A Phase I Clinical Trial of OXi4503 for Relapsed and Refractory AML and MDS

Exclusion Criteria

• •Acute promyelocytic leukemia (APL) with t(15;17);
• •Absolute peripheral blood myeloblast count greater than 25,000/mm3;
• •Uncontrolled hypertension, defined as blood pressure 140/90 mm Hg despite maximum medical intervention;
• •History of congenital long QT syndrome or torsades de pointes;
• •Pathologic bradycardia or heart block (excluding first degree heart block);
• •Prolonged baseline QTc, defined as QTc interval \> 470 msec in women and \> 450 msec in men;
• •History of ventricular arrhythmia (excluding premature ventricular contractions, PVCs);
• •Major operative surgery within 28 days;
• •Unstable angina pectoris within 28 days;
• •Myocardial infarction and/or new ST elevation or depression or new Q wave on ECG within 28 days;
• •Any history of hemorrhagic stroke;
• •Symptomatic congestive heart failure Class III or greater (New York Heart Association Functional Classification);
• •On full dose anti-coagulation defined as warfarin intended to raise the INR to 2-3, or enoxaparin 1 mg/kg twice a day or unfractionated heparin intended to raise the PTT to 60-90 seconds;
• •Major hemorrhagic event within 28 days requiring transfusion of packed red blood cells;
• •Prior history of hypertensive crisis or hypertensive encephalopathy;
• •Active, uncontrolled, clinical significant infection;
• •Any open wound;
• •Pregnant and nursing patients are excluded because the effects of OXi4503 on a fetus or nursing child are unknown.
• •Treatment with any anticancer therapy (standard or investigational) within the previous 21 days prior to the first dose of study drug or less than full recovery (CTCAE grade 1) from the clinically significant toxic effects of that treatment. The use of hydroxyurea may be used for two weeks after dosing in Cycle 1 (e.g., Days 1-14 dosed with hydroxyurea).
• •Patients on concurrent medications known to prolong the QTc interval may participate as long as their screening QTc interval meets eligibility criteria.