A history of any of the following: sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes, cardiac arrest, Mobitz II second degree heart block or third degree heart block; known presence of dilated, hypertrophic, or restrictive cardiomyopathy
Have documented major electrocardiogram (ECG) abnormalities which are clinically significant at the investigator's discretion (for example, symptomatic or sustained atrial or ventricular arrhythmias, second- or third-degree atrioventricular block, bundle-branch blocks, ventricular hypertrophy, or recent myocardial infarction).
Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree AV block type II, 3rd degree block, bradycardia, or corrected QT interval (Fridericia’s correction; QTcF) > 470 msec
History or family history of Long QT Syndrome or Torsade de Pointes. Myocardial infarction, CABG, coronary or cerebral artery stenting and /or angioplasty, stroke, cardiac surgery, or hospitalization for congestive heart failure within 3 months or greater than Class 2 Angina Pectoris or NYHA Heart Failure Class >2. QTcF > 470 msec, PR > 280 msec, Mobitz II 2nd degree AV Block, 2:1 AV Block, High Grade AV Block, or Complete Heart Block, unless the patient has an implanted pacemaker or implantable cardiac defibrillator (ICD) with backup pacing capabilities.
For Part G: Have a baseline electrocardiogram (obtained from Day -14 to Day -1) with any of the following abnormal findings: ventricular arrhythmia, evidence of acute myocardial ischemia, heart block (of any degree), or QTc prolongation (defined as QTcB ?450 milliseconds).
Patient with severe conduction disorders which are not prevented by permanent pacing (atrio-ventricular block 2 and 3, sino-atrial block)
QTc prolongation (defined as a QTc > 450 msecs) or other significant ECG abnormalities including 2nd degree atrioventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats per minute [bpm]). If the screening ECG has a QTc > 450 msecs, the ECG can be submitted for a centralized, cardiologic evaluation.
No evidence of PR prolongation or atrioventricular (AV) block on baseline electrocardiogram (ECG)
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)
CRITERIA SPECIFIC FOR COHORT #2 (MCL): Significant screening electrocardiogram (ECG) abnormalities including, but not limited to, left bundle branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block, or corrected QT interval (QTc) >= 470 msec; subjects with a cardiac pacemaker who have a QTc interval of >= 470msec may be eligible if these findings are considered not clinically significant as documented via a cardiology evaluation
Significant screening ECG abnormalities, including unstable cardiac arrhythmia requiring medication, atrial fibrillation/flutter, left bundle branch block, 2nd-degree atrioventricular (AV) block type II, 3rd degree AV block, Grade ?2 bradycardia, or corrected QT (QTc) >450 msec (for men) or >470 msec (for women).
Subjects with a history of significant cardiac disease including: congestive heart failure requiring therapy; history of myocardial infarction (MI), angina pectoris, coronary artery bypass graft (CABG) within 6 months prior to starting study treatment; clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third degree AV block); left ventricular ejection fraction (LVEF) < 50% evaluated by echocardiogram (ECHO) or multigated acquisition scan (MUGA); increased Fridericia's correction formula (QTcF) (> 450 for men and > 470 for women).
Clinically significant 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).
Significant screening electrocardiogram (ECG) abnormalities including, but not limited to, left bundle branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block, or corrected QT interval (QTc) >= 470 msec; subjects with a cardiac pacemaker who have a QTc interval of >= 470 msec may be eligible if these findings are considered not clinically significant as documented via a cardiology evaluation
Significant screening electrocardiogram (ECG) abnormalities including, but not limited to, left bundle branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block, or corrected QT interval (QTc) >= 470 msec; subjects with a cardiac pacemaker who have a QTc interval of >= 470 msec may be eligible if these findings are considered not clinically significant as documented via a cardiology evaluation
Significant screening ECG abnormalities, including unstable cardiac arrhythmia requiring medication, atrial fibrillation/flutter, left bundle-branch block, 2nd-degree atrioventricular (AV) block type II, 3rd degree AV block, Grade ?2 bradycardia, or QT corrected for heart rate (QTc) >450 msec (for men) or >470 msec (for women).
