leading to significant QT prolongation within the specified wash out period\r\n* Concomitant use of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors
Patient has known clinically significant cardiac disease or impaired cardiac function, such as:\r\n* Congestive heart failure requiring treatment (New York Heart Association grade >= 2), left ventricular ejection fraction (LVEF) < 50% as determined by multigated acquisition (MUGA) scan or ECHO. \r\n* History or current evidence of clinically significant cardiac arrhythmias, atrial fibrillation, and/or conduction abnormality, e.g., congenital long QT syndrome, high-grade/complete arteriovenous blockage.\r\n* Acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft, coronary angioplasty, or stenting) < 3 months prior to screening.
Patient has clinically significant cardiac disease or impaired cardiac function, such as:\r\n* Congestive heart failure (CHF) requiring treatment (New York Heart Association [NYHA] Grade >= 2), left ventricular ejection fraction (LVEF) < 50% as determined by multi-gated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* History or current evidence of clinically significant cardiac arrhythmias, atrial fibrillation and/or conduction abnormality, e.g. congenital long QT syndrome, high-grade/complete atrioventricular (AV)-blockage; patients with asymptomatic and rate-controlled atrial fibrillation are not excluded\r\n* Acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft (CABG), coronary angioplasty, or stenting), < 3 months prior to screening
Significant cardiac disease or abnormality, including any one of the following:\r\n* Left ventricular ejection fraction < 50% at screening (assessed by echocardiography, cardiac MRI or multigated acquisition [MUGA])\r\n* Corrected QT Fridericia's correction formula (QTcF) > 470 ms on screening electrocardiogram (ECG), or a clinically-relevant ECG abnormality\r\n* Congenital long QT syndrome\r\n* History of sustained ventricular tachycardia, ventricular fibrillation, or torsades de pointes\r\n* Presence of atrial fibrillation with tachyarrhythmia (ventricular response rate > 100 beats per minute [bpm])\r\n* Bradycardia (heart rate < 50 bpm)\r\n* Complete left bundle branch block\r\n* Bifascicular block (complete right bundle branch block and anterior or posterior left hemiblock)\r\n* Myocardial infarction, acute coronary syndrome (including unstable angina), coronary revascularization procedures, or coronary arterial bypass grafting within the 6 months prior to starting study drug\r\n* Cardiac troponin (either troponin T or troponin I) > ULN\r\n* Congestive heart failure of New York Heart Association class III or IV\r\n* Unstable angina pectoris
Patients with the following cardiac conditions are excluded:\r\n* Uncontrolled hypertension (blood pressure [BP] of >= 150/95 despite medical support/management)\r\n* Acute coronary syndrome within 6 months prior to starting treatment\r\n* Uncontrolled angina – Canadian Cardiovascular Society grade II-IV despite medical support/management\r\n* Heart failure New York Heart Association (NYHA) class II or above\r\n* Prior or current cardiomyopathy (within 6 months) including but not limited to the following:\r\n** Known hypertrophic cardiomyopathy\r\n** Known arrhythmogenic right ventricular cardiomyopathy\r\n** Abnormal ejection fraction (echocardiogram [ECHO]) =< 53% (if a range is given then the upper value of the range will be used) or cardiac MRI\r\n** Previous moderate or severe impairment of left ventricular systolic function (left ventricular ejection fraction [LVEF] < 45% on echocardiography or equivalent on multi-gated acquisition scan [MUGA]) even if full recovery has occurred; echocardiogram (Echo) and additional cardiac studies not indicated unless clinically symptomatic or patient has significant cardiac history\r\n** Severe valvular heart disease\r\n** Atrial fibrillation with a ventricular rate > 100 beats per minute (bpm) on electrocardiogram (ECG) at rest\r\n** Fridericia's corrected QT interval (QTcF) >= 450 msec or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) are excluded; the use of medication(s) that can prolong QTc interval is prohibited while treated on this study
Patients has any of the following cardiac abnormalities:\r\n* Symptomatic congestive heart failure\r\n** History of documented congestive heart failure (New York Heart Association functional classification III-IV), documented cardiomyopathy\r\n** Left ventricular ejection fraction < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) \r\n* Myocardial infarction =< 6 months prior to enrollment \r\n* Unstable angina pectoris\r\n* Serious uncontrolled cardiac arrhythmia\r\n* Symptomatic pericarditis\r\n* Corrected QT interval using Fridericia's formula (QTcF) > 480 msec on the screening electrocardiogram (ECG) (using the QTcF formula)
