CPX-351 in Combination With Gemtuzumab Ozogamicin in 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

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Vyxeos; Drug: Gemtuzumab Ozogamicin

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Lisa Nardelli; Phone Number: 1-813-745-4731; Email: Lisa.Nardelli@moffitt.org

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
      • Contact: Lisa Nardelli; Phone Number: 813-745-4731; Email: lisa.nardelli@moffitt.org
      • Principal Investigator: Onyee Chan, MD
      • Contact: Onyee Chan; Phone Number: 1-813-745-2069; Email: Onyee.Chan@moffitt.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Dose Escalation; Dose escalation to determine the maximum tolerated dose (MTD) of CPX-351 in combination with Gemtuzumab Ozogamicin in participants with newly diagnosed acute myeloid leukemia. Participants will be treated in cohorts of size three to six and the dosage will be escalated if the clinical toxicity is acceptable. A total of 3 dose levels will be used.

Drug: Vyxeos; Fixed dose of Vyxeos (44 mg/m2 daunorubicin and 100 mg/m2 cytarabine) (Day 1, 3, and 5) in combination with various dose schedules of Gemtuzumab Ozogamicin (GO); Other Names: CPX-351; daunorubicin-cytarabine; Drug: Gemtuzumab Ozogamicin; Participants will be treated at the following dose levels: Dose Level 1 - Gemtuzumab Ozogamicin will administered 3mg/m2 on Day 1 Dose Level 2 - Gemtuzumab Ozogamicin will administered 3mg/m2 on Day 1 and 4 Dose Level 3 - Gemtuzumab Ozogamicin will administered 3mg/m2 on Day 1, 4, 7; Other Names: Mylotarg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD)	Dose escalation will determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Vyxeos plus Gemtuzumab Ozogamicin. The MTD is the highest dose of the combination therapy that dose not cause unacceptable side effects.	Up to 18 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Complete Remission	Rate of complete remission (CR) and complete remission with incomplete blood count recovery (CRi). The definition of CR and CRi is based on the European LeukemiaNet 2017 Response Criteria for AML.	Up to 18 Months
Measurable Residual Disease	Rate of measurable residual disease via RT-PCR for core binding factor leukemia as well as NPM1 mutated AML	Up to 18 Months
Overall Survival	Overall survival is defined as the duration of time from start of treatment to the time of death from any cause or date of last contact.	Up to 5 years
Relapse Free Survival (RFS)	RFS is defined as time interval between achievement of CR to time of relapse	Up to 18 Months

Collaborators and Investigators

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborators: Jazz Pharmaceuticals
• Investigators: Principal Investigator: Onyee Chan, MD, Moffitt Cancer Center

Publications and helpful links

Helpful Links

• Moffitt Cancer Center Clinical Trial Search

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2023
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: September 22, 2022
• First Submitted That Met QC Criteria: September 23, 2022
• First Posted (Actual): September 28, 2022

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Amino Acids, Peptides, and Proteins; Proteins; Carbohydrates; Glycosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Aminoglycosides; Calicheamicins; Gemtuzumab; CPX-351
• Other Study ID Numbers: MCC-21450

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes