Phase III Study of CPX-351 Versus 7+3 in Patients 60-75 Years Old With Untreated High Risk (Secondary) Acute Myeloid Leukemia

Inclusion Criteria:

• Ability to understand and voluntarily give informed consent

• Age 60-75 years at the time of diagnosis of AML

• Pathological diagnosis of AML according to WHO criteria (with at least 20% blasts inthe peripheral blood or bone marrow)

• Confirmation of:

• Therapy related AML: t-AML must have a documented history of prior cytotoxictherapy or ionizing radiotherapy for an unrelated disease

• AML with a history of myelodysplasia: MDSAML must have bone marrow documentationof prior MDS

• AML with a history of CMMoL: CMMoLAML must have bone marrow documentation ofprior CMMoL

• De novo AML with karyotypic abnormalities characteristic of MDS: de novoAML musthave cytogenetics with abnormalities per WHO.

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Able to adhere to the study visit schedule and other protocol requirements

• Laboratory values fulfilling the following:

• Serum creatinine < 2.0 mg/dL

• Serum total bilirubin < 2.0 mg/dL, patients with Gilbert's Syndrome shouldcontact the medical monitor

• Serum alanine aminotransferase or aspartate aminotransferase < 3 times the ULNNote: If elevated liver enzymes, above the ULN, are related to disease; contactmedical monitor to discuss.

• Cardiac ejection fraction ≥ 50% by echocardiography or MUGA

• Patients with second malignancies in remission may be eligible if there is clinicalevidence of disease stability for a period of greater than 6 months off cytotoxicchemotherapy, documented by imaging, tumor marker studies, etc., at screening.Patients maintained on long-term non-chemotherapy treatment, e.g., hormonal therapy,are eligible.

Exclusion Criteria:

• Except for CMMoL, patients with history of myeloproliferative neoplasms (MPN) (definedas a history of essential thrombocytosis or polycythemia vera, or idiopathicmyelofibrosis prior to the diagnosis of AML) or combined MDS/MPN are not eligible.

• Acute promyelocytic leukemia [t(15;17)] or favorable cytogenetics, including t(8;21)or inv16 if known at the time of randomization.

• Clinical evidence of active CNS leukemia

• Patients with active (uncontrolled, metastatic) second malignancies are excluded.

• Prior treatment intended for induction therapy of AML; only hydroxyurea is permittedfor control of blood counts. For example, a patient with MDS that changes HMA dose andschedule after the diagnosis of AML is excluded. AML-type therapy, such as cytarabinealone (>1g/m2/day) or cytarabine plus an anthracycline as well as prior HSCT are alsoexcluded.

• Administration of any therapy for MDS (conventional or investigational) must becompleted by 2 weeks prior to of the first dose of study drug; in the event of rapidlyproliferative disease use of hydroxyurea is permitted until 24 hours before the startof study treatment. Toxicities associated with prior MDS therapy must have recoveredto grade 1 or less prior to start of treatment.

• Any major surgery or radiation therapy within four weeks.

• Patients with prior cumulative anthracycline exposure of greater than 368 mg/m2daunorubicin (or equivalent).

• Any serious medical condition, laboratory abnormality or psychiatric illness thatwould prevent obtaining informed consent

• Patients with myocardial impairment of any cause (e.g. cardiomyopathy, ischemic heartdisease, significant valvular dysfunction, hypertensive heart disease, and congestiveheart failure) resulting in heart failure by New York Heart Association Criteria (Class III or IV staging)

• Active or uncontrolled infection. Patients with an infection receiving treatment (antibiotic, antifungal or antiviral treatment) may be entered into the study but mustbe afebrile and hemodynamically stable for ≥72 hrs.

• Current evidence of invasive fungal infection (blood or tissue culture); patients withrecent fungal infection must have a subsequent negative cultures to be eligible; knownHIV (new testing not required) or evidence of active hepatitis B or C infection (withrising transaminase values)

• Hypersensitivity to cytarabine, daunorubicin or liposomal products

• History of Wilson's disease or other copper-metabolism disorder