Clinically significant, uncontrolled heart disease and/or a recent events including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 12 months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Patient has a Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening\r\n* History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, conduction abnormality in the previous 12 months of screening\r\n* Congenital long QT syndrome or family history of long QT syndrome\r\n* Sustained systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg at screening; must be corrected or controlled prior to starting study\r\n* Bradycardia (heart rate < 50 at rest) by electrocardiogram (ECG) or pulse, at screening\r\n* On screening inability to determine the QTcF interval on the ECG (i.e.: unreadable or not interpretable) or QTcF > 480 msec (using Fridericia’s correction); all as determined by screening ECG (mean of triplicate ECGs)
Clinically significant, uncontrolled heart disease and/ or a history of cardiac dysfunction including any of the following:\r\n* History of unstable angina pectoris, symptomatic pericarditis, myocardial infarction, coronary artery bypass grafting or coronary angioplasty within 12 months prior to study entry\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Patient has a left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* History of clinically significant ventricular arrhythmia and/or conduction delays within 12 months of screening\r\n* Systolic blood pressure > 160 mmHg or < 90 mmHg\r\n* Congenital long QT syndrome or family history of long QT syndrome\r\n* Bradycardia (heart rate < 50 at rest) by electrocardiogram (ECG) or pulse at screening.
Clinically significant cardiac disease or impaired cardiac function, such as:\r\n* Congestive heart failure (CHF) requiring treatment (New York Heart Association [NYHA] grade >= 2), left ventricular ejection fraction (LVEF) < 50% as determined by multi-gated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* History or current evidence of unstable, clinically significant cardiac arrhythmias or patients that require medications with a narrow therapeutic window, atrial fibrillation and/or conduction abnormality, e.g. congenital long QT syndrome, high-grade/complete atrioventricular (AV)-blockage\r\n* Acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft [CABG], coronary angioplasty, or stenting), < 3 months prior to screening
Clinically significant cardiac disease or impaired cardiac function, such as:\r\n* Baseline left ventricular ejection fraction (LVEF) < 50% on baseline echocardiogram or multi gated acquisition scan (MUGA)\r\n* Congestive heart failure requiring treatment (e.g., New York Heart Association class II, III or IV) within 6 months prior to screening\r\n* Acute coronary syndromes < 3 months prior to screening (including myocardial infarction, unstable angina, coronary artery bypass graft, coronary angioplasty, or stenting)\r\n* Uncontrolled arterial hypertension defined by blood pressure > 140/100 mm Hg at rest (average of 3 consecutive readings)\r\n* History or current evidence of unstable, clinically significant cardiac arrhythmias\r\n* Patients that require medications with a narrow therapeutic window\r\n* Clinically significant conduction abnormality, e.g. congenital long QT syndrome, high-grade/complete atrioventricular (AV)-blockage\r\n* Corrected QT interval (QTc) > 480 msec on screening electrocardiogram (ECG)
Subject has active cardiac disease or a history of cardiac dysfunction including any of the following:\r\n* Congenital long QT syndrome\r\n* Corrected QT (QTc) interval >= 500 ms on the screening electrocardiogram (ECG) (using the corrected QT Fridericia [QTcF] formula)\r\n* Myocardial infarction within 6 months of course 1 day 1 (C1D1); subjects with a history of myocardial infarction between 6 and 12 months prior to C1D1 who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event may participate\r\n* Other significant ECG abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min)\r\n* Symptomatic coronary artery disease (CAD), e.g., angina Canadian class II-IV; in any subject in whom there is doubt, the subject should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present\r\n* An ECG recorded at screening showing evidence of cardiac ischemia (ST depression of >= 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the subject should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present\r\n* Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II to IV definitions and/or ejection fraction < 40% by multi gated acquisition (MUGA) scan or < 50% by echocardiogram and/or magnetic resonance imaging (MRI)\r\n* A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), torsade de pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD)\r\n* Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes\r\n* Uncontrolled hypertension, i.e., blood pressure (BP) of >= 160/95; subjects who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria\r\n* Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)\r\n* Subjects taking drugs leading to significant QT prolongation\r\n* Concomitant use of cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors
Clinically significant, uncontrolled heart disease or cardiac repolarization abnormalities and/or recent events including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening\r\n* Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g. bifascicular block, Mobitz type II and third-degree AV block) long QT syndrome or family history of long QT syndrome\r\n* Idiopathic sudden death or congenital long QT syndrome\r\n* Risk factors for torsades de pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia\r\n* Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause torsades de pointe that cannot be discontinued (within 5 half-lives or 7 days prior to starting study drug) or replaced by safe alternative medication\r\n* Inability to determine the QT interval on screening (corrected QT interval [QTcF], using Fridericia’s correction)\r\n* Systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg at screening\r\n* Bradycardia (heart rate < 50 at rest), by electrocardiogram (ECG) or pulse, at screening\r\n* Tachycardia (heart rate > 110 at rest), by ECG or pulse at screening
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, known serious cardiac illness or psychiatric illness/social situations that would limit compliance with study requirements; known serious cardiac illness or medical conditions include, but are not limited to:\r\n* History of documented congestive heart failure (CHF), New York Heart Association (NYHA) class II/III/IV, with a history of dyspnea, orthopnea, or edema that requires current treatment with angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, beta blockers, or diuretics\r\n** NOTE: use of these medications for the treatment of hypertension is allowed\r\n* Screening QTc (QT interval corrected for heart rate) > 470 msec or history of QT (cardiac interval from start of Q wave to end of T wave) prolongation while taking other medications\r\n* High-risk uncontrolled arrhythmias (ventricular arrhythmias, high-grade atrioventricular [AV]-block, supra-ventricular arrhythmias that are not adequately rate-controlled)\r\n* Arrhythmias that require current treatment with the following anti-arrhythmic drugs: flecainide, moricizine, or propafenone\r\n* Current coronary artery disease with a history of myocardial infarction, angioplasty, or coronary bypass surgery within the preceding 6 months, or angina pectoris that has been symptomatic within the preceding 6 months
Patient has impaired cardiac function including any of the following: \r\n* Presence or history of pericardial effusion and/or pericarditis\r\n* Acute myocardial infarction, symptomatic angina pectoris =< 6 months prior to starting study drug \r\n* Presence of congestive heart failure >= New York Heart Association (NYHA) class 3\r\n* Corrected QT interval (QTc) > 480 ms on a screening electrocardiogram (ECG) \r\n* Screening left ventricular ejection fraction (LVEF) < 45% by echocardiography or multi gated acquisition scan (MUGA) \r\n* Uncontrolled cardiac arrhythmia including uncontrolled atrial fibrillation/atrial flutter/sinus tachycardia, complete left bundle branch block, congenital long QT syndrome\r\n* Presence of permanent cardiac pacemaker \r\n* Other clinically significant heart disease
Clinically significant, uncontrolled heart disease and/or recent events including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 12 months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Patient has a left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening\r\n* History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening\r\n* Congenital long QT syndrome or family history of long QT syndrome\r\n* Bradycardia (heart rate <50 at rest), by electrocardiography (ECG) or pulse, at screening\r\n* Systolic blood pressure (SBP) >160 mmHg or <90 mmHg at screening
Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities, including any of the following: a. History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to screening. b. History of documented congestive heart failure (New York Heart Association functional classification III-IV). c. Documented cardiomyopathy. d. Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening. e. Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block). Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: a. Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia. b. Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued (within 5 half-lives or 7 days prior to starting study drug) or replaced by safe alternative medication. c. Inability to determine the QT interval on screening (QTcF, using Fridericia’s correction). d. Systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg at screening.
