Patients with a history of congestive heart failure (CHF) or are at risk because of underlying cardiovascular disease or exposure to cardiotoxic drugs must have adequate cardiac function as clinically indicated:\r\n* Corrected QT interval (QTC) =< 480 msec\r\n* Shortening fraction of >= 27% by echocardiogram or ejection fraction of >= 50% by gated radionuclide study
History of non-pharmacologically induced prolonged QTc interval
Corrected QT (QTc) =< 480 msec\r\n* Note: Patients should avoid concomitant medication known or suspected to prolong QTc interval or cause Torsades De Pointes; If possible, alternative agents should be considered\r\n* Patients who are receiving drugs that prolong the QTc are eligible if the drug is necessary and no alternatives are available
Patients with QTc interval > 470 milliseconds
A resting electrocardiogram (EKG) with a corrected QT (QTC) >= 470 msec detected on 2 or more time points within a 2 hour period or family history of long QT syndrome; if the EKG demonstrates QTC >= 470 msec, the patient will only be eligible if a repeat EKG demonstrates QTC =< 470 msec
Correct QT interval (QTc) =< 480 msec; Note: Patients should avoid concomitant medication known or suspected to prolong QTc interval or cause torsades de pointes; if possible, alternative agents should be considered; patients who are receiving drugs that prolong the QTc are eligible if the drug is necessary and no alternatives are available
Prolonged rate corrected QT (QTc) interval < 500 msec
Patients with baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTc interval > 480 milliseconds, or history of congenital long QT syndrome, or torsades de pointes)
Patients must have an electrocardiogram (ECG) within 8 weeks prior to registration to screening step and must meet the following cardiac criteria:\r\n* Resting corrected QT interval (QTc) =< 480 msec\r\n** NOTE: If the first recorded QTc exceeds 480 msec, two additional, consecutive ECGs are required and must result in a mean resting QTc =< 480 msec; it is recommended that there are 10-minute (+/- 5 minutes) breaks between the ECGs\r\n* The following only need to be assessed if the mean QTc > 480 msec\r\n** Check potassium and magnesium serum levels\r\n** Correct any identified hypokalemia and/or hypomagnesemia and may repeat ECG to confirm exclusion of patient due to QTc\r\n** For patients with heart rate (HR) 60-100 beats per minute (bpm), no manual read of QTc is required\r\n** For patients with baseline HR < 60 or > 100 bpm, manual read of QT by trained personnel is required, with Fridericia correction applied to determine QTc\r\n** Patient must not have hypokalemia (value < institutional lower limit of normal)\r\n* No factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval\r\n** NOTE: Patient must be taken off prohibited medication prior to registration to the screening step (Step 0, 2, 4, 6) and remain off these medications thereafter, unless permitted on a subprotocol for the management of treatment related toxicity; patient must be off the drug for at least 5 half-lives prior to registration to the treatment step (Step 1, 3, 5, 7); the medication half-life can be found in the package insert for Food and Drug Administration (FDA) approved drugs
Patients must have corrected QT (QTc) =< 480 msec by electrocardiogram (ECG) (corrected using the Bazett’s formula) within 28 days prior to registration
Patients must have corrected QT (QTc) interval < 500/msec (by Bazett’s formula) on baseline ECG
Resting electrocardiogram (ECG) with corrected QT (QTc) > 470 msec detected on 2 or more time points within a 24 hour period or family history of long QT syndrome; if ECG demonstrates QTc > 470 msec, patient will be eligible only if repeat ECG demonstrates QTc =< 470 msec
Corrected QT interval (QTc) < 480 msec
Corrected QT interval (QTc) < 470 milliseconds (msec) on a 12-lead electrocardiogram (ECG) =< 28 days before registration
Patients with a pre-existing diagnosis of a prolonged QT syndrome (even if corrected QT interval [QTc] is normal at the time of APL diagnosis) are excluded
Patients with a baseline QTc of > 450 msec are excluded; Bazett’s formula is to be used for measurement of the corrected QT interval: the QT interval (msec) divided by the square root of the RR interval (msec)
Corrected QT interval, QTc < 480 msec\r\n* Note: Repeat echocardiogram is not required if echocardiogram was obtained within 21 days of study enrollment
QTc =< 480 msec; Note: Patients with grade 1 prolonged QTc (450- 480 msec) at the time of study enrollment should have correctable causes of prolonged QTc addressed if possible (i.e., electrolytes, medications)
Corrected QT (QTc) interval =< 480 milliseconds
Corrected QT (QTc) interval =< 480 milliseconds; Note: Patients should avoid concomitant medication known or suspected to prolong QTc interval or cause Torsades De Pointes; if possible, alternative agents should be considered; patients who are receiving drugs that prolong the QTc are eligible if the drug is necessary and no alternatives are available
Corrected QT (QTc) interval =< 480 milliseconds
Marked baseline prolongation of QT/corrected QT (QTc) interval (e.g. demonstration of a QTc interval greater than 500 milliseconds)
Prolongation of QTc interval to greater than 480 msec
Corrected QT interval (QTc) on electrocardiogram (EKG) > 480 msec
Patients must not have a history of clinically significant arrhythmia, prolonged corrected QT (QTc) interval, or unexplained syncope not thought to be vasovagal in nature within 6 months prior to registration
Patients with a corrected QT interval (QTc) > 480 msecs are NOT eligible for participation
Corrected QT interval (QTc) > 480 msecs using Bazett’s formula
Screening electrocardiogram (ECG) with a corrected QT interval (QTc) > 450 msec
Resting electrocardiography (EKG) with corrected QT (QTc) > 470 msec or family history of long QT syndrome; if EKG demonstrates QTc > 470 msec, patient will be eligible only if repeat EKG demonstrates QTc ? 470 msec
Corrected QT interval (QTc) > 480 msecs using Bazett’s formula
Family history of long QT syndrome, with a QTc interval greater than (>) 480 millisecond (msec) at screening, or taking concurrent medications known to prolong QT/QTc interval
Baseline corrected QT interval (QTc) =< 450 msec\r\n* Note: QT interval calculation by the Fridericia formula is permitted
Prolonged corrected QT (QTc) interval > 500 msec, calculated according to Fridericia's formula
Corrected QT interval (QTc) < 480 msec
Baseline QTc exceeding 450 msec (using the Bazett's formula) and/or patients receiving class 1A or class III antiarrythmic agents.
History of prolonged QTc interval.
Corrected QT interval (QTc) > 480 msec; history of QT syndrome, Brugada syndrome or known history of QTc prolongation, or torsade de pointes
QTc > 480 msec (based on the mean value of the triplicate electrocardiography [ECG]s), family or personal history of long or short QTc prolongation, or torsade de pointes (Tdp)
Every effort must be made to avoid the use of a concomitant medication that can prolong the corrected QT (QTc) interval while receiving selumetinib (hyd-sulfate AZD6244); if the patient cannot discontinue medications that prolong QTc interval while receiving selumetinib, close cardiac monitoring should be performed
Rate-corrected QT interval of electrocardiograph (QTc) > 470 msec on a 12-lead electrocardiography (ECG) during screening
Patients with prior history of QTC prolongation or QTC > 450 ms on screening ECG will be excluded
Patients with QTc interval > 450 msec.
Patients who are on treatment with drugs known to prolong the QT/QTc interval.
Corrected QT interval (QTc) using Fridericia's formula (QTcF) value > 480 msec at Screening; family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy at Screening; previous history of drug induced QTc prolongation or the need for treatment with medications known or suspected of producing prolonged QTc intervals on electrocardiogram (ECG).
Corrected QT interval (QTc) of < 480 milliseconds
Unstable cardiac dysrhythmias or persistent prolongation of the corrected QT interval (QTc) (Fridericia) to >450 msec for males or >470 msec for females.
Corrected QT interval (QTc) interval greater than 450 msec (males) or greater than 470 msec (females).
Patients must have a corrected QT (QTc) interval of less than 480 msec
Patients must not have a corrected QT interval (QTc) of > 480 msec using Bazett’s formula
Corrected QT (QTc) interval > 470 msec
Patients who have ongoing cardiac dysrhythmias, atrial fibrillation, or prolongation of corrected QTc interval to > 480 msec on 2 out of 3 electrocardiograms (EKGs) (if first EKG has QTc < 480, no need to repeat, if first EKG has QTc > 480 repeat twice for a total of 3 EKGs)
Consistent corrected QT (QTc) > 470 msec on more than one screening electrocardiography (ECG). Patients with a history of long QTc syndrome or personal or family history of ventricular arrhythmias will be excluded.
Participants must have a corrected QT (QTc) of =< 470 msec for females and =< 450 for males on the screening electrocardiogram (EKG)
Patients with QTc interval >450 msec for male and >470 msec for female.
Patients who are on treatment with drugs known to prolong the QT/QTc interval.
Has ECG abnormalities that make QT interval corrected (QTc) evaluation difficult (e.g., severe morphologic abnormalities).
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: Corrected QT (QTc) =< 480 msec
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.
