Trial of CPX-351 in Newly Diagnosed Elderly AML Patients

This study is a randomized, open-label, parallel-arm, fixed-dose, standard therapy controlled
Phase IIB trial. Study enrollment duration is expected to be approximately 12-18 months. On
entry, patients are randomized to receive either CPX-351 or standard induction treatment with
cytarabine and daunorubicin("7 and 3" regimen).

Patients are stratified to balance the likelihood of obtaining a CR and the duration of CR
between the two arms.

Inclusion Criteria:

- Age ≥60 and <76 years at the time of diagnosis of AML

- Pathological confirmation of AML

- 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 Serum alanine
aminotransferase or aspartate aminotransferase < 150 IU/liter Note: If elevated liver
enzymes are related to disease; contact medical monitor to discuss.

- Cardiac ejection fraction > 50% by echocardiography or MUGA scan

Exclusion Criteria:

- Patients with locally advanced or metastatic solid tumors ≤5 years from initial
diagnosis are excluded. (Patients with locally advanced or metastatic solid tumors >5
years from initial diagnosis, for whom the investigator has no clinical suspicion of
active disease for >2 years before randomization are eligible)

- Prior treatment for AML; only hydroxyurea is permitted (see below)

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

- Patients with a prior anthracycline exposure of greater than 368 mg/m2 daunorubicin
(or equivalent)

- Any serious medical condition, laboratory abnormality or psychiatric illness that
would prevent obtaining informed consent

- Administration of any antineoplastic therapy within 4 weeks of the first CPX-351 dose;
in the event of rapidly proliferative disease use of hydroxyurea is permitted until 24
hours before the start of study treatment

- Clinical evidence of active CNS leukemia

- 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 Class III or IV staging

- Active and uncontrolled infection. Patients with an infection receiving treatment with
antibiotics may be entered into the study if they are afebrile and hemodynamically
stable for 72 hrs.

- Current evidence of invasive fungal infection (blood or tissue culture); HIV or active
hepatitis C infection

- Hypersensitivity to cytarabine, daunorubicin or liposomal products

- History of Wilson's disease or other copper-related disorder