Impaired cardiac function or clinically significant cardiac diseases, including any of the following: a) history of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis less than 12 months prior to screening b) history of documented congestive heart failure (New York Heart Association functional classification III-IV) c) documented cardiomyopathy d) patient has a left ventricular ejection fraction (LVEF) less than 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening e) history of ventricular, supraventricular, nodal arrhythmias, or any other cardiac arrhythmias, long QT syndrome or conduction abnormality within 12 months prior to starting study drug f) congenital long QT syndrome or a family history of corrected QT interval (QTc) prolongation g) on screening, inability to determine the corrected QT for Fridericia (QTcF) interval on the electrocardiogram (ECG) (i.e.: unreadable or not interpretable) or QTcF > 450 msec (using Fridericia’s correction); all as determined by screening ECG (mean of triplicate ECGs)
Clinically significant cardiac disease or impaired cardiac function such as: \r\n* Congestive heart failure (CHF) requiring treatment (New York Heart Association >= grade 2), left ventricular ejection fraction (LVEF) =< 50% dose determined by multi-gated acquisition (MUGA) scan or echocardiogram, or uncontrolled arterial hypertension defined by blood pressure greater than 140/80 mmHg at rest (average of 3 consecutive readings) \r\n* History or current evidence of clinically significant cardiac arrhythmias, atrial fibrillation and/or conduction abnormality, (e.g. congenital long QT syndrome, high grade/complete atrioventricular [AV] blockage)\r\n* Acute coronary syndrome (including myocardial infarction, unstable angina, coronary artery bypass graft [CABG], for coronary angiography angioplasty and stenting), < 3 months prior to screening\r\n* QT interval adjusted according to Fridericia (QTcF) > 480 msec on screening electrocardiogram (EKG)
Patients with clinically significant cardiac disease or impaired cardiac function are not eligible for participation; this includes patients with:\r\n* Congestive heart failure (CHF) requiring treatment (New York Heart Association [NYHA] grade >= 2)\r\n* Left ventricular ejection fraction (LVEF) < 50% as determined by multi-gated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* Uncontrolled arterial hypertension defined by blood pressure > 140/100 mm Hg at rest (average of 3 consecutive readings)\r\n* History or current evidence of unstable, clinically significant cardiac arrhythmias or patients that require medications with a narrow therapeutic window, atrial fibrillation and/or conduction abnormality (e.g. congenital long QT syndrome, high-grade/complete atrioventricular [AV]-blockage)\r\n* Acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft [CABG], coronary angioplasty, or stenting), < 3 months prior to screening\r\n* QTc > 460 msec on screening
Any known cardiac abnormalities such as:\r\n* Congenital long QT syndrome\r\n* Corrected QT (QTc) interval >= 500 milliseconds\r\n* Patients taking drugs leading to significant QT prolongation \r\n* Myocardial infarction within 6 months of course 1 day 1 (C1D1); (subjects with a history of myocardial infarction between 6 and 12 months prior to C1D1 who are asymptomatic and have had a negative cardiac risk assessment [treadmill stress test, nuclear medicine stress test, or stress echocardiogram] since the event, may participate)\r\n* Other significant electrocardiogram (ECG) abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min)\r\n* Symptomatic coronary artery disease (CAD), e.g., angina Canadian class II-IV; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present\r\n* An ECG recorded at screening showing evidence of cardiac ischemia (ST depression of >= 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present\r\n* Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II to IV definitions and/or ejection fraction < 40% by multigated acquisition (MUGA) scan or < 50% by echocardiogram and/or MRI;\r\n* A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD)\r\n* Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes\r\n* Uncontrolled hypertension, i.e., blood pressure (BP) of >= 160/95; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria; or\r\n* Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)
Clinically significant cardiac disease or impaired cardiac function, such as:\r\n* Congestive heart failure requiring treatment (e.g., New York Heart Association class II, III or IV)\r\n* Acute coronary syndromes < 3 months prior to screening (including myocardial infarction, unstable angina, coronary artery bypass graft, coronary angioplasty, or stenting)\r\n* Uncontrolled arterial hypertension defined by blood pressure > 140/100 mm Hg at rest (average of 3 consecutive readings)\r\n* History or current evidence of unstable, clinically significant cardiac arrhythmias or patients that require medications with a narrow therapeutic window, atrial fibrillation and/or conduction abnormality, e.g. congenital long QT syndrome, high-grade/complete atrioventricular (AV) blockage\r\n* Corrected QT interval (QTc) > 480 msec on screening electrocardiogram (ECG)
Participants with any of the following cardiac conditions:\r\n* History of long QT syndrome\r\n* Frederica corrected QT interval (QTcF) >= 450 ms during screening electrocardiogram (ECG)\r\n* History of clinically manifest ischemic heart disease including myocardial infarction, stable or unstable angina pectoris, coronary arteriography or cardiac stress testing/imaging with findings consistent with infarction or clinically significant coronary occlusion =< 6 months prior to study start\r\n* History of heart failure or left ventricular (LV) dysfunction (left ventricular ejection fraction [LVEF] =< 45%) by multi gated acquisition scan (MUGA) or echocardiogram (ECHO)\r\n* Clinically significant ECG abnormalities including one or more of the following: left bundle branch block (LBBB), right bundle branch block (RBBB) with left anterior hemiblock (LAHB); ST segment elevations or depressions > 1 mm, or 2nd (Mobitz II) or 3rd degree atrioventricular (AV) block\r\n* History and presence of atrial fibrillation, atrial flutter or ventricular arrhythmias including ventricular tachycardia or torsades de pointes\r\n* Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with a hypertensive regimen)\r\n* Clinically significant resting bradycardia (< 50 beats per minute)\r\n* Patients who are currently receiving treatment with any medication which has a relative risk or prolonging the corrected QT (QTc) interval or inducing torsades de pointes and cannot be switched or discontinued to an alternative drug prior to commencing AUY922 dosing\r\n* Patients who are on a cardiac pacemaker
Participants with following cardiac criteria:\r\n* History of long QT syndrome\r\n* Fridericia corrected QT interval (QTcF) >= 450 ms during screening electrocardiogram (ECG)\r\n* History of clinically manifest ischemic heart disease including myocardial infarction, stable or unstable angina pectoris, coronary arteriography or cardiac stress testing/imaging with findings consistent with infarction or clinically significant coronary occlusion =< 6 months prior to study start\r\n* History of heart failure or left ventricular (LV) dysfunction (LV ejection fraction [EF] =< 45%) by multi gated acquisition scan (MUGA) or echocardiogram (ECHO)\r\n* Clinically significant ECG abnormalities including one or more of the following: left bundle branch block (LBBB), right bundle branch block (RBBB) with left anterior hemiblock (LAHB); ST segment elevations or depressions > 1mm, or 2nd (Mobitz II) or 3rd degree atrioventricular block (AV) block\r\n* History and presence of atrial fibrillation, atrial flutter or ventricular arrhythmias including ventricular tachycardia or torsades de pointes\r\n* Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with a hypertensive regimen)\r\n* Clinically significant resting bradycardia (< 50 beats per minute)\r\n* Participants who are currently receiving treatment with any medication which has a relative risk or prolonging the QTcF interval or inducing torsades de pointes (as listed in protocol) and cannot be switched or discontinued to an alternative drug prior to commencing AUY922 dosing\r\n* Participants who are on a cardiac pacemaker
The following cardiac abnormalities:\r\n* Congenital long QT syndrome\r\n* Corrected QT (QTc) interval >= 480 milliseconds\r\n** A QTc interval between 480-499 milliseconds (msec) in the presence of a bundle branch block (BBB) or pacemaker is eligible in phase IIa after discussion with MSK principal investigator\r\n* Myocardial infarction within 6 months of cycle one, day one (C1D1); subjects with a history of myocardial infarction between 6 and 12 months prior to C1D1 who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event may participate\r\n* Other significant electrocardiogram (ECG) abnormalities including second (2nd) degree atrio-ventricular (AV) block type II, third (3rd) degree AV block\r\n* Symptomatic coronary artery disease (CAD), e.g., angina Canadian class II-IV; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present\r\n* An ECG recorded at screening showing evidence of cardiac ischemia (ST depression of >= 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present\r\n* Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II to IV definitions and/or ejection fraction < 45% by multi gated acquisition scan (MUGA), ECG, or cardiac magnetic resonance imaging (MRI)\r\n* A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), torsades de pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD)\r\n* Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes\r\n* Uncontrolled hypertension, i.e., blood pressure (BP) of >= 170/95; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria\r\n* Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)
Any known cardiac abnormalities such as:\r\n* Congenital long QT syndrome\r\n* Corrected QT (QTc) interval >= 500 milliseconds;\r\n* Myocardial infarction within 6 months of cycle 1, day 1 (C1D1); subjects with a history of myocardial infarction between 6 and 12 months prior to C1D1 who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event may participate;\r\n* Other significant electrocardiogram (ECG) abnormalities including second (2nd) degree atrio-ventricular (AV) block type II, third (3rd) degree AV block, or bradycardia (ventricular rate less than 50 beats/min);\r\n* Symptomatic coronary artery disease (CAD), e.g., angina; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;\r\n* An ECG recorded at screening showing evidence of cardiac ischemia (ST depression, depression of >= 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;\r\n* Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II to IV definitions and/or ejection fraction < 40% by multi gated acquisition scan (MUGA) scan or < 50% by echocardiogram and/or magnetic resonance imaging (MRI);\r\n* A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), torsade de pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD);\r\n* Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes;\r\n* Uncontrolled hypertension, i.e., blood pressure (BP) of >= 160/95; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria; or\r\n* Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)
Patient has any of the following cardiac abnormalities:symptomatic congestive heart failure, history of documented congestive heart failure (New York Heart Association functional classification III-IV), documented cardiomyopathy, Left Ventricular Ejection Fraction (LVEF) <50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO); myocardial infarction ? 6 months prior to enrolment, unstable angina pectoris, serious uncontrolled cardiac arrhythmia, symptomatic pericarditis, QTcF > 480 msec on the screening ECG (using the QTcF formula);
Patients with risk factors for torsades de pointes, including uncorrected hypokalemia, uncorrected hypomagnesemia, family history of long QT syndrome, clinically significant/symptomatic bradycardia, high-grade atrio-ventricular (AV) block, autonomic neuropathy (including that caused by diabetes or Parkinson’s disease, uncontrolled hypothyroidism, cirrhosis, or the use of concomitant medications known to prolong the QT interval)
Patient has any of the following cardiac abnormalities:\r\n* Symptomatic congestive heart failure\r\n** History of documented congestive heart failure (New York Heart Association functional classification III-IV), documented cardiomyopathy\r\n** Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* Myocardial infarction =< 6 months prior to enrollment\r\n* Unstable angina pectoris\r\n* Serious uncontrolled cardiac arrhythmia\r\n* Symptomatic pericarditis\r\n* Corrected QT interval using Fridericia's formula (QTcF) > 480 msec on the screening electrocardiogram (ECG) (using the QTcF formula)\r\n* Currently receiving treatment with medication that has a known risk to prolong the QT interval or inducing Torsades de Pointes, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug
Significant active cardiovascular or pulmonary disease including:\r\n* Uncontrolled hypertension (i.e., systolic blood pressure > 180 mmHg, diastolic blood pressure > 95 mmHg); use of anti-hypertensive agents to control hypertension before cycle 1 day 1 is allowed\r\n* Pulmonary hypertension\r\n* Uncontrolled asthma or oxygen (O2) saturation < 90% by arterial blood gas analysis or pulse oximetry on room air\r\n* Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement\r\n* History of arrhythmia requiring an implantable cardiac defibrillator\r\n* Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiogram (ECG) e.g. medically significant (symptomatic) bradycardia, complete left bundle branch block, third degree heart block and second-degree heart block or history of arrhythmia requiring an implantable cardiac defibrillator; or within the last 6 months before administration of the first dose of drug:\r\n** Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)\r\n** Placement of a pacemaker for control of rhythm\r\n** Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures\r\n** Ischemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures\r\n** New York Heart Association (NYHA) class III or IV heart failure\r\n** Pulmonary embolism\r\n* Baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTcF >= 470 msec (mean value) obtained from 3 ECGs, using the screening clinic ECG machine derived QTc value, or history of congenital long QT syndrome, or torsades de pointes); any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval\r\n* Left ventricular ejection fraction (LVEF) by either multigated acquisition (MUGA) or echocardiography (ECHO) less than lower limit of normal
Any known cardiac abnormalities such as:\r\n* Congenital long QT syndrome\r\n* QTc interval >= 480 milliseconds;\r\n* Myocardial infarction within 6 months of course 1, day 1 (C1D1); subjects with a history of myocardial infarction between 6 and 12 months prior to C1D1 who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event may participate;\r\n* Other significant electrocardiogram (ECG) abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min);\r\n* Symptomatic coronary artery disease (CAD), e.g., angina Canadian class II-IV; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;\r\n* An ECG recorded at screening showing evidence of cardiac ischemia (ST depression of >= 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;\r\n* Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II to IV definitions and/or ejection fraction < 40% by multi gated acquisition (MUGA) scan or < 50% by echocardiogram and/or magnetic resonance imaging (MRI);\r\n* A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD);\r\n* Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other cause;\r\n* Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)
Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality including any of the following:\r\n* History of angina pectoris, symptomatic pericarditis, coronary artery bypass graft (CABG) or myocardial infarction within 6 months prior to study entry\r\n* Documented cardiomyopathy\r\n* Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) detected during screening\r\n* History of cardiac failure, significant/symptomatic bradycardia, long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome or any of the following:\r\n** Known risk to prolong the QT interval or induce torsade’s de pointes\r\n** Uncorrected hypomagnesemia or hypokalemia\r\n** Systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg\r\n** Bradycardia (heart rate < 50 at rest), by electrocardiogram (ECG) or pulse\r\n** On screening, inability to determine the corrected QT using Fridericia's formula (QTcF) interval on the ECG (i.e.: unreadable or not interpretable) or QTcF > 450 screening ECG (based on a mean of 3 ECGs)
No history of cornea abnormalities
Significant abnormalities on ECG at Screening
Have major abnormalities documented by ECHO with Doppler:
Any of the following laboratory abnormalities:
Has ECG abnormalities that make QT interval corrected (QTc) evaluation difficult (e.g., severe morphologic abnormalities).
