CPX-351 for the Treatment of Secondary Acute Myeloid Leukemia in Patients Younger Than 60 Years Old

PRIMARY OBJECTIVE:

I. To determine the complete response rate including morphologic complete remission (CR) and morphologic complete remission with incomplete blood count recovery (CRi) as defined by the International Working Group Criteria.

SECONDARY OBJECTIVE:

I. To determine CR + CRi duration, event free survival (EFS), overall survival (OS), patients successfully proceeding to allogenic hematopoietic cell transplant, and adverse events (AE).

OUTLINE:

INDUCTION: Patients receive liposome-encapsulated daunorubicin-cytarabine intravenously (IV) over 90 minutes on days 1, 3, and 5 in the absence of disease progression or unacceptable toxicity.

RE-INDUCTION: Patients who do not achieve remission receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3 in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: Beginning 5-8 weeks after the start of the last induction, patients who achieve CR receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3. Treatment repeats every 45 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, and then every 3 months for up to 5 years.

Inclusion criteria

• Newly diagnosed:

• Therapy-related acute myeloid leukemia (AML)
• AML with antecedent myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML)
• AML with MDS-related changes (as per World Health Organization [WHO])
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
• Plasma creatinine =< 1.5 x upper limit of normal (ULN)
• Total bilirubin < 2.0 mg/dL
• Serum alanine aminotransferase and aspartate aminotransferase < 3 x ULN
• Left ventricular ejection fraction by echocardiogram or multiple-gated acquisition >= 50%
• Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to enrollment and commit to two forms of birth control
• Men must use a latex condom during any sexual contact with women of childbearing potential
• Willing to adhere to protocol specific requirements
• Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion criteria

• Prior treatment of AML
• Known clinically active central nervous system (CNS) leukemia
• Core-binding factor leukemia
• Acute promyelocytic leukemia
• Uncontrolled other malignancy
• Prior anthracycline exposure > 368 mg/m^2 of daunorubicin or equivalent
• Cardiovascular disease resulting in heart failure (New York Heart Association class III or IV), unstable angina (angina symptoms at rest), or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months
• Hypersensitivity to cytarabine, daunorubicin, or liposomal drugs
• Known active HIV infection
• Known history of active hepatitis B or C infection
• Pre-existing liver disease (e.g. cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, sclerosing cholangitis)
• Evidence of ongoing, uncontrolled systemic infection
• Pregnant or breastfeeding women
• Subject with concurrent severe and/or uncontrolled medical or psychiatric conditions that in the opinion of the investigator may impair the participation in the study or the evaluation of safety and/or efficacy
• History of Wilson disease or other copper-handling disorders
• Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug