CPX-351 in Combination With Gemtuzumab Ozogamicin in Newly Diagnosed AML

• Status: Recruiting
• Trial end date: 2025-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborator: Jazz Pharmaceuticals
• Treatments: Cytarabine; Daunorubicin; Gemtuzumab

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 favorable or intermediate 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 adverse risk AML as defined by ELN 2017 criteria

• Participants with acute promyelocytic leukemia (APL).

• Known 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