Significant screening ECG abnormalities.
Significant ECG abnormalities.
Patients excluded for laboratory abnormalities or performance score ONLY may be enrolled on the study with the approval of the PI or designee
Any of the following laboratory abnormalities:
Significant screening ECG abnormalities
Significant cardiac abnormalities
CNS abnormalities
Gastrointestinal abnormalities including but not limited to:
Has gastrointestinal abnormalities including:
Certain cardiac abnormalities or history
History or presence of bradydysrhythmia or conduction abnormalities
Patients with the following laboratory abnormalities:
Significant cardiac abnormalities;
Significant laboratory abnormalities;
Any of the following cardiac abnormalities or history
Subject has t(8;21), inv(16), t(16;16) or t(15;17) karyotype abnormalities.
Any of the following laboratory abnormalities:
Any of the following laboratory abnormalities:
Significant serum chemistry abnormalities
ECG abnormalities as defined by the protocol
Cardiac abnormalities
Cardiac abnormalities
Anyone with cardiac abnormalities or history
Any of the following laboratory abnormalities:
Patients with uncorrectable electrolyte abnormalities.
Patients must have a normal baseline ophthalmologic examination or have only clinically-insignificant abnormalities; patients with significant visual/ocular abnormalities identified during the baseline eye exam may be eligible after discussion with the study principal investigator (PI) and it is thought that the abnormalities pose no increased risk with study therapy
Any laboratory abnormalities, which in the opinion of the investigator, may put the subject at risk if participating in the study; for example:
De novo AML with karyotypic abnormalities characteristic of MDS: de novoAML must have cytogenetics with abnormalities per WHO.
No significant hematologic abnormalities
Any of the following laboratory abnormalities:
Have major abnormalities documented by echocardiography with Doppler
Any of the following laboratory abnormalities:
Significant ECG abnormalities.
Cardiac abnormalities
DONOR: No evidence of significant liver abnormalities
Any grade 4 laboratory abnormalities
Patient has any of the following cardiac abnormalities:
Any of the following laboratory abnormalities:
Cardiac abnormalities:
Cardiovascular abnormalities:
The history or evidence of following cardiac abnormalities:
Patients with any of the following hematologic abnormalities at baseline:
Patients with any of the following serum chemistry abnormalities at baseline:
PART I: Subjects with evidence of cardiac toxicity and Q wave abnormalities at baseline electrocardiography (ECG) will not be allowed to participate
PART II: Subjects with evidence of cardiac toxicity and Q wave abnormalities at baseline ECG will not be allowed to participate
Patients with any of the following hematologic abnormalities at baseline:
Patients with any of the following serum chemistry abnormalities at baseline:
Any of the following laboratory abnormalities:
Certain cardiac abnormalities.
Any of the following laboratory abnormalities:
History or evidence of cardiac abnormalities.
12-lead electrocardiogram (ECG) showing normal heart rhythm; note: if there are abnormalities, then the abnormalities must be deemed of no clinical significance
Any of the following laboratory abnormalities:
has following laboratory abnormalities
At least two manifestations drawn from at least two of the categories (clinical symptoms, laboratory abnormalities and radiographic abnormalities), which are at least possibly attributable to KICS and are not readily explicable from known medical conditions in the patient
LABORATORY ABNORMALITIES
RADIOGRAPHIC ABNORMALITIES
Any of the following laboratory abnormalities at Screening: