Phase IB/II of CPX-351 for Relapse Prevention in AML

NCT ID: NCT04990102

Last Updated: 2025-07-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-22
• Study Completion Date: 2025-12-31

Brief Summary

This is a phase IB/II study with a 3+3 dose de-escalation study design. Patients will continue maintenance treatment with CPX-351 for 6 cycles on D1 and D3, as long as patient remains in CR. The dose de-escalation will be one dose given on D1 only, every 28 days pending toxicity. The maximum tolerated dose will be used for the phase II expansion portion of the study.

Conditions

Acute Myeloid Leukemia (AML) in Remission

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CPX-351

Dose Level 1: CPX-351 administered through intravenou infusion on Day 1 and Day 3 of 28 day cycle for 6 cycles or Dose Level -1: CPX-351 administered through intravenous infusion on Day 1 of each 28 day cycle for 6 cycles.

Group Type: EXPERIMENTAL

CPX-351

Intervention Type: DRUG

Daunorubicin 8.8mg/m2 + cytarabine 20mg/m2

Interventions

CPX-351

Daunorubicin 8.8mg/m2 + cytarabine 20mg/m2

Intervention Type: DRUG

Other Intervention Names

Vyxeos

Eligibility Criteria

Inclusion Criteria

• Newly diagnosed patients > 18 years of age
• Patients must be in CR or CRh (complete remission with partial count recovery).
• Must have received ANY induction treatment with standard consolidation or hypomethylating agent (HMA) + venetoclax, for up to 6 cycles or no more than one year of treatment.
• Must be able to start therapy within 3 months of last documented CR
• De novo or secondary AML/treatment related AML (non-M3) including AML with myelodysplasia-related changes (MRC), histologically confirmed
• Patients must be ineligible for allogeneic BMT (for any reason including poor performance status, patient's preference, favorable AML not a candidate for transplant, or comorbidities and age precluding from transplant etc)
• Cardiac ejection fraction ≥ 50% by transthoracic echocardiography or MUGA scan
• Adequate hepatic and renal function defined as:

• Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 3 x upper limit of normal (ULN)
• Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 3 is permissible if due to disease.
• Bilirubin ≤3 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
• Estimated Creatinine Clearance ≥30 ml/min (Cockcroft-Gault based on actual weight) (See Appendix A)
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 3 (Appendix A)
• Female subjects who are of non-reproductive potential (i.e., post-menopausal by history - no menses for ≥1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy). Female subjects of childbearing potential must have a negative serum pregnancy test upon study entry.
• Male and female subjects who agree to use highly effective methods of birth control (e.g., condoms, implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], sexual abstinence, or sterilized partner) during the period of therapy and for at least 6 months after the last dose of study drug

Exclusion Criteria

• Prior allogeneic transplant
• Previous cumulative anthracycline (doxorubicin equivalent) dose equal to or greater than 345 mg/m2, and for patients with prior mediastinal XRT, anthracycline dose equal to or greater than 295 mg/m2
• Acute promyelocytic leukemia [t(15;17)]
• If patient is unable to sign informed consent due to any serious medical condition, laboratory abnormality or psychiatric illness
• Patients with evidence of uncontrolled current myocardial impairment (e.g. unstable ischemic heart disease, uncontrolled arrhythmia, symptomatic valvular dysfunction not controlled on medical therapy, uncontrolled hypertensive heart disease, and uncontrolled congestive heart failure)
• History of Wilson's disease or other copper-related disorders
• History of allergic reactions attributed to compounds of similar composition to cytarabine and daunorubicin or liposomal products
• History of other malignancies, except:

• Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• Adequately treated carcinoma in situ without evidence of disease.
• Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia
• Known active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV).
• Subjects who are positive for hepatitis B core antibody, hepatitis B surface antigen, hepatitis C antibody, must have a negative polymerase chain reaction (PCR) result for the respective disease before enrollment. Those who are PCR positive will be excluded.
• Any uncontrolled active systemic infection.
• Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk.
• Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization.
• Known CNS involvement by leukemia
• Erythema multiforme, toxic epidermal necrolysis, or Stevens-Johnson syndrome
• Lactating or pregnant.
• Unwilling or unable to participate in all required study evaluations and procedures.
• Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations).
• Currently active, clinically significant hepatic impairment (≥ moderate hepatic impairment according to the Child Pugh classification (class B or C))

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jazz Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Georgetown University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kimberley Doucette, MD

Role: PRINCIPAL_INVESTIGATOR

Georgetown University

Locations

Georgetown Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, United States

Site Status: RECRUITING

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status: RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Facility Contacts

Courtney Brown, RN

Role: primary

courtney.brown@georgetown.edu

202-687-0354

Oncology Clinical Research Referral Office

Role: primary

OncologyResearchReferral@hmhn.org

551-996-1777

Ashlena Livingston

Role: primary

Ashlena.Livingston@pennmedicine.upenn.edu

267-357-2228

Other Identifiers

STUDY00003287

Identifier Type: -

Identifier Source: org_study_id