Combining CPX-351 with Gemtuzumab Ozogamicin for Newly Diagnosed AML

A Phase 1/1b Dose Escalation and Expansion of CPX-351 in Combination With Gemtuzumab Ozogamicin in Newly Diagnosed Acute Myeloid Leukemia

This study is testing a combination of two treatments, CPX-351 and gemtuzumab ozogamicin, to see if they are safe and effective for adults with newly diagnosed acute myeloid leukemia (AML).

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: H. Lee Moffitt Cancer Center and Research Institute (other)
• Drugs / interventions: Gemtuzumab, chemotherapy, radiation
• Locations: 1 site (Tampa, Florida)
• Trial ID: NCT05558124 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the safety and determine the maximum tolerated dose of the combination of CPX-351 and gemtuzumab ozogamicin in patients with newly diagnosed acute myeloid leukemia (AML). Participants will receive these treatments to assess their effectiveness and safety profile. The study will involve adult patients aged 18 to 70 years who meet specific eligibility criteria. The goal is to establish a recommended dose level for future phases of research.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 years with newly diagnosed acute myeloid leukemia.

Not a fit: Patients outside the age range of 18 to 70 years or those with other types of leukemia may not benefit from this study.

Why it matters

Potential benefit: If successful, this combination therapy could provide a new treatment option for patients with newly diagnosed AML.

How similar studies have performed: While this approach is being explored, similar combinations have shown promise in other studies, indicating potential for success.

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

Where this trial is running

Tampa, Florida

• Moffitt Cancer Center — Tampa, Florida, United States (RECRUITING)

Study contacts

• Principal investigator: Onyee Chan, MD — Moffitt Cancer Center
• Study coordinator: Lisa Nardelli

Conditions: Acute Myeloid Leukemia