Corrected QT (QTc) interval < 470 msec
Participants must have a corrected QT (QTc) of =< 470 msec on the screening electrocardiography (EKG)
Clinically significant electrocardiogram (ECG) abnormality, including a marked baseline prolonged QT/QTc ([QT interval/corrected QT interval], e.g., a repeated demonstration of a QTc interval > 500 ms)
Subjects with baseline QT prolongation > 470 msec
Subjects receiving concomitant medications that prolong corrected QT interval (QTc)
Consistent corrected QT (QTc) > 470 msec on more than one screening electrocardiograms (ECGs); patients with a history of long QTc syndrome or personal or family history of ventricular arrhythmias will be excluded
Clinically significant electrocardiogram (ECG) abnormality, including a marked baseline prolonged QT/ corrected QT (QTc) ([QT interval/corrected QT interval], eg, a repeated demonstration of a QTc interval > 500 ms)
Corrected QT (QTc) interval > 500 msec, unless a bundle branch block is also present
Corrected QT interval (QTc) =< 480 msec
Documented within 14 days of registration: Cardiac corrected QT (QTc) interval < 450 msec on electrocardiogram (EKG)
Prolonged corrected QT (QTc) interval
INCLUSION CRITERIA FOR REGISTRATION (HER2 MUTATION IDENTIFIED BY WASH U GPS LABORATORY): Corrected QT (QTc) interval =< 450 msec for men or =< 470 msec for women within 2 weeks of registration
INCLUSION CRITERIA FOR REGISTRATION (HER2 MUTATION IDENTIFIED AT AN OUTSIDE CLIA CERTIFIED LOCATION): QTc interval =< 450 msec for men or =< 470 msec for women within 2 weeks of registration
Treatment with medications that can prolong the QTc interval within the last 2 weeks
ECG with correctd QT interval (QTc) >450 msec in males or >470 msec in females at screening
Have a mean QT interval corrected for heart rate (QTc) of ?470 milliseconds on screening electrocardiogram (ECG) as calculated using the Bazett's formula at several consecutive days of assessment.
Electrocardiogram (EKG) documenting corrected QT (QTc) interval < 480 mili (m)second and no clinically significant arrhythmia
History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful. Screening corrected QT (QTc) interval > 470 msec is excluded (corrected by Fridericia). If a single QTc is > 470 milliseconds, the subject may enroll if the average QTc for the 3 ECGs is < 470 milliseconds. For subjects with an intraventricular conduction delay (QRS interval > 120 milliseconds), the JTc interval may be used in place of the QTc with sponsor approval. The JTc must be < 340 milliseconds if JTc is used in place of the QTc. Subjects with left bundle branch block are excluded. Note: QTc prolongation due to pacemaker may enroll if the JTc is normal or with medical monitor approval.
Any medications that are known to prolong the QTc interval.
Corrected QT interval (QTc) using Fridericia's formula (QTcF) value > 480 msec at Screening; family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy at Screening; previous history of drug induced QTc prolongation or the need for treatment with medications known or suspected of producing prolonged QTc intervals on electrocardiogram (ECG).
Prolonged baseline QTc
Corrected QT Interval (QTc) > 470 milliseconds (msec) on a 12-lead ECG obtained during the screening period\r\n* Note: If a machine reading is above this value, the ECG should be reviewed by a qualified reader and confirmed on a subsequent ECG
Subject has corrected QT (QTc) interval < 500 msec on baseline electrocardiogram
Patients with corrected QT (QTc) interval of > 450 msec or those on medications known to prolong QTc interval
Patients who have corrected QT (QTc) interval of > 470 msec on a screening electrocardiogram
QT interval corrected for rate (QTc) > 450 msec on the electrocardiogram (ECG) obtained at Screening
Patients with prolonged corrected QT (QTc) interval (> 450 msec) (for cohort 2a and 2b [belinostat cohorts] only, electrocardiogram [ECG] nor required for cohort 1)
Electrocardiogram (ECG) abnormalities of Q-wave infarction, unless identified 6 or more months prior to screening or QTc Fridericia (F) interval >460 msec
Baseline corrected QT (QTc) interval >= 480 milliseconds
Medications with a known risk of prolongation of QT interval
Electrocardiogram (ECG) corrected QT (QTC) < 450 msec
Have QT corrected interval of >450 milliseconds (msec) on screening electrocardiogram (ECG)
Baseline electrocardiogram (EKG) with corrected QT interval (QTc) > 470 msec (including subjects on medication); subjects with ventricular pacemaker for whom QT interval is not measurable will be eligible on a case-by-case basis
No previous history of corrected QT (QTc) prolongation as a result of medication that required discontinuation of that medication
No QTc with Bazett’s correction that is unmeasurable, or >= 480 msec on screening electrocardiogram (ECG) obtained within 7 days prior to registration for protocol therapy; if a subject has QTc >= 480 msec on screening ECG, the screen ECG may be repeated twice (at least 24 hours apart); the average QTc from the three screening ECGs must be < 480 msec in order for the subject to be eligible for the study; NOTE: co-administration of drugs that in some reports might be associated with Torsades de Pointes but at this time lack substantial evidence of Torsades de Pointes should be avoided within 2 weeks of randomization and during study; however, these drugs will be allowed, at the discretion of the investigator, if considered\r\nabsolutely necessary; in such cases, the subject must be closely monitored including regular checks of QTc and electrolytes; for patients who start on the drugs in this group while on the study treatment, the ECG must be checked within 24 hours of commencing the concomitant medication and then at least once per week while the patient remains on the medication; the frequency of ECG monitoring could revert to the standard schedule if no QTc prolongation has been noted during 4 weeks of co-administration of a drug; the electrolytes should be maintained within the normal range using supplements if necessary
Subjects with prolonged corrected QT (QTc) (> 450 msec) will be excluded from the study.
Corrected QT interval using Fridericia’s formula value > 480 msec at screening; family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy at screening; previous history of drug-induced QTc prolongation or the need for treatment with medications known or suspected of producing prolonged QTc intervals on electrocardiogram (ECG)
Corrected QT (QTc) interval ? 470 msec on screening electrocardiogram (ECG)
Corrected QT (QTc) interval using Fridericia’s formula (QTcF) >= 450 msec. Bundle branch block and prolonged QTc interval are permitted after discussion with the PI.
Ongoing cardiac dysrhythmias of National Cancer Institute (NCI) CTCAE grade >= 2 or prolongation of the corrected QT interval (QTc) interval to > 500 msec
History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful; screening corrected QT (QTc) interval > 470 milliseconds is excluded; in the event that a single QTc is > 470 milliseconds, the subject may enroll if the average QTc for the 3 ECGs is < 470 milliseconds; for subjects with an intraventricular conduction delay (QRS interval > 120 milliseconds), the corrected JT (JTc) interval may be used in place of the QTc with sponsor approval; the JTc must be < 340 milliseconds if JTc is used in place of the QTc; subjects with left bundle branch block are excluded\r\n* Note: QTc prolongation due to pacemaker may enroll if the JTc is normal
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
Participants with any history of corrected QT (QTc) prolongation (i.e. QTc interval of > 450 msec)
STRATUM A: Participants with QTc interval of > 450 msec on screening electrocardiogram (ECG)
STRATUM B: Participants with QTc interval of > 450 msec on screening ECG
STRATUM C: Participants with QTc interval of > 450 msec on screening ECG
History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful; screening corrected QT (QTc) interval >= 480 milliseconds is excluded; in the event that a single QTc is >= 480 milliseconds, the subject may enroll if the average QTc for the 3 ECGs is < 480 milliseconds; for subjects with an intraventricular conduction delay (QRS interval > 120 milliseconds), the corrected JT (JTc) interval may be used in place of the QTc with the approval of the principal investigator; the JTc must be < 340 milliseconds if JTc is used in place of the QTc; subjects with left bundle branch block are excluded; note: QTc prolongation due to pacemaker may enroll if the JTc is normal
Planned concomitant use of medications known to prolong the QT/QTc interval
Electrocardiogram (ECG) without evidence of clinically significant ventricular arrhythmias or ischemia as determined by the investigator and a rate-corrected QT interval (QTc, Bazett's formula) of < 480 msec
COHORT 3: ENDOMETRIAL CANCER: Patients with a mean corrected QT (QTc) interval of > 500 msec or receiving therapeutic agents known to prolong the QT interval
Corrected QT (QTc) < 500 msec by Fridericia
Prolonged rate corrected QT (QTc) interval ? 500 msec, calculated according to institutional guidelines
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
QTc interval using Fridericia's formula (QTcF) ?450 msec or other factors that increase the risk of QT interval prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome). Bundle branch block and prolonged QTc are permitted with approval of the study Sponsor
Corrected QT interval (QTc) prolongation > 480 msec
Corrected QT (QTc) interval =< 450 msecs
Subjects with a corrected QT (QTc) > 480 ms (QTc > 510 msec for subjects with a bundle branch block at baseline
Concomitant use of a drug with a known risk of corrected QT interval (QTc) prolongation
Baseline electrocardiogram (EKG) with corrected QT (QTc) > 470 msec (including subjects on medication); subjects with ventricular pacemaker for whom QT interval is not measurable will be eligible on a case-by-case basis at medical doctor (MD) discretion
Prolonged rate corrected QT (QTc) interval >= 500 msec, calculated according to institutional guidelines
Cardiac electrophysiologic stability as defined by an electrocardiogram (ECG) with a corrected QT (QTc) interval < 500 msec at screening
Unstable or serious concurrent medical conditions in the previous 6 months, eg, pancreatitis, severe/unstable angina, prolonged QT interval corrected by Fridericia’s formula (QTcF) > 470 msec (calculated as average of triplicate readings, taken no greater than 2 minutes apart, and no history of torsades de pointes or symptomatic corrected QT [QTc] abnormality), symptomatic congestive heart failure, myocardial infarction and/or pulmonary hypertension, ongoing maintenance therapy for life-threatening ventricular arrhythmia, stroke, and uncontrolled major seizure disorder
Unstable cardiac dysrhythmias or persistent prolongation of the corrected QT interval (QTc) (Fridericia) to >480 msec for males or >500 msec for females, based on ECG at screening (patients with stable atrial fibrillation on treatment are allowed provided they do not meet any other cardiac or prohibited drug exclusion criterion);
Patients with a corrected QT (QTc) interval of > 450 milliseconds (msec) on screening electrocardiogram (ECG) for men or > 470 msec for women
Patients with QTc interval > 480 msec or those known to have congenital long QTc syndrome.
Corrected QT (QTc) > 470 milliseconds (msec) on a 12-lead ECG obtained during the screening period; Note: If a machine reading is above this value, the ECG should be reviewed by a qualified reader and confirmed on a subsequent ECG
Family history of long QTc syndrome; personal history of long QTc syndrome or previous drug-induced QTc prolongation of at least Grade 3 (QTc >500 ms).
Known QT interval prolongation
Prolongation of corrected QT (QTc) interval to >480 milliseconds (msec) when electrolyte balance is normal
Baseline QTc exceeding 450msec (470msec for females) and / or patients receiving class 1A or class III anti-arrhythmic agents.
Electrocardiogram (ECG) - corrected QT (QTc) < 480 msec, within 2 weeks of registration (except where specified otherwise)
QTc interval of ? 450 msec (males) or 470 msec (females) calculated according to Fridericia's formula (QTc = QT/RR0.33; RR=RR interval)
A QTc interval outside of normal. (Normal: < 450 msec for males and < 460 msec for females)
Corrected QT (QTc) interval > 0.450 seconds (males) or > 0.470 seconds (females), or known history of QTc prolongation or Torsade de Pointes (TdP)
Screening rate-corrected QT interval (QTc) must be <450msec and a resting heart rate of at least 50-90 bpm via a standard 12-lead ECG within 28 days prior to registration.
Subjects with a corrected QT (QTc) > 480 ms (QTc > 510 msec for subjects with a bundle branch block at baseline)
Marked baseline prolongation of QT/corrected QT interval (QTc) interval (e.g. demonstration of a QTc interval greater than 500 milliseconds)
Baseline corrected QT Interval (QTc) > 470 milliseconds (msec) in women and > 450 msec in men; concomitant treatment with medications that prolong the QT interval and have a known risk of Torsades De Pointes is not contraindicated, but should be avoided if possible and will require more frequent electrocardiogram (EKG) monitoring
Baseline prolongation of the rate-corrected QT interval (QTc; example, repeated demonstration of QTc interval > 480 millisecond [ms], or history of congenital long QT syndrome, or torsades de pointes).
Corrected QT interval (QTc) > 480 msec on screening electrocardiogram; if QTc prolongation is felt to be related to electrolyte imbalance, an electrocardiogram (EKG) can be repeated after correction of electrolytes
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
Prolonged rate corrected QT (QTc) interval of > 500 msec, calculated according to institutional guidelines
Rate-corrected QT interval of electrocardiograph (QTc) > 470 msec on a 12-lead ECG during screening
Mean resting corrected QT interval (QTc) >470 msec
Marked baseline prolongation of QT/corrected QT (QTc) interval (QTc interval >= 500 msec) using the Fridericia method (QTc = QT/RR0.33) for QTc analysis
Baseline prolongation of QT/QTc interval (repeated demonstration of QTc ? 450 msec for men and 470 msec for women, or LVEF ? 40% by MUGA or ECHO).
Adequate cardiac function defined as\r\n* No history of congenital QTc syndrome, New York Heart Association (NYHA) class III or IV congestive heart failure (CHF)\r\n* No clinical significant cardiac arrhythmias, stroke or myocardial infarction within 6 months prior to enrollment\r\n* QTc =< 480 msec; Note: Three electrocardiograms (ECGs) must be performed for eligibility determination; if the average of these three consecutive results for corrected QT using Fridericia's formula (QTcF) is =< 480 msec, the subject meets eligibility in this regard; patients with grade 1 prolonged QTc (450-480 msec) at the time of study enrollment should have correctable causes of prolonged QTc addressed if possible (i.e. electrolytes, medications)
Baseline electrocardiogram demonstrating all of the following: corrected QT (QTc) < 450 milliseconds (msec) (men) and < 470 msec (women), PR < 240 msec, QRS < 100 msec
Electrocardiogram (EKG) corrected QT interval (QTc) < 450 msec (females)
PART 2 GROUP 1 INCLUSION CRITERIA: Corrected QTc =< 480 msec
PART 2 GROUP 2A INCLUSION CRITERIA: Corrected QTc =< 480 msec
PART 2 GROUP 3 INCLUSION CRITERIA: Corrected QTc =< 480 msec
Corrected QT (QTc) =< 450 msec. for men or QTc =< 470 msec. for women
PHASE I AND II SCLC AND UROTHELIAL CARCINOMA EXPANSION COHORT: Prolongation of QT/corrected QT (QTc) interval (QTc interval > 500 msec) using the Fridericia method of QTc analysis or family history of long QT syndrome; if single reading is above these minimum ranges, then repeat test in triplicate and evaluate eligibility based on average value
mCRPC EXPANSION COHORT: Prolongation of QT/QTc interval (QTc interval > 500 msec) using the Fridericia method of QTc analysis or family history of long QT syndrome; if single reading is above these minimum ranges, then repeat test in triplicate and evaluate eligibility based on average value
Normal electrocardiogram with corrected QT (QTc) =< 450
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
QTc prolongation >470 msec or other significant ECG abnormality noted within 14 days of treatment
Medications known to prolong corrected QT (QTC) are not allowed
Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (>= 450 msec)
Resting electrocardiogram (ECG) with corrected QT interval (QTc) > 470 msec (Fridericia’s scale)
QT interval corrected for rate (QTc) ? 480 msec on the electrocardiogram (ECG) obtained at Screening
Corrected QT (QTc) interval =/< 470 msecs, no familial history of QTc prolongation or ventricular arrhythmias
Baseline prolongation of QT/QTc interval (repeated demonstration of QTc ? 450 msec for men and 470 msec for women), or LVEF ? 40% by MUGA or ECHO.
Corrected QT interval (QTc) value > 480 msec at screening; family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy at screening; previous history of drug-induced QTc prolongation or the need for treatment with medications known or suspected of producing prolonged QTc intervals on electrocardiogram (EKG); if QTc prolongation on screening EKG is felt to be related to electrolyte imbalance, an EKG can be repeated after correction of electrolytes
QTc > 450ms, history of Qtc prolongation or predisposition for QTc prolongation or family history of sudden cardiac death or QT prolongation
Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs, using the screening clinic ECG machine-derived QTc value.
12-lead electrocardiogram (EKG) showing no active ischemia and corrected QT (QTc) interval less than 480 msec
Subject has corrected QT (QTc) interval < 500 msec on baseline electrocardiogram
QT interval corrected for rate (QTc) ? 480 msec on the electrocardiogram (ECG) obtained at Screening (average of 3 readings)
A clinically significant ECG abnormality, including a marked baseline prolonged QT or QTc interval (eg, a repeated demonstration of a QTc interval greater than 480 msec).
Corrected QT interval (QTc) =< 480 msec
Rate-corrected QT interval of electrocardiograph (QTc) > 470 msec on a 12-lead electrocardiogram (ECG) during screening
Screening electrocardiography (ECG) with corrected QT (QTc) interval > 480 milliseconds (corrected by Fridericia); in the event that a single QTc is > 480 msec, the subject may enroll if the average QTc for 3 ECGs is < 480 msec
Abnormalities on 12-lead electrocardiogram (ECG) considered by the investigator to be clinically significant (such as acute ischemia, left bundle branch block, ventricular arrhythmias) or baseline prolongation of the rate-corrected QT interval (e.g., repeated demonstration of QTc interval > 480 milliseconds)
Corrected QT(c) >= 481 ms (>= grade 2) on electrocardiogram (ECG) prior to initiation of treatment\r\n* If baseline QTc on screening ECG meets exclusion criteria:\r\n** Check potassium and magnesium serum levels\r\n** Correct any identified hypokalemia and/or hypomagnesemia and repeat ECG to confirm exclusion of patient due to QTc\r\n* For patients with HR 60-100 bpm, no manual read of QTc is required\r\n* For patients with baseline HR < 60 or > 100 bpm, manual read of QT by cardiologist is required, with Fridericia correction applied to determine QTc
Patients with prolonged corrected QT interval, defined as corrected QT (QTc) > 450 msec
Corrected QT (QTc) interval >= 480 msec (>= 500 msec for subjects with bundle branch block)
Patients with known prolonged corrected QT (QTc) syndrome or prolonged QTc syndrome noted on baseline electrocardiography (ECG)
Corrected QT interval (QTc) > 480 msecs
History of serious ventricular arrhythmia (VT or VF, ? 3 beats in a row), QTc ? 450 msec for men and 470 msec for women, or LVEF ? 40% by MUGA or ECHO.
