CPX-351 with Gemtuzumab Ozogamicin for the Treatment of Patients with Newly Diagnosed Acute Myeloid Leukemia

Inclusion Criteria

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged >= 18 and =< 70 years with newly diagnosed any risk AML as defined by European LeukemiaNet (ELN) 2017 criteria
• For females of child-bearing potential: use of highly effective contraception upon enrollment and during study participation and for an additional 6 months after the end of CPX-351 and gemtuzumab ozogamicin administration * A female of child-bearing potential is considered when a sexually mature female: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months
• The effects of CPX-351 and gemtuzumab ozogamicin on the developing human fetus are unknown. For this reason, women of child-bearing potential as defined above must have a negative serum or urine pregnancy test within 24 hours prior to beginning study treatment
• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner
• Myeloblasts expressing CD33 as determined by flow cytometry or immunohistochemistry
• Eastern Cooperative Oncology Group (ECOG) =< 2 and eligible to receive intensive chemotherapy as determined by the treating physician
• Prior malignancy is allowed providing it does not require concurrent therapy. Exception: Active hormonal therapy is allowed
• Prior hypomethylating agents (HMA) therapy including azacitidine or decitabine when used for non-AML diagnoses is allowed. Most recent dose must have been >= 14 days prior to day 1 of study treatment
• Total bilirubin =< 1.5 times the institutional upper limit of normal, with a direct bilirubin that is within normal limits (for patients with Gilbert’s syndrome and serum bilirubin > 1.5x the upper limit of normal, the medical monitor/principal investigator (PI) should be contacted)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2.5 times the institutional upper limit of normal
• Creatinine =< 2 mg/dL OR creatinine clearance > 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
• Adequate cardiac function defined as ejection fraction of >= 50% as determined by multigated acquisition scan (MUGA) or two-dimensional (2D) echocardiogram
• Hydroxyurea is allowed for cytoreduction until day 1 of study treatment

Exclusion Criteria

• Prior treatment of AML except hydroxyurea and/or leukapheresis
• Patients with acute promyelocytic leukemia (APL)
• Known current and clinically active central nervous system (CNS) leukemia
• Severe liver disease (cirrhosis, non-alcoholic steatohepatitis, sclerosing cholangitis) or patients with known Wilson’s disease
• Patients with known active infection with hepatitis B or hepatitis C virus
• Known allergic reactions to components of the CPX-351 (cytarabine or daunorubicin) or gemtuzumab ozogamicin.
• Patients with any prior anthracycline exposure plus any planned on-study anthracycline exposure cannot not exceed 550 mg/m^2 of daunorubicin (or equivalent). For patients who have received radiation therapy to the mediastinum, the total cumulative dose of anthracycline should not exceed 400mg/m^2 of daunorubicin (or equivalent)
• Hemodynamically unstable (subjects requiring vasopressor support will not be eligible)
• Treatment with another investigational drug within 14 days
• Uncontrolled cardiac disease including congestive heart failure class III or IV by the New York Heart Association (NYHA), unstable angina (angina symptoms at rest), new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months
• Any disorder that compromises the subject’s ability to give written informed consent and/or to comply with study procedures
• Any substance abuse, severe and/or uncontrolled medical, social or psychiatric conditions that may prevent the subject from completing the study, interfere with the evaluation of safety and/or efficacy, or interfere with the interpretation of the study results
• Female subject who is pregnant or breastfeeding
• Any patient with a known FLT3 ITD or FLT3 TKD mutation