Evaluation of CPX-351 Monotherapy in Acute Myeloid Leukemia Secondary to Myeloproliferative Neoplasm

Inclusion Criteria:

• Diagnosis of newly secondary AML according to WHO 2016 classification following anantecedent of Myeloproliferative Neoplasm including Essential Thrombocythemia (ET),Polycythemia Vera (PV), primary or secondary Myelofibrosis

• Performance status 2 Eastern Cooperative Oncology Group (ECOG) grading.

• Eligible for standard intensive chemotherapy

• Absence of concomitant severe cardiovascular disease which would make intensivechemotherapy impossible, i.e. arrhythmias requiring chronic treatment, congestiveheart failure or symptomatic ischemic heart disease, reduced left ventricularfunction assessed by multigated acquisition (MUGA) scan or echocardiogram. Cardiacejection fraction ≥ 50% by echocardiography ou MUGA

• Patient must have adequate organ function as indicated by the following laboratoryvalues:

• Renal

• Serum creatinine: < 2 mg/dl OR calculated creatinine clearance*: ≥ 30mL/min by MDRD formula for patients with creatinine levels > 1.5 Xinstitutional Upper Limit Normal (ULN)

• Hepatic

• Serum total bilirubin: ≤ 2.5 X ULN OR direct bilirubin ≤ ULN for patientswith total bilirubin levels ≥ 2 mg/dL unless Gilbert's Syndrome

• Aspartate-Amino-Transferase (ASAT) and Alanine-Transaminase (ALAT): ≤ 2.5times ULN

• Alkaline Phosphatase: ≤ 5 X ULN, if > 2.5 X ULN, then liver fractionshould be ≤ 2.5 X ULN *Creatinine clearance should be calculated perinstitutional standard

• Life expectancy should be of 12 weeks at least according to investigator evaluation

• Female patients of childbearing potential must have a negative serum pregnancy test (β-hCG) within 72 hours prior to receiving the first dose of CPX-351. Femalepatients who are not post-menopausal, free from menses for > 2 years or surgicallysterilized, will have to use adequate barrier methods of contraception to preventpregnancy or agree to abstain from becoming pregnant throughout the study, startingwith Visit 1.

• Male patients agree to use an adequate method of contraception for the duration ofthe study. Men should be advised not to father a child while receiving CPX-351 andfor 3 months post study.

• Patients have the ability to understand and willingness to sign an informed consentform indicating the investigational nature of the study.

Exclusion Criteria:

• MPN/MDS mixed types

• Prior therapy for AML transformation except for Hydroxyurea

• Prior treatment with growth factors such as erythropoietin alfa (EPO) or granulocytecolony-stimulating factor (G-CSF), low-dose oral chemotherapy or Hypomethylatingagents chemotherapy given in the chronic phase of MPN in the 30 days beforeinclusion, except for hydroxyurea.

• Uncontrolled undercurrent illness or circumstances that could limit compliance withthe study, including but not limited to the following: symptomatic congestive heartfailure, unstable angina pectoris, uncontrolled cardiac arrhythmia, pancreatitis, orpsychiatric or social conditions that may interfere with patient compliance.

• Active and uncontrolled infection

• Current participation or participation in a study with an investigational compoundor device within 30 days of initial dosing with study drug

• Patients with acute promyelocytic leukemia.

• Known human immunodeficiency virus (HIV) infection or HIV-related malignancy

• Clinically active hepatitis B or hepatitis C infection.

• Known allergy or hypersensitivity to any component of CPX-351.

• Currently active second malignancy, other than non-melanoma skin cancer and in situcarcinoma of the cervix. Patients are not considered to have a "currently active"malignancy if they have completed therapy for a prior malignancy, are disease freefrom prior malignancies for >3 years or are considered by their physician to be atless than 30% risk of relapse

• Clinical evidence of Central Nervous System Leukemia.

• Pregnancy or breastfeeding during the projected duration of the study.