Trial of CPX-351 in Newly Diagnosed Elderly AML Patients

Phase IIB, Multicenter, Randomized, Open Label Trial of CPX-351 (Cytarabine:Daunorubicin) Liposome Injection Versus Cytarabine and Daunorubicin in Patients With Untreated AML 60-75 Years of Age.

The study investigates if CPX-351 will be a) more effective than the standard AML treatment and b) more tolerable than the standard AML treatment regimens.

The study compares the investigational product CPX-351 vs the standard treatment for AML in this patients age group.

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