Baseline cardiac QTc interval > 450 msecs
Baseline prolongation of the rate-corrected QT interval (QTc) (e.g. repeated demonstration of QTc interval > 480 milliseconds, or history of congenital long QT syndrome, or torsades de pointes)
History of or ongoing cardiac dysrhythmias requiring treatment, atrial fibrillation of any grade, or persistent prolongation of the QTc (Fridericia) interval to > 450 msec for males or > 470 msec for females.
Baseline electrocardiogram (EKG) with corrected QT interval (QTc) > 470 msec (including subjects on medication); subjects with ventricular pacemaker for whom QT interval is not measurable will be eligible on a case-by-case basis
Have chronic atrial fibrillation or QTc of greater than 470 msec, as calculated by Bazett's correction formula.
Screening electrocardiogram (ECG) with a corrected QT interval (QTc) > 460 msec confirmed by central laboratory prior to enrollment to the study
Corrected QT (QTc) > 480 ms (grade 2 or greater) on screening electrocardiogram (ECG)\r\n* If baseline QTc on screening ECG meets exclusion criteria on screening assessment:\r\n** Check potassium and magnesium levels\r\n** Correct any identified hypokalemia and/or hypomagnesemia and repeat ECG to confirm exclusion of patient due to QTc\r\n** For patients with a heart rate (HR) 60-100 bpm, no manual read of QT is required\r\n** For patients with baseline HR < 60 or > 100 bpm, manual read of QT by cardiologist is required using Fridericia correction
Patients with QTc > 480 msec.
Patients with the following cardiac diagnoses: ventricular tachycardia or fibrillation; Torsades de pointes; clinically significant bradycardia; sinus node dysfunction; heart block; prolonged corrected QT (QTc) interval (QTc > 450 milliseconds for males, QTc > 470 milliseconds for females); valvular, ischemic, or pulmonary heart disease; cardiomyopathy; history of heart failure
Nilotinib\r\n* Normal QTc interval on screening ECG evaluation, defined as < 450 msec for men and < 470 msec for women\r\n* Discontinuation of any medications known to contribute significantly to the risk of QT prolongation at least 48 hours prior to start of study drug; Levaquin and Zofran are an exception; of note, certain agents that prolong the corrected QT interval may be allowed but only after discussion with the chemotherapy pharmacist; should the investigator believe that therapy with a potentially QT prolonging medication is vital to an individual subject’s care, then additional ECGs should be done at the investigator’s discretion to ensure the subject’s safety
Corrected QT interval (QTc) > 480 msecs using Bazett‘s formula
Syndrome of congenital corrected QT interval (QTc) prolongation or QTc > 500 msec
Corrected QT (QTc) > 470 milliseconds (msec) on a 12-lead ECG obtained during the Screening period\r\n* Note: If a machine reading is above this value, the ECG should be reviewed by a qualified reader and confirmed on a subsequent ECG
Screening corrected QT interval (QTc) interval > 470 milliseconds
QTc interval > 450 msec
Mean resting corrected QT interval (QTc) >450 millisecond (msec), obtained from 3 ECGs recordings, using the screening clinic ECG machine-derived QTc value.
QT interval corrected for heart rate (QTc) (corrected by Fridericia's method) > 450 msec at Screening
Prolonged rate corrected QT (QTc) interval >= 500 msec, calculated according to institutional guidelines
Marked baseline prolongation of QT/corrected QC (QTc) interval (e.g. demonstration of a QTc interval greater than 500 milliseconds)
Screening ECG QTc interval 470 msec for females, 450 msec for males.
At increased risk for developing prolonged QT interval unless corrected to within normal limits prior to first dose of SNX-5422
Screening ECG QTc interval 470 msec for females, 450 msec for males.
At increased risk for developing prolonged QT interval unless corrected to within normal limits prior to first dose of SNX-5422
Screening corrected QT (QTc) interval >= 450 msec for males or >= 470 msec for females; PR interval > 250 msec for males and females within 4 weeks prior to start of any therapy
On ECG a QTc(F) interval >480 msec or any clinically significant cardiac rhythm abnormalities.
Corrected QT interval (QTc) > 480 msecs using Bazett's formula
QT intervals of QTc ? 500 msec
Corrected QT interval (QTc) prolongation > 450 milliseconds (msec)
Baseline QTc > 470 msec or previous history of QT prolongation while taking other medications
206 Baseline electrocardiogram (ECG) QTc > 470 msec.
History of non-pharmacologically induced prolonged QTc interval >480 milliseconds.
QT interval corrected for rate (QTc) > 480 msec for on the ECG obtained at Screening using Fridericia method for QTc calculation
Ongoing symptomatic cardiac dysrhythmias, uncontrolled atrial fibrillation, or prolongation of the corrected QT interval defined as > 450 msec for males and > 470 msec for female
Corrected QT (QTc) interval (Fridericia formula) > 450 msec for men or > 470 msec for women at study entry; history of congenital long QT syndrome
Corrected QT (QTc) interval =< 450 msec
Prolongation of QT interval (QT)/corrected QT interval (QTc) (QTc interval > 470 ms) using the Fridericia method of QTc analysis
Patients with prolonged corrected QT(QTc) interval defined as male > 450 msec and female > 470 msec
Patients who are on treatment with drugs known to prolong the QT/QTc interval.
Corrected QT interval (QTc) prolongation > 480 msec, as calculated by either the Bazett or Fridericia formula, as per institutional standard
Corrected QT (QTC) by 12 lead electrocardiography (EKG) < 450 msecs
Corrected QT (QTc) interval > 470 msec (females) or > 450 msec (males)
Obtained =< 7 days prior to registration: Corrected QT (QTc) interval =< 500 msec on the baseline electrocardiogram
Corrected QT (QTc) interval =< 480 milliseconds
Corrected QT (QTc) interval > 480 msec on baseline electrocardiogram (EKG)
Documented history of prolonged QTc interval =< 6 months prior to registration
Electrocardiogram (ECG) corrected QT (QTc) =< 450 msec
Corrected QT interval (QTc) =< 470 msec (based on average of screening triplicates)
Clinically significant active cardiovascular disease or history of prolonged QT interval corrected for heart rate (QTc)
Subjects must have normal corrected QT interval (QTc) =< 470 msec (based on average of screening triplicates)
Corrected QT (QTc) interval > 450 ms on screening 12-lead electrocardiogram (ECG)\r\n* If baseline QTc on screening ECG meets exclusion criteria:\r\n** Check calcium, potassium, and magnesium serum levels\r\n** Correct any identified hypocalcemia, hypokalemia, and/or hypomagnesemia and repeat ECG to confirm exclusion of patient due to prolonged QTc interval\r\n* For patients with heart rate (HR) 60-100 beats per minute (bpm), manual read of QTc is not required\r\n* For patients with a baseline HR < 60 bpm or > 100 bpm, manual read of the QT interval by a cardiologist is required, with Fridericia correction applied to determine QTc (ie, QTcF)
QTc interval >460 msec (males) or >470 msec (females); or repeated demonstration of a QTc interval >450 msec.
The use of concomitant medications that prolong the QT/QTc interval.
Corrected QT (using Bazett's formula [QTcB]) interval < 500 msecs
Patients with mean QTc interval >450 msec at screening and patients taking drugs known to prolong the QTc interval (see Section 9, Appendix D) who cannot be switched to an alternative drug
Baseline corrected QT (QTc) interval > 500 msec
Subjects with baseline QTc interval >470 msec at screening
Inability to measure QT interval on ECG
Corrected QT interval (QTc) =< 480 msec per Fridericia’s formula AND PR interval =< 200 msec (using 12-lead electrocardiography [EKG])
Corrected QT interval less than 500 milliseconds by electrocardiogram (EKG)
Corrected QT (QTc) =< 480 msec\r\n* Note: patients with grade 1 prolonged QTc (450-480 msec) at the time of study enrollment should have correctable causes of prolonged QTc addressed if possible (i.e. electrolytes, medications)
Corrected QT (QTc) interval on electrocardiogram must be =< 480 msec (Fridericia correction)
Prolonged corrected QT interval (QTc) on pre-entry electrocardiogram (> 470 msec for men and > 480 msec for women per American Heart Association (AHA)/American College of Cardiology (ACC) 2011 scientific statement
Marked baseline prolongation of QT/QT corrected (QTc) interval (e.g. demonstration of a QTc interval greater than 500 milliseconds)
Patients with a history of prolonged corrected QT (QTc) syndrome
Patients with a known history of a prolonged QT interval (corrected QT interval [QTc] > 480) may not be enrolled in this study
Corrected QT interval (QTc) =< 480 msec
Corrected QT interval (QTc) >= 480 msec and/or receiving any concomitant medications that are associated with a risk of QTc prolongation and/or torsades de pointes; NOTE: these medications should be discontinued or replaced with drugs that do not carry these risks
Patients with corrected QT interval (QTc) prolongation greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 (> 480 msec); in addition, patients should not be receiving non-study medications known to prolong QTc
Concomitant medication(s) known to increase the QT interval
Documentation of the patient’s history of corrected QT interval (QTc) prolongation, family history of prolonged QTc, and relevant cardiac disease within 10 days prior to registration
QTc prolongation defined as a QTc interval >= 480 msecs or other significant electrocardiogram (EKG) abnormalities are ineligible; Note: if unsure about EKG abnormality, the treating physician should discuss this with Drs. Sherman or Bible
Patients must have corrected QT (QTc) interval < 500 msec on baseline electrocardiogram (EKG)
Patient must have an electrocardiogram (ECG) performed within 42 days prior to registration; patient must not have mean corrected QT (QTc) > 500 msec (with Bazett’s correction) in screening electrocardiogram, or other significant ECG abnormality, New York Heart Association (NYHA) classification III or IV; patient must not require concurrent use of drugs or biologics with proarrhythmic potential
Prolonged corrected QT interval (QTC) on electrocardiogram (EKG)
Prolonged QTC
Corrected QT interval (QTc) =< 480 msec
Has clinically active heart disease including prolonged corrected QT interval
Patient must have a corrected QT interval (QTc) interval < 461 msec on the 12 lead electrocardiogram (ECG) within 42 days prior to registration, patients with asymptomatic or incidental bundle branch blocks may have QTc measured by a cardiologist or standard formulas such as Bazett’s or Fridericia’s to adjust for pre-existing blocks
QTc > 470 msec (including subjects on medication);
Heart-rate corrected QT interval (QTc) prolongation > 470 msec at screening
Corrected QT interval (QTc) > 480 milliseconds as corrected by the Fridericia formula
QTc interval >0.450 seconds (males) or >0.470 (females), or known history of QTc prolongation or Torsade de Pointes (TdP)
Corrected QT interval (QTc) > 480 miliseconds (msecs)
Patients with baseline QTc > 480 msec.
QTc >480 msec
Has marked prolongation of QTc(F) interval at screening or baseline (QTc[F] interval > 470 msec) using the Fridericia method of correction for heart rate.
A clinically significant electrocardiogram (ECG) abnormality, including a marked Baseline prolonged QT/QTc interval (e.g., a repeated demonstration of a QTc interval >500 milliseconds (msec)).
History of prolonged QTc interval (e.g., repeated demonstration of a QTc interval > 450 milliseconds).
Cardiac function: baseline corrected QT (QTc) interval =< 450 msecs
Baseline cardiac QTc interval > 450 msecs
Has QT interval corrected for heart rate (QTc) ?480 msec.
Has marked prolongation of QTc(F) interval at screening or baseline (QTc[F] interval > 470 msec) using the Fridericia method of correction for heart rate
Corrected QT interval duration prolongation
No marked baseline prolongation of QT/QTc interval
Have chronic atrial fibrillation or QTc interval corrected for heart rate of greater than 470 msec in adults and 450 msec in pediatrics (< 18 years).
Patients with prolonged corrected QT (QTc) interval (> 500 msec) determined by electrocardiogram (EKG) within 28 days prior to registration
Baseline prolongation of the rate-corrected QT interval (QTc; example, repeated demonstration of QTc interval >480 millisecond [ms], or history of congenital, long-QT syndrome, or torsades de pointes).
Have a corrected QT interval >470 milliseconds as calculated be the Fredericia equation.
A clinically significant electrocardiogram (ECG) abnormality (ie, corrected QT interval [QTc] interval greater than 480 msec when electrolyte balance is normal), or a history of risk factors for torsade de pointes, hypokalemia, long QT syndrome, or the use of concomitant medications resulting in a prolongation of QTc interval.
Mean QT interval corrected for heart rate (corrected QT [QTc]) < 470 msec calculated from 3 electrocardiograms (ECGs) performed at least 2 minutes apart using Fridericia’s correction
Patients with a left ventricular cardiac ejection fraction < 50% as assessed by an echocardiogram or MUGA scan or prolonged QTc interval of Grade 2 or higher or history of prolonged QTc interval from other drugs.
Mean resting corrected QT interval (QTc) ?450 msec for males and ?470 msec for females.
Known history or predisposition to QT interval prolongation
Prolongation of QT/QTc interval
Electrocardiogram (ECG) demonstrating clinically significant arrhythmias (Note: participants with chronic atrial arrhythmia, ie, atrial fibrillation or paroxysmal supraventricular tachycardia, are eligible). A clinically significant ECG abnormality, including a marked prolonged QT/QTc interval (eg, a repeated demonstration of a QTc interval of greater than 500 ms).
Patients must have corrected QT (QTc) =< 500 msec
Corrected QT interval (QTc) > 470 msec; excluded are patients who may develop prolongation of QTc; these conditions include patients with hypokalemia or hypomagnesemia, patients with congenital long QT syndrome, patients taking anti-arrhythmic medicines or other medicinal products that lead to QT prolongation, and cumulative high-dose anthracycline therapy
Corrected QT interval (QTc) < 480 msec
Corrected QT (QTc) interval > 500 msec; if QTc interval is > 500 msec, then 2 additional electrocardiograms (ECGs) should be obtained over a brief period of time (e.g., within 15-20 minutes) to confirm the abnormality; the average QTc interval will be determined from the 3 ECG tracings by manual evaluation and will be used to determine if the subject will be excluded from the study; the same method of QTc determination must be used throughout the subject’s participation in the trial
Parts A, B, C, and E: Have QTc interval of > 470 millisecond (msec) on screening electrocardiogram (ECG). Part D participants have QTc interval of >450msec on screening ECG. Additional Exclusion Criteria For Part C
Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (> 450 msec) within 30 days prior to study registration
Corrected QTc interval > 480 msec; baseline electrocardiogram (EKG) obtained pre-transplant does not need to be repeated unless clinically indicated
Treatment with medications known to cause corrected QT (QTc) interval prolongation within 7 days of study day 1 is not permitted unless approved by the sponsor; use of ondansetron is permitted for treatment of nausea and vomiting
Patients with a baseline QTc > 500 msec and patients with a family history of prolonged QT syndrome
Clinically significant electrocardiogram (ECG) abnormality, including a marked baseline prolonged QT/corrected QT (QTc) ([QT interval/corrected QT interval], e.g., a repeated demonstration of a QTc interval > 480 ms), a family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or torsade de pointes (TdP)
Concurrent use of digoxin due to cardiac disease; corrected QT (QTc) interval >= 450 milliseconds in men and >= 470 milliseconds in women within 2 weeks of registration or known history of QTc prolongation or Torsades de Pointes
QTc <450 msec on screening ECG.
Corrected QT interval using Fridericia’s formula (QTcF) value > 480 msec at screening; family or personal history of long corrected QT (QTc) syndrome or ventricular arrhythmias including ventricular bigeminy at screening; previous history of drug-induced QTc prolongation or the need for treatment with medications known or suspected of producing prolonged QTc intervals on electrocardiogram (ECG)
Corrected QT interval (QTc) > 470 milliseconds (msec) on a 12-lead electrocardiography (EKG) obtained during the screening period; if a machine reading is above this value, the EKG should be reviewed by a qualified reader and confirmed on a subsequent EKG
QTc interval ? 470 msec at Baseline
Abnormalities on 12-lead electrocardiogram (ECG) considered by the investigator to be clinically significant or baseline prolongation of the rate-corrected QT interval (e.g., repeated demonstration of QTc interval > 480 milliseconds).
Patient must have a corrected QT (QTc) interval on electrocardiogram (ECG) =< 0.48 seconds by Bazett’s calculation at screening
Corrected QT interval (QTc)/QT Fridericia equation (QTf) interval >= 480 milliseconds; unless secondary to pacemaker or bundle branch block
Patients taking drugs that can cause 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)
Patient requires the use of concomitant medications that are contraindicated with cardiac glycosides and/or are known to prolong the QT/QTc interval during study participation (see Appendix 2).
QT interval corrected (QTc) <450 millisecond (msec) or QTc <480 msec for patients with bundle branch block.
The QTc is the QT interval corrected for heart rate according to either Bazett's formula (QTcB)
For purposes of this data analysis, Bazett's formula will be used as the primary method of calculating the corrected QT interval. The QTc should be based on either a single Electrocardiogram (ECG) or an average of 3 sequential ECGs obtained within 24 hours of each other.
Concurrent treatment with any agent known to prolong the corrected QT (QTc) interval
Mean resting correct QT interval (QTc) >470 msec obtained from triplicate electrocardiagrams
Subjects with heart-rate corrected QT (QTc) interval ? 450 msec or with other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome). Subjects with right bundle branch block and a prolonged QTc interval should be reviewed by the Medical Monitor for potential inclusion.
Screening ECG QTc interval ?470 msec for females, ?450 msec for males.
Grade 3 corrected QT interval (QTc) prolongation (QTc > 500 msec on two separate electrocardiograms (ECGs)
Patients must have QTc interval less than 450 msec
Patients must have a baseline electrocardiogram (ECG) showing corrected QT (QTc) interval =< 460 msec within 28 days prior to registration
Corrected QT interval (QTc) > 480 msec; history of QT syndrome, Brugada syndrome or known history of QTc prolongation, or torsade de pointes
Participants with a history of congenitally prolonged corrected QT interval (QTc), a first degree relative with unexplained sudden death under 40 years of age, or a measured QTcB (Bazett’s correction) longer than 480 msec on electrocardiogram (ECG); ECGs should be performed after correction of electrolyte abnormalities; participants with a prolonged QTcB should have a repeat ECG twice, at least 24 hour apart, and the average of the 3 QTcBs should not exceed 480 msec; history of QT prolongation associated with other medications that required discontinuation of that medication
Subjects with a corrected QT interval (QTc) > 480 msec (QTc > 510 msec for subjects with bundle branch block) at baseline
Normal corrected QT (QTc) interval defined on electrocardiogram (EKG) as QTc =< 440 msec\r\n* Note: patients who are assigned to arm B must have QTc =< 440 msec on day (D)1 and D8 of cycle 1 of eribulin treatments for continued eligibility\r\nPostmenopausal women defined as women with:\r\n* Prior bilateral surgical oophorectomy, or\r\n* Medically confirmed post-menopausal status defined as spontaneous cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause
Current use of drugs known to prolong the QTc interval including class Ia and III antiarrhythmics or history of congenital long QTc syndrome
Corrected QT interval using Fridericia's formula (QTcF) value > 480 msec at screening; family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy; previous history of drug-induced QTc prolongation or the need for treatment with medications known or suspected of producing prolonged QTc intervals on electrocardiogram (ECG)
Mean resting QTc >470 msec obtained from 3 ECGs
Corrected QT interval (QTc) > 480 msecs using Bazett's formula; electrocardiography (EKG) for screening must be =< 28 days before registration
Subject has Long corrected QT interval (QTc) Syndrome at Screening.
On electrocardiogram, corrected QT (QTc) interval > 500 msec
Prolonged rate corrected QT (QTc) interval >= 500 msec, calculated according to institutional guidelines
Planned concomitant use of medications known to prolong the QT/QTc interval
Participant has a corrected QT (QTc) interval > 470 ms or known history of QTc prolongation or Torsade de Pointes
Patients must not have a corrected QT (QTc) interval >= 480 msecs within 28 days prior to registration
Subjects with a QTc > 480 msec (QTc > 510 msec for subjects with Bundle Branch Block) at baseline
Corrected QT interval (QTc) of > 480 msec using Bazett’s formula
Corrected QT (QTc) prolongation, as defined by > 470 milliseconds on ECG
No ongoing cardiac dysrhythmias, atrial fibrillation, or prolongation of corrected QT (QTc) interval to > 480 msec
QTc\t=< 480 msecs
Corrected QT interval (QTc) > 480 msecs\r\n* Note: correction method should be reported
Prolongation of corrected QT interval (QTc) > 480 milliseconds using Bazett’s formula
Prolonged QTc interval on pre-entry electrocardiogram (>/= 450 msec)
Prolonged corrected QT (QTc) interval (>= 500 msec), as calculated by Bazett's formula
Corrected QT (QTc) interval greater than or equal to 480 msecs (>= 500 msec for subjects with bundle branch block)
Corrected QT interval (QTc) < 480 msecs
Electrocardiogram (ECG) without evidence of clinically significant ventricular arrhythmias or ischemia as determined by the investigator and a rate-corrected QT interval (QTc, Bazett's formula) of < 480 msec
Inability to determine the QT interval on ECG
Corrected QT (QTc) interval > 500 msec, unless a bundle branch block is also present
Patient with corrected QT (QTc) interval must be less than 500 msec
Patients must have corrected QT (QTc) < 500 msec
Patients with QTc prolongation (defined as a QTc interval equal to or greater than 500 msec) or other significant echocardiogram (ECG) abnormalities are excluded
Corrected QT interval (QTc) > 480 msecs using Bazett’s formula
Corrected QT interval (QTc) > 475 milliseconds
QTcF > 480 msec, family or personal history of long QTc syndrome or ventricular bigeminy; previous history of drug-induced QTc prolongation or the need for medications known or suspected of producing prolonged QTc intervals on ECG
Corrected QTc > 470 msec; the corrected QTc may be corrected using either Bazett’s or Fridericia’s formula; in general Fridericia corrected QT interval (QTcf) is the preferred correction method
Corrected QT interval (QTc) > 480 msecs using Bazett’s formula
Corrected QT (QTc) interval > 470 msec
Corrected QT interval less than 500 milliseconds by electrocardiogram (EKG)
Prolongation of corrected QT interval (QTc) > 480 msecs
The subject has a baseline corrected QT interval < 500 within 28 days before randomization
Subjects with a baseline corrected QT (QTc) of equal to or greater than 480 msecs or other significant electrocardiogram (ECG) abnormalities
Corrected QT interval (QTc) > 480 msecs using Bazett’s formula
Prolongation of corrected QT interval (QTc) > 480 msecs
Inability to monitor the QT interval on electrocardiogram (ECG)
Corrected QT interval (QTc) (based on Bazett) > 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
Corrected QT (QTc) =< 500 msec on baseline electrocardiogram (ECG)
Bazett-corrected QT (QTcB) interval ?501 msec at the time of transition to this study
Baseline corrected QT (QTc) > 480 msec or other clinically significant baseline electrocardiogram (ECG) abnormality
At eltrombopag dose levels 200 mg and above cohorts, subjects with a corrected QT (QTc) > 480 msec at screening, if other drugs known to cause prolonged QT are stopped an electrocardiogram (EKG) documenting QTc below 480 msec is required
Corrected QT (QTc) interval >/= 480 msec at the time of transition to this study
Prolongation of corrected QT interval (QTc) > 480 msecs
EXPANSION COHORT ONLY: Prolongation of corrected QT interval (QTc) > 480 msecs
QTc > 450 msec
Treatment with medications known to cause corrected QT (QTc) interval prolongation within 7 days of study day 1 is not permitted unless approved by the sponsor; use of ondansetron is permitted for treatment of nausea and vomiting
QTc > 470 msec on electrocardiogram
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 of the following:\r\n* History of myocardial infarction within six months\r\n* Patients with corrected QT (QTc) prolongation > 500 msec or other significant electrocardiogram (ECG) abnormality noted within 14 days of treatment\r\n** For patients enrolled in the Phase 1-T portion of the protocol, the QTc should not exceed 470 msec\r\n* New York Heart Association (NYHA) classification of III or IV\r\n* If cardiac function assessment is clinically indicated or performed: left ventricular ejection fraction (LVEF) less than normal per institutional guidelines, or < 55%, if threshold for normal not otherwise specified by institutional guidelines\r\n* Condition requiring concurrent use of drugs or biologics with pro-arrhythmic potential
Mean QTc >= 450 msec (for males) or QTc >= 470 msec (for females)
Corrected QT interval (QTc) must be < 500 msec
Prolonged QTc interval on pre-entry electrocardiogram (> 470 msec)
QTc interval >0.45 seconds
Patients must not have any clinically significant cardiovascular disease including the following: myocardial infarction or ventricular tachyarrhythmia within 6 months, prolonged corrected QT interval (QTc) > 480 msec (Fridericia correction), ejection fraction less than institutional normal, major conduction abnormality (unless a cardiac pacemaker is present); patients with any cardiopulmonary symptoms of unknown cause (e.g. shortness of breath, chest pain, etc.) are to be evaluated by a baseline echocardiogram with or without stress test as needed in addition to electrocardiogram (EKG) to rule out QTc prolongation; the patient may be referred to a cardiologist at the discretion of the principal investigator; patients with underlying cardiopulmonary dysfunction are excluded from the study
Patients must not have QTc prolongation defined as a QTc interval equal to or greater than 450 milliseconds (msecs)
Has electrocardiogram (ECG) abnormalities that make QT interval corrected (QTc) evaluation difficult.
the potential to prolong the QT interval, or
Inability to measure QT interval on ECG
Baseline prolongation of QT/corrected QT (QTc) interval, i.e., defined as an average QTc interval > 450 msec calculated using the Fridericia formula for QT correction; long QT syndrome; or the required use of concomitant medication that may cause torsade de pointes
Grade >= 2 QT interval corrected (QTc) prolongation on screening electrocardiogram (ECG) within 28 days of enrollment, or history of ventricular arrhythmia
Appropriately corrected screening ECG QTc interval 470 msec for females, 450 msec for males.
Currently receiving medications known to cause QT prolongation AND corrected QTc of 450 msec for females, 430 msec for males.
QT/QTc interval >480 msec, before C1D1 treatment administration, as determined by screening electrocardiogram (ECG)
Subject is taking medication known to prolong the QT interval.
QT/QTc interval > 450 msec, as determined by screening ECG performed no earlier than 1 week before C1D1
Corrected QT (QTc) interval >= 450 ms (ie, grade 1 or higher) on electrocardiogram (ECG) prior to initiation of study treatment\r\n* If baseline QTc on screening ECG is >= 450 ms (ie, grade 1 or higher):\r\n** Check potassium and magnesium serum levels\r\n** Correct any identified hypokalemia and/or hypomagnesemia and repeat ECG to confirm QTc interval\r\n* For patients with baseline heart rate (HR) < 60 beats per minute (bpm) or > 100 bpm, manual measurement of QT interval by cardiologist is required, with Fridericia correction applied to that manual measurement to determine the QTc for eligibility consideration\r\n* Note: For patients with HR 60-100 bpm, manual measurement of QTc interval and use of Fridericia calculation is NOT required
Concurrent administration of crizotinib and agents that can cause corrected QT (QTc) prolongation is not permitted
Participants with electrocardiogram (ECG) abnormalities considered by the investigator to be clinically significant, or repeated baseline prolongation of the rate-corrected QT interval (QTc).
Participants with electrocardiogram (ECG) abnormalities considered by the investigator to be clinically significant, or repeated baseline prolongation of the rate-corrected QT interval (QTc).
Cardiac function: 12-lead electrocardiogram (ECG) with normal tracing, or non-clinically significant changes that do not require medical intervention; corrected QT (QTc) interval is to be < 470 msec
Corrected QT interval (QTc) > 470 msec on electrocardiogram (by Bazett’s; average of triplicate recordings at the discretion of the principal investigator [PI]) will exclude patients from entry on study; medications that are known to cause QTc interval prolongation are prohibited for patients entering on trial; patients for whom a given medication that may cause QTc interval prolongation cannot be discontinued, may be eligible at the discretion of the study PI, provided QTc interval criteria is met at enrollment
Subjects with a corrected QT interval (QTc) <450 milliseconds (msec) or <480msec for subjects with bundle branch block. The QTc is the QT interval corrected for heart rate according to Fridericia's formula (QTcF), machine or manual overread. For subject eligibility and withdrawal, QTcF will be used. For purposes of data analysis, QTcF will be used. The QTc should be based on single or averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief recording period
Has marked prolongation of QTc interval at screening or baseline using the Fridericia method of correction for heart rate
Participants with mean corrected QTc interval > 500 msec, as assessed within 4 weeks prior to enrollment, or participants who require medication known to prolong the QT interval
Corrected QT interval (QTc) > 480 msecs using Bazett’s formula
Corrected QT interval (QTc) prolongation (defined as a QTc interval > 480 msec) or other significant electrocardiogram (ECG) abnormalities
Corrected QT interval (QTc) > 480 msecs using Bazett's formula.
Patients with corrected QT (QTc) prolongation (defined as a QTc interval equal to or greater than 500 msec) or other significant electrocardiogram (ECG) abnormalities are excluded
Corrected QT (QTc) (Frederica) prolongation > 470 msec
Corrected QT (QTc) interval =< 470 msec
Clinically significant electrocardiogram (ECG) abnormality, including a marked Baseline prolonged QT interval/corrected QT interval ([QT/QTc], example, a repeated demonstration of a QTc interval >500 millisecond [ms]).
Consistent corrected QT (QTc) > 450 msec for men and > 470 msec for women by Fridericia formula, on 3 separate electrocardiograms (ECGs); patients with a history of long QTc syndrome or personal or family history of ventricular arrhythmias will be excluded
Screening electrocardiogram (EKG) with a corrected QT (QTc) > 450 msec
Patients with significant cardiovascular disease (New York Heart Association class III or IV cardiac disease), symptomatic congestive heart failure, myocardial infarction within the past 6 months, unstable angina, unstable arrhythmia or a need for anti-arrhythmic therapy (use of frequency adjusting medication for atrial fibrillation is allowed, if stable medication for at least last month prior to initiation of belinostat treatment and medication not listed as causing Torsades de Pointes), or evidence of acute ischemia on electrocardiogram (ECG); marked baseline prolongation of QT/corrected QT (QTc) interval, e.g., repeated demonstration of a QTc interval > 450 msec; long QT syndrome; concomitant use of drugs known to prolong the QT interval and/or cause Torsades de Pointes is not allowed during the study or within 2 weeks of study entry; these drugs should also be avoided for up to 4 weeks following discontinuation of study treatment; drugs that may be associated with Torsades de Pointes but lack substantial evidence will be allowed at the discretion of the PI (although it is preferable to substitute an alternate medication), and patients will be closely monitored
Have corrected QT (QTc) interval of >470 milliseconds on screening electrocardiogram (ECG).
Patients with current evidence of significant cardiovascular disease (New York Heart Association class III or IV cardiac disease), symptomatic congestive heart failure, dilated/hypertrophic or restrictive cardiomyopathy, myocardial infarction (within the past 6 months), unstable angina, unstable arrhythmia or a need for anti-arrhythmic therapy (use of medications for rate control for atrial fibrillation is allowed such as calcium channel blockers and beta-blockers, if stable medication for at least last month prior to initiation of MK-2206 treatment and medication not listed as causing torsades de pointes), or evidence of acute ischemia on electrocardiogram (ECG); marked baseline prolongation of QT/QTc interval, e.g., repeated demonstration of a QTc interval > 450 msec*; long QT syndrome; the required use of concomitant medication that may cause torsades de pointes or may cause a significant prolongation of the QTc\r\n*Note: Due to difficulties assessing QTc in patients with heart block, they may be eligible if deemed safe by a cardiologist
Screening ECG with a QTc > 450 msec.
Corrected QT interval (QTc) using Fridericia's formula value > 480 msec at screening; family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy at screening; previous history of drug induced QTc prolongation or the need for treatment with medications known or suspected of producing prolonged QTc intervals on electrocardiogram (ECG).
Inability to measure QT interval on ECG
Heart-rate corrected QT (QTc) interval >450 msec or with other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome). Subjects with right bundle branch block and a prolonged QTc interval should be reviewed by the Medical Monitor for potential inclusion
Patients taking medications known to prolong the QTc interval directly or that interact pharmacodynamically with medicines to prolong the QTc interval.
Must not have QT interval of >470 millisecond.
Corrected QT interval (QTc) > 500 milliseconds in a 12-lead electrocardiogram (ECG) during screening.
Clinically active heart disease including prolonged QTc or prolonged PR interval, or history of arrhythmias
Corrected QT interval (QTc) > 480 msec
Prolonged rate corrected QT interval (QTc) >=500 millisecond (msec), calculated according to institutional guidelines.
Patients with a baseline QT/corrected QT (QTc) interval >= 501 msec
Baseline corrected QT interval (QTc) > 470 msec (average of triplicate electrocardiogram [ECG] recordings); a consistent method of QTc calculation must be used for each patient's QTc measurements; QTcF (Fridericia's formula) is preferred
Baseline QTc >470 msec and/or previous history of QT prolongation while taking other medications.
Baseline ATc>470 msec and/or previous history of QT prolongation.
Corrected QT (QTc) interval using Bazett's Formula; (QTcB) >= 480 msecs
Important abnormalities of the ECG that may interfere with the interpretation of QTc interval changes at screening
QTc (corrected QT) interval < 480 msec.
Patients must have an electrocardiogram (EKG) documenting normal intervals (especially QTc interval < 480 msec) and no arrhythmia prior to enrollment
Mean QTc interval >= 480 msec at screening
Mean corrected QT (QTc) interval >= 450 (triplicate electrocardiograms [ECGs]) or history congenital prolonged QT interval
Corrected QT (QTc) interval >= 500 milliseconds
Baseline QTc exceeding 450 msec (470 msec for females) using the Bazetts formula and/or patients receiving class 1A or class III antiarrythmic agents.
Corrected QT (QTc) interval > 450 msec (males) or > 470 msec (females)
QTc interval <= 300 msec
Screening ECG QTc interval ? 470 msec for females, ? 450 msec for males.
Subjects with a QT interval corrected for heart rate according to Bazett's formula (QTcB) <450millisecond (msec) or <480msec for subjects with bundle branch block. The QTc should be based on single or averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief recording period.
Corrected QT interval (QTc) of greater than 500 msec
Because of the potential risk of corrected QT (QTc) changes, serum potassium levels must be within institutional normal limits
Electrocardiogram (EKG) abnormalities of:\r\n* Q-wave infarction, unless identified 6 or more months prior to screening\r\n* QTc interval > 470 msec, the upper limit of normal for women
Patients must not have prolonged corrected QT (QTc) interval (> 500 msec) determined by electrocardiogram (EKG) within 28 days prior to registration
QT/QTc interval >450 msec, as determined by screening electrocardiogram (ECG)
Concomitant medication that may cause Torsade de Pointes, i.e. prolongation of the QT interval > 500 msec
Patients may not have any clinically significant cardiovascular disease including the following:\r\n* Myocardial infarction or ventricular tachyarrhythmia within 6 months\r\n* Prolonged corrected QT interval (QTc) > 480 msec\r\n* Ejection fraction less than 50%\r\n* Major conduction abnormality (unless a cardiac pacemaker is present)
Have chronic atrial fibrillation or QTc interval corrected for heart rate of greater than 470 msec.
Patient must have a QT/QTc interval ? 450 msec.
Patient with prolonged QT/QTc (defined as QTc interval > 450 msec) are not eligible.
Corrected QT interval (QTc) < 480 msec (with Bazett’s correction) in screening electrocardiogram
Corrected QT (QTc) interval > 500 msec (Bazett formula or Fridericia formula based on institutional standard)
Electrocardiogram (EKG) with mean corrected QT (QTc) interval < 450 msec
Corrected QT (QTc) interval > 500 msec on baseline electrocardiogram (EKG)
Documented history of prolonged QTc interval =< 6 months prior to registration
Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec) on the Bazett’s correction
Baseline QTc > 470 msec or previous history of QT prolongation while taking other medications
Grade > 1 QTc prolongation at baseline (> 450 msec by Bazett formula) confirmed by a repeat electrocardiogram (ECG)
Corrected QT interval > 480 msecs using Bazett's formula.
Subjects with a high probability of Long QT Syndrome or QTc interval prolongation of more than or equal to 501 msec on at least two separate ECGs, following correction of any electrolyte imbalance.
Patient has a QTcF value of >480 msec; family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy; previous history of drug-induced QTc prolongation
Corrected QT (QTc) interval > 500 msec
QTc greater than 470 msec.
Have a QTc interval greater than 470 msec
Corrected QT (QTc) prolongation with other medications; if the medication can be discontinued and an alternative medication started that does not cause QTc prolongation, the patient would be eligible; if no alternative medication is available and the medication cannot be discontinued for medical reasons, then the patient would not be eligible
QTc with Fridericia’s correction that is not measurable, or >= 480 msec on screening electrocardiogram (ECG); (Note: if a patient has a QTc interval >= 480 msec on screening ECG, the screen ECG may be repeated twice [at least 24 hours apart]; the average QTc from the three screening ECGs must be < 480 msec in order for the patient to be eligible for the study); patients who are receiving a drug that has a risk of QTc prolongation are excluded if QTc is >= 460 msec
Have QTc interval of >500 msec on screening electrocardiogram
Prolongation of corrected QT interval (QTc) > 480 milliseconds (msec)
Corrected QT interval (QTc) ? 450 msec at least 7 days prior to registration for protocol therapy.
Patients must not have a marked baseline prolongation of QT/corrected QT (QTc) interval (e.g., demonstration of a QTc interval > 500 milliseconds (ms)
QTc prolongation defined as a QTc greater than or equal to 470 ms or a prior history of cardiovascular disease, arrhythmias, or significant ECG abnormalities
Must have electrocardiogram (EKG) with corrected QT (QTc) interval < 450 msec and Echocardiogram with shortening fraction >= 27% or ejection fraction > 50%
Patients with marked baseline prolongation of QT/corrected QT (QTc) interval (QTc interval > 450 msec for males or > 470 msec for females) using the Fridericia method for QTc analysis
Corrected QT interval (QTc) > 470 milliseconds on baseline electrocardiogram (ECG) (using corrected QT interval using Fridericia [QTcF] or Bazett [QTcB]); if electrolytes are abnormal, they may be corrected and baseline ECG should be repeated
Cardiovascular disease, including recent history of or currently clinically symptomatic and uncontrolled congestive heart failure, arrhythmia, angina, corrected QT (QTc) prolongation or other QTc risk factors, myocardial infarction; patients with Common Terminology Criteria for Adverse Events (CTCAE) grade 2 cardiac arrhythmias may be considered for inclusion if the arrhythmias are stable, asymptomatic, and unlikely to affect patient safety; patients will be excluded if they have ongoing cardiac dysrhythmias of CTCAE grade >= 3, corrected QT interval (QTc) prolongation > 450 ms, or other factors that increase the risk for QT interval prolongation (e.g., heart failure, hypokalemia [defined as serum potassium < 3.0 mEq/L that is persistent and refractory to correction], or family history of long QT interval syndrome)
Corrected QT interval (QTc) > 480 msecs
Corrected QT interval (QTc) > 480 msecs (record QTc correction method)
Patients may not currently be taking quinidine, ceritinib, highest risk corrected QT interval (QTc)-prolonging agents, mifepristone, or succinylcholine
Patients must have electrocardiogram with corrected QT (QTc) with correction within 28 days prior to registration
Baseline QTc ?470 msec and no previous history of QT prolongation while taking other medications.
Clinically significant electrocardiogram (ECG) abnormality, including a marked baseline prolonged QT/QTc ([QT interval/corrected QT interval], e.g., a repeated demonstration of a QTc interval > 500 ms)
EXCLUSION CRITERIA FOR CROSSOVER THERAPY: Clinically significant electrocardiogram (ECG) abnormality, including a marked baseline prolonged QT/QTc ([QT interval/corrected QT interval], e.g., a repeated demonstration of a QTc interval > 500 ms)
Corrected QT interval (QTc) =< 480 msec
Medical disorder that would endanger subject’s well-being (e.g., uncorrected hypothyroidism, cardiac arrhythmia, hypertension requiring treatment, sick sinus syndrome, prolonged corrected QT [QTc])
Current evidence of cardiac arrhythmias defined as corrected QD interval (QTc) >= 480 mm/sec
Patients with a known or screening-period-determined corrected QT (QTc) interval > 450 msec and patients who require a therapy with a drug known to prolong the QT/QTc interval, are ineligible
Diagnosis of narcolepsy, sick sinus syndrome, arrhythmia, or prolonged corrected QT interval (QTc)
Patients with a known pathologic prolongation of the corrected QT (QTc)
Corrected QT (QTc) interval within normal range for age
QTc interval < 480 milliseconds (msec) on the baseline electrocardiogram.
Corrected QT interval (QTc) =< 480 msec
Has an 12-lead ECG obtained at screening visit which shows medically significant abnormality(ies) (e.g. left bundle branch block, frequent premature ventricular contractions, QTc interval prolongation > 450 msec for males and > 470 msec for females)
Subjects having an electrocardiogram with a prolonged corrected QT (QTc) interval by manual reading: QTc greater than 490 msec
Corrected QT interval (QTc) > 450 msec (male) or > 470 msec (female) on 12-lead electrocardiogram
Screening ECG with a QTc > 450 msec. If QTc > 450 and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient rescreened for QTc.
Marked baseline prolongation of QT/corrected QT (QTc) interval (e.g. demonstration of a QTc interval greater than 500 milliseconds)
Previous history of Corrected QT Interval (QTc ) prolongation resulting from medication that required discontinuation of that medication
QTc with Fridericia's correction that is unmeasurable, or ? 480 msec on screening ECG. The average QTc from the screening ECG (completed in triplicate) must be < 480 msec in order for the patient to be eligible for the study;
Subjects taking any concomitant medication that may cause QTc prolongation, induce Torsades de Pointes are not eligible if QTc ? 460 msec.
Has QTc (QT interval corrected for rate) prolongation defined as: a) Symptomatic QTc prolongation >450 msec (males) or >470 msec (females) OR b) Any QTc prolongation of >500 msec
Prolonged QTc interval >450 msec
Patients with corrected QT (QTc) interval > 0.47 seconds
Patients with baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTc interval > 480 milliseconds, or history of congenital long QT syndrome, or torsades de pointes) are ineligible
Concurrent medications associated with a known risk of corrected QT interval (QTc) prolongation and/or Torsades de Pointes are not allowed within 2 weeks of initiation of study treatment; those medications listed as a possible risk for causing QTc prolongation and Torsades de Pointes will be allowed, although if an alternative medication can be substituted, that would be preferable; granisetron is an acceptable antiemetic on this study, but if a patient must take ondansetron, they may NOT take any other concomitant agents which might impact their QTc
Patients with current evidence of significant cardiovascular disease (New York Heart Association class III or IV cardiac disease), symptomatic congestive heart failure, dilated/hypertrophic or restrictive cardiomyopathy, myocardial infarction (within the past 6 months), unstable angina, unstable arrhythmia or a need for anti-arrhythmic therapy (use of medications for rate control for atrial fibrillation is allowed such as calcium channel blockers and beta-blockers, if stable medication for at least last month prior to initiation of romidepsin treatment and medication not listed as causing Torsades de Pointes), or evidence of acute ischemia on electrocardiogram (ECG); marked baseline prolongation of QT/QTc interval, e.g., repeated demonstration of a QTc interval > 450 msec*; long QT syndrome; the required use of concomitant medication that may cause Torsades de Pointes or may cause a significant prolongation of the QTc\r\n* Note: due to difficulties assessing QTc in patients with heart block, they may be eligible if deemed safe by a cardiologist; if a patient must take ondansetron as their antiemetic, their QTc may NOT be over 450 (no exception for patients with heart block)
Corrected QT (QTc) prolongation with other medications that required discontinuation of that medication
QTc with Bazett’s correction that is unmeasurable or >= 450 msec on screening electrocardiogram (ECG); (Note: if a subject has a QTc interval >= 450 msec on screening ECG, the screen ECG may be repeated twice [at least 24 hours apart]; the average QTc from the three screening ECGs must be < 450 msec in order for the subject to be eligible for the study)
Patient must not have corrected QT interval (QTc) > 480 msecs using Bazett’s formula
Cardiovascular risk, including:\r\n* Poorly controlled hypertension, defined as either systolic > 170 or diastolic > 110\r\n* Congestive heart failure\r\n* Myocardial infarction within the past year\r\n* QT prolongation, defined as pretreatment corrected QT interval (QTc) > 440 msec in males or > 460 msec in females
Serious ventricular arrhythmias or high risk for arrhythmias, due to prolongation of the QT-interval (> 60 milliseconds [msec])
Patient has any of the following cardiac abnormalities (as determined by treating Doctor of Medicine [MD]):\r\n* Symptomatic congestive heart failure\r\n* Myocardial infarction =< 6 months prior to enrollment\r\n* Unstable angina pectoris\r\n* Serious uncontrolled cardiac arrhythmia\r\n* Corrected QT interval (QTc) >= 480 msec (>= 500 msec in the presence of right bundle branch block [RBBB])
Corrected QT (QTc) prolongation > 480 msec, as calculated by either the Bazett or Fridericia formula, as per institutional standard
12-lead ECG with QTc interval within defined limit
Have corrected QT interval of >500 millisecond (msec) on screening electrocardiogram (ECG).
QTc interval <480 millisecond (msec).
Subjects with prolonged QT interval.
QTc prolongation >480 msec.
Have corrected QT interval of >470 milliseconds on screening electrocardiogram (ECG).