Significant screening electrocardiogram (ECG) abnormalities including, but not limited to, left bundle branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block, or corrected QT interval (QTc) >= 470 msec; subjects with a cardiac pacemaker who have a QTc interval of >= 470 msec may be eligible if these findings are considered not clinically significant as documented via a cardiology evaluation
Patients with a history of PR prolongation or atrioventricular (AV) block
Other significant electrocardiogram (EKG) abnormalities including second (2nd) degree atrio-ventricular (AV) block type II, third (3rd) degree AV block, or bradycardia (ventricular rate less than 50 beats/min)
Patients with New York Heart Association (NYHA) class III and IV heart failure, myocardial infarction in the preceding 6 months, and significant conduction abnormalities, including but not limited to 2nd degree atrioventricular block (AV block) type II, 3rd degree block, QT prolongation (corrected QT [QTc] > 500 millisecond [msec]), sick sinus syndrome, ventricular tachycardia, symptomatic bradycardia (heart rate < 50 beats per minute [bpm]), hypotension, light headedness and syncope; patients with persistent and uncontrolled atrial fibrillation will be excluded; the protocol excludes patients who have recently had a stent and by recommendation of their cardiologist need to stay on anticoagulants such as warfarin or equivalent vitamin K antagonist
History of significant cardiac disease defined as:\r\n* Symptomatic congestive heart failure (CHF) (New York Heart Association [NYHA] classes III-IV)\r\n* High-risk uncontrolled arrhythmias; i.e. atrial tachycardia with a heart rate > 100/min at rest, significant ventricular arrhythmia or higher-grade atrioventricular (AV) block (second degree AV-block type 2 [mobitz 2] or third degree AV-block)\r\n* Prolongation of QT interval > 480 msecs\r\n* History of myocardial infarction within last 12 months\r\n* Clinically significant valvular heart disease\r\n* Angina pectoris requiring anti-angina treatment\r\n* Current uncontrolled hypertension (persistent systolic > 180 mmHg and/or diastolic > 100 mmHg); initiation or adjustment of anti-hypertensive medication is permitted prior to study entry
Relapsed/refractory MCL: Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block, bradycardia (< 50 beats per minute [bpm]), or corrected QT (QTc) > 500 msec
Newly diagnosed MCL: Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree AV block type II, 3rd degree block, bradycardia (< 50 bpm), or QTc > 500 msec
Patient with evidence of clinically significant bradycardia (heart rate [HR] < 50), or a history of clinically significant bradyarrhythmias such as sick sinus syndrome, 2nd degree atrioventricular (AV) block (Mobitz type 2), patient with uncontrolled hypertension (>= 140/90 mmHg). Patients who are controlled on antihypertensive medication will be allowed to enter the study
History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place
High-grade (second degree or above) atrioventricular (AV) block or persistent sinus bradycardia of less than 50 beats per minute (BPM)
Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular block (AV block) type II, 3rd degree block, bradycardia (< 50 beats per minute [bpm]), or corrected QT (QTc) > 500 msec.
Risk factors for Torsades de Pointes such as hypokalemia, hypomagnesemia, cardiac failure, clinically significant/symptomatic bradycardia, or high-grade atrioventricular (AV) block
Subject with clinically significant cardiac arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes, second degree or third degree atrioventricular heart block without a permanent pacemaker in place)
Clinically significant cardiovascular disease (that is, active or <3 months prior to enrollment): cerebral vascular accident/stroke, myocardial infarction, unstable angina, congestive heart failure (New York Heart Association Classification Class ? II), second-degree or third-degree AV block (unless paced) or any AV block with PR >220 msec. Ongoing cardiac dysrhythmias of NCI CTCAE Grade ?2, uncontrolled atrial fibrillation of any grade, bradycardia defined as <50 bpm (unless patient is otherwise healthy such as long-distance runners, etc.), machine-read ECG with QTc >470 msec, or congenital long QT syndrome.
QTcF prolongation defined as a QTcF interval >470 msec or other significant ECG abnormalities including 2nd degree (type II) or 3rd degree AV block or bradycardia (ventricular rate <50 beats/min).
History of torsades de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia (< 50 bpm), heart block (excluding first degree block, being PR interval only), or congenital long QT syndrome. Patients with a history of atrial arrhythmias should be discussed with the Medical Monitor.
History of torsades de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia (< 50 bpm), heart block (excluding first degree block, being PR interval only), or congenital long QT syndrome. Subjects with a history of atrial arrhythmias should be discussed with the medical monitor
Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular (AV) block, type II AV block, or 3rd degree block
Wolff-Parkinson White syndrome or first/second/third degree atrioventricular (AV) block or sinus node dysfunction or the presence of an intra-cardiac defibrillator
have documented major electrocardiogram (ECG) abnormalities (not responding to medical treatments) at the investigator's discretion (for example, symptomatic or sustained atrial or ventricular arrhythmias, second- or third-degree atrio ventricular block, complete bundle branch block, ventricular hypertrophy, or recent myocardial infarction).
Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular (AV) block, type II AV block, or 3rd degree block
History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place.
Patients with New York Heart Association (NYHA) class III and IV heart failure, myocardial infarction in the preceding 6 months, and significant conduction abnormalities, including but not limited to second (2nd) degree atrioventricular (AV) block type II, third (3rd) degree block, QT prolongation (corrected QT [QTc] > 500 msec), sick sinus syndrome, ventricular tachycardia, symptomatic bradycardia (heart rate < 50 beats per minute [bpm]), hypotension, light headedness and syncope; patients with active atrial fibrillation will be excluded; the protocol excludes patients who have within the past year had a stent and by recommendation of their cardiologist need to stay on anticoagulants such as warfarin equivalent vitamin K antagonist
Other significant electrocardiogram (ECG) abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block
Any history of second- or third-degree heart block. (Patients with pacemakers may be eligible.)
Inability to determine the QTcF interval Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block).
Patients with New York Heart Association (NYHA) class III and IV heart failure, myocardial infarction in the preceding 6 months, and significant conduction abnormalities, including but not limited to atrial fibrillation, 2nd degree atrioventricular (AV) block type II, 3rd degree block, torsades de pointes, QT prolongation (corrected QT [QTc] > 450 msec), sick sinus syndrome, ventricular tachycardia, symptomatic bradycardia (heart rate < 50 beats per minute [bpm]), hypotension, light headedness and syncope; patients with atrial fibrillation will be excluded even if they are rate-controlled; if there are any active cardiac issues, cardiology consultation will be obtained for clearance
Significant screening ECG abnormalities including left bundle branch block, 2nd degree AV block type II, 3rd degree block, Grade 2 or higher bradycardia, and QTc > 480 msec.
Significant screening ECG abnormalities including left bundle branch block, 2nd degree AV block type II, 3rd degree block, Grade 2 or higher bradycardia, and QTc ? 480 ms.
Adequate cardiac conduction by ECG without evidence of second- or third-degree atrioventricular block and meeting all of the following ECG criteria:
No evidence of second- or third-degree atrioventricular block
First degree atrioventricular (AV) block on ECG in which PR interval lengthened > 200 milliseconds; second degree; or third degree
Other clinically significant ECG abnormalities including 2nd degree (Type II) or 3rd degree atrioventricular (AV) block.
Severe sinus bradycardia; heart block, second or third degree or sick sinus syndrome (if no artificial pacemaker present)
Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class IIIB or IV heart failure uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities (not including 1st degree atrioventricular (AV)-block, Wenckebach type 2nd degree heart block, or left bundle branch block; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be evaluted by the investigator or an authorized physician sub-investigator); note: there is no lower limit of left ventricular ejection fraction below which patients are excluded from participation
Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block, or corrected QT interval (QTc) >= 470 msec
Patients with any clinically significant cardiovascular disease including the following:\r\n* Myocardial infarction or ventricular tachyarrhythmia within 6 months\r\n* Prolonged QTc > 480 msec by the Fridericia correction\r\n* Major conduction abnormality, such as 2nd or 3rd degree heart block or symptomatic bundle branch block, unless a cardiac pacemaker is present
First degree atrioventricular (AV) block
Second degree AV block Type 1 (Mobitz Type 1/ Wenckebach type)
History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place.
Clinically relevant findings in the ECG such as a second-degree or third-degree atrioventricular (AV) block (subjects with AV block and pacemaker in place for >1 year and checked by a cardiologist within ?6 months before the first dose of study drug will not be excluded), prolongation of the QRS complex over 120 msec or of the QTc interval (Fridericia, QTcF) over 470 msec (subjects with a pacemaker and QRS interval over 120 msec or QTc inverval over 470 msec may be enrolled on a case-by-case basis, following a discussion between the investigator and the sponsor).
Patients with second (2nd) or third (3rd) degree atrioventricular (AV) block
AV block (other than 1o AV Block with PR > 200 msec)
History of torsade de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia (<60 bpm), heart block (excluding 1st degree block, being PR interval prolongation only), congenital long QT syndrome or new ST segment elevation or depression or new Q wave on ECG
Other significant electrocardiogram (EKG) abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min)
Grade 2 or 3 atrioventricular (AV) block (Mobitz type I is permitted) or sick sinus syndrome, unless subject has a pacemaker
History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place
Any history of second or third degree heart block;
Patients with sick-sinus syndrome, sino-atrial block, third degree heart block, atrial fibrillation, and those with permanent pacemakers
Patients must not have history of or presence of Mobitz type II 2nd degree or 3rd degree atrioventricular block or sick sinus syndrome, unless patient has a pacemaker
Sustained or symptomatic ventricular dysrhythmias uncontrolled with drug therapy or implantable device; significant conduction defects (i.e.: second or third degree atrio-ventricular block or sick sinus syndrome)
Allergies or inability to tolerate beta blockers previously due to bradycardia, hypotension, or atrioventricular (AV) block
History of second (Mobitz II) or third degree heart block (subjects with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker);
Second (2nd) or third (3rd) degree heart block as assessed by preoperative electrocardiogram (EKG)
Significant conduction defects (i.e. second or third degree atrio-ventricular block or sick sinus syndrome)
Second- or third-degree atrioventricular (AV) block
Have documented major electrocardiogram (ECG) abnormalities (not responding to medical treatments) at the investigator's discretion (for example, symptomatic or sustained atrial or ventricular arrhythmias, second- or third-degree atrioventricular block, complete bundle branch block, ventricular hypertrophy, or recent myocardial infarction).
Documented left ventricular ejection fraction (LVEF) of less than or equal to 45% tested; the following patients will undergo cardiac evaluations:\r\n* Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or\r\n* Age >= 60 years old
Documented left ventricular ejection fraction (LVEF) of less than or equal to 45% tested; the following patients will undergo cardiac evaluations\r\n* Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or\r\n* Age >= 60 years old
Documented LVEF of less than or equal to 45% tested in patients with i) clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or ii) age >= 60 years old
Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation, and ventricular tachycardia)
No history of arrhythmia (multifocal premature ventricular contractions [PVCs], bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (Common Terminology Criteria for Adverse Events [CTCAE] grade 3) or asymptomatic sustained ventricular tachycardia; atrial fibrillation, controlled on medication is permitted
Significant, uncontrolled cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation, or ventricular tachycardia).
Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation, or ventricular tachycardia).
Unstable ventricular tachycardia or fibrillation
History of any of the following within the last 6 months prior to study entry: requirement of inotropic support; serious uncontrolled cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia); placement of a pacemaker for control of rhythm
History or presence of atrial fibrillation , atrial flutter or paroxysmal supraventricular tachycardia; the presence or history of ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia
History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia; patients with atrial fibrillation controlled by medication are permitted
History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (Common Terminology Criteria for Adverse Events [CTCAE] grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia; patients with atrial fibrillation controlled by medication are permitted
Presence of any of the following on electrocardiogram (ECG):\r\n* Atrial arrhythmias, including atrial fibrillation and flutter\r\n* Atrioventricular (AV) block\r\n* Heart rate < 60 beats/minute unless the participant is otherwise eligible, without significant cardiac concerns and approval is obtained by the protocol chair/study cardiologist prior to enrollment\r\n* Heart rate > 100 beats/minute\r\n* Ventricular fibrillation\r\n* Ventricular tachycardia\r\n* Premature ventricular contractions\r\n* Wolff-Parkinson-White syndrome\r\n* NOTE: any questions on cardiac eligibility should be reviewed by the Study Cardiologist for approval in advance of enrollment
Patient must not have ongoing ventricular cardiac dysrhythmias of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4 grade > 2; patients with a history of serious ventricular arrhythmia (ventricular tachycardia [VT] or ventricular fibrillation [VF] > 3 beats in a row) are also excluded; additionally, patients with ongoing atrial fibrillation are not eligible
Have a personal history of any of the following conditions: syncope of either unexplained or cardiovascular etiology, ventricular arrhythmia (including but not limited to ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest. Exception: Participants with controlled atrial fibrillation for >30 days prior to study treatment initiation are eligible.
Requirement for inotropic support (excluding digoxin), or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation, or ventricular tachycardia);
History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or serious cardiac arrhythmia requiring medication. This does not include asymptomatic atrial fibrillation with controlled ventricular rate.
Have a personal history of any of the following conditions: presyncope or syncope of either unexplained or cardiovascular etiology, ventricular arrhythmia (including but not limited to ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest. Exception: Participants with controlled atrial fibrillation for >30 days prior to study treatment are eligible.
Participants with a history of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, uncontrolled atrial fibrillation, left bundle branch block) that is symptomatic or requires treatment (except for controlled atrial fibrillation)
History of arrhythmia (multifocal premature ventricular contractions PVCs), bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia; atrial fibrillation, controlled on medication, is not excluded
Patients with a history of arrhythmia or asymptomatic sustained ventricular tachycardia are not eligible. Patients with atrial fibrillation with well-controlled ventricular rate on medication, are eligible.
Significant ventricular arrhythmias (> 20 premature ventricular contractions [PVCs]/min due to gating difficulty) atrial fibrillation with uncontrolled ventricular response
History of arrhythmia (multifocal premature ventricular contractions [PVCs], bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation), which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia; atrial fibrillation, controlled on medication is not excluded
Cardiac dysrhythmia that is potentially life-threatening, such as ventricular tachycardia, multifocal premature ventricular contractions or supraventricular tachycardias with a rapid ventricular response; well-controlled atrial fibrillation or rare (< 2 minute) premature ventricular contractions are not exclusionary
Atrial fibrillation with uncontrolled ventricular response
Have a personal history of any of the following conditions: syncope of either unexplained or cardiovascular etiology, ventricular arrhythmia (including but not limited to ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest. Exception: subjects with controlled atrial fibrillation for >30 days prior to study treatment are eligible.
Uncontrolled or significant cardiovascular disease, clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation, or Torsades des pointes), clinically significant pulmonary disease (such as ? Grade 2 dyspnea, according to CTCAE 4.03)
History of ventricular arrhythmia requiring medication
Patients with a history or presence of significant ventricular or atrial tachyarrhythmia are excluded
History or presence of sustained ventricular tachycardia
Any history of ventricular fibrillation or torsades de pointes
Grade ?2 ventricular arrhythmia ?6 months prior to Day 1
Significant ventricular arrhythmia (persistent ventricular tachycardia, ventricular fibrillation, resuscitated sudden death)
History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias
The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest
Persistent or clinically meaningful ventricular arrhythmias.
