cpx-351 in combination with gemtuzumab ozogamicin in newly diagnosed aml

Conditions: Acute Myeloid Leukemia

Summary: the purpose of the study is to determine the safety of combining the drugs gemtuzumab ozogamicin (go) with cpx-351 in order to treat the disease, as well as to find the maximum tolerated dose level and recommended phase 2 dose level of go with a fixed dose of cpx-351.


Eligibility criteria:
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 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 * 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. * participants must have acceptable organ function * adequate cardiac function defined as ejection fraction of ≥50% as determined by multigated acquisition scan (muga) or 2d echocardiogram. * hydroxyurea is allowed for cytoreduction until day 1 of study treatment exclusion criteria: * prior treatment of aml except hydroxyurea and/or leukapheresis * participants 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. * participants 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/m2 of daunorubicin (or equivalent). for participants who have received radiation therapy to the mediastinum, the total cumulative dose of anthracycline should not exceed 400 mg/m2 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 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