An Open Label Phase II Pharmacokinetic and Pharmacodynamic Assessment of the Potential for QTc Prolongation Following First Induction Treatment With CPX-351 (Cytarabine:Daunorubicin) Liposome Injection in Acute Leukemias and MDS Patients

Inclusion Criteria

• Ability to understand and voluntarily sign an informed consent form
• Age ≥ 18 to ≤ 80 years at the time of signing the informed consent form
• Life expectancy of at least 3 months
• Pathological confirmation by bone marrow documenting the following:
• Newly Diagnosed De novo AML according to WHO criteria except for Acute Promyelocytic Leukemia or patients with known favorable cytogenetics (see exclusion)
• Newly Diagnosed Secondary AML age 200 msec)
• Bundle branch block or QRS ≥ 120 msec
• Abnormal T wave morphology (other than slight flattening)
• Pathological U waves
• Other QRS or T/U morphology preventing accurate determination of QT interval
• Patients with unexplained syncope, history of or known risk factors for torsade des pointes, including congenital long QT syndrome, or family history of LQTS.
• Patients with history of and/or current evidence of myocardial impairment (e.g. cardiomyopathy, ischemic heart disease, significant valvular dysfunction, hypertensive heart disease, and congestive heart failure) resulting in heart failure by New York Heart Association Criteria (Class III or IV staging)
• Newly diagnosed patients with Acute promyelocytic leukemia [t(15;17)] or favorable cytogenetics, including t(8;21) or inv16
• Clinical evidence of active CNS leukemic involvement
• Chemotherapy or other investigational anticancer therapeutic drugs within 1 week prior to study entry unless AEs have resolved and there is no interference with the assessment of efficacy or safety; in the event of rapidly proliferative disease, however, the use of hydroxyurea is permitted up to 12 hours before study entry. Patients with prior bone marrow or stem cell transplant, considered for inclusion, should be discussed with the medical monitor first.
• Any serious medical condition or psychiatric illness that would prevent the patient from providing informed consent
• Patients with prior cumulative anthracycline exposure of greater than 368 mg/m2 daunorubicin (or equivalent)
• Active or uncontrolled infection. Patients with any infection receiving treatment (antibiotic, antifungal or antiviral treatment) may be entered into the study but must be afebrile and hemodynamically stable for ≥72 hrs. Patients with fevers believed to be due to leukemia or MDS are eligible provided a thorough infection work-up is negative and the patient is clinically and hemodynamically stable.
• Pregnant or lactating women
• Hypersensitivity to cytarabine, daunorubicin or liposomal products
• History of Wilson's disease or other copper-related metabolic disorder