Hiistory of ventricular arrhythmia
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)
History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias
Patients with a known history of corrected QT (QTc) prolongation (> 480 msec), or known history of ventricular tachycardia, ventricular fibrillation or Torsades de pointes are not eligible
History or presence of sustained bradycardia (?55 BPM), left bundle branch block, cardiac pacemaker or ventricular arrhythmia. Note: Patients with a supraventricular arrhythmia requiring medical treatment, but with a normal ventricular rate are eligible;
Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:\r\n* Myocardial infarction within the past 6 months \r\n* Uncontrolled angina within the past 6 months \r\n* Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation or Torsades de pointes); controlled atrial fibrillation by itself is not an exclusion criterion
A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), torsade de pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter-defibrillator (AICD)
Any history of clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation or torsade de pointes)
Unstable ventricular arrhythmia requiring treatment
Uncontrolled or significant cardiovascular disease, clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes), clinically significant pulmonary disease (such as ? Grade 2 dyspnea, according to CTCAE 4.03).
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)
History of sustained ventricular tachycardia
Any history of ventricular fibrillation or torsades de pointes
Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
Cardiac disease including: uncontrolled angina within 3 months; diagnosed or suspected congenital long QT syndrome; any history of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or Torsades de pointes); prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (> 470 msec) on the Fridericia's correction; uncontrolled hypertension (defined for this protocol as sustained systolic blood pressure [BP] >= 150 and diastolic >= 100); patients currently taking drugs that are generally accepted to have a risk of causing Torsades de pointes
History of clinically significant ventricular arrhythmias
Any history of ventricular arrhythmia; or
History of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation or Torsades de Pointes);
History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsade de pointes);
History of serious ventricular arrhythmia (ventricular tachycardia [VT] or ventricular fibrillation [VF], greater than or equal to 3 beats in a row); QTc greater than or equal to 450 msec for men and 470 msec for women; or left ventricular ejection fraction (LVEF) less than or equal to 40% by multi-gated acquisition scan (MUGA).
History or presence of clinically significant ventricular or atrial tachyarrhythmias, or cardiac arrest
Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, congenital long QT syndrome, or torsades de pointes)
history within the last 12 months of any of the following conditions: syncope of cardiovascular etiology, ventricular tachycardia, ventricular fibrillation, or sudden cardiac arrest
Have a personal history of any of the following conditions: presyncope or syncope of either unexplained or cardiovascular etiology, ventricular arrhythmia (including but not limited to ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:\r\n* Myocardial infarction within the past 6 months\r\n* Uncontrolled angina within the past 6 months\r\n* Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation or Torsades de pointes); controlled atrial fibrillation by itself is not an exclusion criterion\r\n* Baseline corrected QT (QTc) interval greater than 500 milliseconds
Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
Have a personal history of any of the following conditions: syncope of either unexplained or cardiovascular etiology, ventricular tachycardia, ventricular fibrillation, or sudden cardiac arrest.
History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, Torsade de Pointes).
Any of the following within 6 months before the first dose of study treatment:\r\n* Unstable angina pectoris\r\n* Clinically-significant cardiac arrhythmias\r\n* Stroke (including transient ischemic attack [TIA], or other ischemic event)\r\n* Myocardial infarction\r\n* Thromboembolic event requiring therapeutic anticoagulation (Note: subjects with a venous filter [e.g. vena cava filter] are not eligible for this study)\r\n* Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes)\r\n* Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec), may use either the Fridericia and Bazett’s correction\r\n* Hypokalemia or hypomagnesemia that is not corrected prior to dasatinib administration\r\n* Patients should not be taking drugs that are generally accepted to have a risk of causing torsades de pointes; the following must be discontinued at least 7 days prior to starting dasatinib to be eligible: quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, erythromycins, clarithromycin, chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine
A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), torsade de pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD)
Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, Wolff-Parkinson-White [WPW] syndrome, or torsade de pointes), or prolonged QTc interval on pre-entry ECG (>450 msec). If the automated reading is prolonged (i.e., >450 msec), the ECG should be manually over-read.
No history of sustained ventricular tachycardia (lasting longer than 30 sec) or cardiac arrest
Have a personal history within the last 12 months of any of the following conditions: syncope of cardiovascular etiology, ventricular tachycardia, ventricular fibrillation, or sudden cardiac arrest
Any history of ventricular arrhythmia
Unacceptable cardiac risk factors defined by any of the following criteria: patients with congenital long QT syndrome, any history of ventricular fibrillation or torsade de pointes, bradycardia defined as heart rate (HR) < 50 bpm, left ventricular ejection fraction < 30%
Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes);
PART B: Any history of ventricular arrhythmia (other than premature ventricular complexes)
Ventricular shunt/catheter
Concurrent medical condition which may increase the risk of toxicity, including:\r\n* Pleural or pericardial effusion of any grade at the time of screening for study\r\n* Cardiac symptoms; any of the following should be considered for exclusion:\r\n** Uncontrolled angina, congestive heart failure or myocardial infarction (MI) within (6 months)\r\n** Diagnosed congenital long QT syndrome\r\n** Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
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)
Any history of ventricular fibrillation or torsade de pointes
Have a personal history of any of the following conditions: presyncope or syncope of either unexplained or cardiovascular etiology, ventricular arrhythmia (including but not limited to ventricular tachycardia and ventricular fibrillation), sudden cardiac death or sudden cardiac arrest
History of clinically significant ventricular arrhythmias or active ventricular arrhythmia requiring medication
High-risk uncontrolled arrhythmias (ventricular tachycardia, high-grade atrio-ventricular [AV]-block, supraventricular tachycardias which are not adequately rate-controlled)
History or presence of sustained ventricular tachyarrhythmia (patients with a history of atrial arrhythmia are eligible but should be discussed with the study principal investigator [PI] prior to enrollment)
Any history of ventricular fibrillation or torsade de pointes
History of Torsades de pointes, ventricular tachycardia, or ventricular fibrillation
History of Torsades de pointes, ventricular tachycardia, or ventricular fibrillation
Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
Active Grade III-V cardiac failure as defined by the New York Heart Association Criteria. Uncontrolled angina, or MI within 6 months. Diagnosed or suspected congenital long QT syndrome. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes). Prolonged QTc interval on pre-entry electrocardiogram (> 470 msec). Patients currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes (unless these can be changed to acceptable alternatives)
Persistent or clinically meaningful ventricular arrhythmias
History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes);
Any of the following related to risk of torsades de pointes and sudden cardiac death:\r\n* History of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), torsades de pointes, or resuscitated cardiac arrest unless currently addressed with an implanted cardiac defibrillator\r\n* Concomitant treatment with an anti-arrhythmic agent to prevent or control arrhythmia; agents used for rate-control of atrial fibrillation are permitted provided that they are not prohibited due to potential drug interactions\r\n* Known congenital long QT syndrome\r\n* Second degree atrioventricular (AV) block type II, third degree AV block, or ventricular rate < 50 bpm or > 120 bpm
History or presence of sustained ventricular tachyarrhythmia (patients with a history of atrial arrhythmia are eligible but should be discussed with the Novartis prior to enrollment)
Any history of ventricular fibrillation or torsade de pointes
History or presence of sustained ventricular tachyarrhythmia. (Patients with a history of atrial arrhythmia are eligible but should be discussed with the study chair prior to enrollment).
Any history of ventricular fibrillation or torsade de pointes.
History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation)
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)
Need for antiarrhythmic medical therapy for a ventricular arrhythmia
Known history of sustained (> 30 second) ventricular tachycardia or cardiac syncope. Known history of recurrent non-sustained ventricular tachycardia (> 3 beats) despite anti-arrhythmic therapy
History or presence of ventricular tachyarrhythmia
History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsade de pointes)
Uncontrolled angina or uncontrolled hypertension or any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
History or presence of ventricular tachyarrhythmia
Active ventricular arrhythmia requiring medication
Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes [TdP]);
Patients who have a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological original (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest
History of clinically relevant ventricular arrhythmias (eg, ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes);
History or presence of sustained ventricular tachycardia
Any history of ventricular fibrillation or torsades de pointes
Significant ventricular arrhythmias (> 20 premature ventricular contractions [PVCs]/minute due to gating difficulty)
Patients with clinically unstable cardiac arrhythmias, such as recurrent ventricular tachycardia
Documented LVEF of less than or equal to 45% tested in patients with:\r\n* Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or have a history of ischemic heart disease, chest pain\r\n* Age >= 65 years old
Documented LVEF of less than or equal to 45%, note: testing is required in patients with:\r\n* Age >= 65 years old\r\n* Clinically significant atrial and or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block, or history of ischemic heart disease or chest pain
Documented left ventricular ejection fraction (LVEF) of less than or equal to 45% tested in patients with:\r\n* Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block, chest pain, or ischemic heart disease\r\n* Age >= 65 years old
Documented LVEF of less than or equal to 45% tested in patients with:\r\n* Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or have a history of ischemic heart disease, chest pain\r\n* Age >= 65 years old
Documented left ventricular ejection fraction (LVEF) =< 45% tested in patients:\r\n* Age >= 65 years\r\n* With clinically significant atrial and/or ventricular arrhythmias, including but not limited to: atrial fibrillation, ventricular tachycardia, second- or third-degree heart block, or have a history of ischemic heart disease and/or chest pain.
Documented LVEF =< 45% tested in patients with:\r\n* Age >= 65 years\r\n* With clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second- or third-degree heart block or have a history of ischemic heart disease and/or chest pain
Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%; testing is required in patients with:\r\n* Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or have a history of ischemic heart disease or chest pain\r\n* Age >= 65 years’ old
Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%; testing is required in patients with:\r\n* Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or have a history of ischemic heart disease, or chest pain\r\n* Age >= 65 years old\r\n* Prior treatment with significant exposure to anthracyclines or cyclophosphamide
Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%; testing is required in patients with:\r\n* Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block\r\n* Age >= 60 years old
Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%; note: testing is required in patients with:\r\n* Age >= 65 years old\r\n* Clinically significant atrial and or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or have a history of ischemic heart disease, chest pain
Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%; testing is required in patients who are:\r\n* Age >= 65 years old\r\n* Clinically significant atrial and or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or have a history of ischemic heart disease, or chest pain
Documented left ventricular ejection fraction (LVEF) of less than or equal to 45% testing is required in patients who are\r\n* >= 65 years old\r\n* Clinically significant atrial and or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or have a history of ischemic heart disease, or chest pain
Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%; testing is required in patients with:\r\n* Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block, chest pain, or ischemic heart disease\r\n* Age >= 65 years old
Documented LVEF =< 45% tested in patients:\r\n* Age >= 65 years\r\n* With clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second-or third-degree heart block or have a history of ischemic heart disease and/or chest pain
Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%; note: testing is required in patients with:\r\n* Age >= 65 years’ old\r\n* Clinically significant atrial and or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or have a history of ischemic heart disease, chest pain
The following patients will be excluded from the high-dose aldesleukin arm (but may be eligible for cells alone arm):\r\n* History of coronary revascularization or ischemic symptoms\r\n* Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%; testing is required in patients with:\r\n** Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block\r\n** Age >= 60 years' old\r\n* Clinically significant patient history which in the judgment of the principal investigator would compromise the patient’s ability to tolerate aldesleukin
Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%, testing is required in patients with:\r\n* Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block\r\n* Age >= 60 years old
Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%; testing is required in patients with:\r\n* Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block\r\n* Age >= 60 years old
Documented left ventricular ejection fraction (LVEF) of less than 45% tested in patients with:\r\n* History of ischemic heart disease, chest pain, or clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block\r\n* Age greater than or equal to 60 years old
Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%, testing is required in patients with:\r\n* Age >= 60 years old\r\n* Clinically significant atrial and or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block
Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%; testing is required in patients with:\r\n* Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block\r\n* Age >= 60 years old