13. Significant active cardiovascular or pulmonary disease including: Uncontrolled hypertension (i.e., systolic blood pressure >180 mm Hg, diastolic blood pressure > 95 mm Hg). Use of anti-hypertensive agents to control hypertension before Cycle1 Day 1 is allowed. Pulmonary hypertension. Uncontrolled asthma or O2 saturation < 90% by arterial blood gas analysis or pulse oximetry on room air. Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement. Medically significant (symptomatic) bradycardia. History of arrhythmia requiring an implantable cardiac defibrillator. 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).