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

NCT04990102 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STUDY00003287
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 3

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

Keywords

Acute Myeloid Leukemia; Remission

Outcome Measures

Primary Outcomes (2)

• Maximum tolerate dose (Phase 1)

  Number of subjects with Dose Limiting toxicities will be used to determine the recommended phase II dose of CPX-351 to be used in the maintenance setting for newly diagnosed AML in complete remission.

  1 cycle (28 day cycle)

• Inicidence of Treatment Emergent Adverse events (Phase 2)

  To determine the safety, tolerability and toxicity of CPX-351 in the maintenance setting for newly diagnosed AML in complete remission by analyzing the incidence of treatment emergent adverse events reported.

  6 cycles (28 day cycles)

Secondary Outcomes (4)

• Incidence of Treatment Emergent Adverse Events (Phase 1)

  6 cycles (28 day Cycle)

• Overall Survival (Phase 1 and 2)

  1 year after end of treatment

• Event free survival (Phase 1 and 2)

  1 year after end of treatment

• Relapse Free Survival (Phase 1 and 2)

  1 year after end of treatment

Study Arms (1)

CPX-351

EXPERIMENTAL

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.

Drug: CPX-351

Interventions

CPX-351 DRUG

Daunorubicin 8.8mg/m2 + cytarabine 20mg/m2

Also known as: Vyxeos

CPX-351

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 12 cycles 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

You may not qualify if:

• 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 low risk prostate cancer or 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.

Sponsors & Collaborators

• Georgetown University: lead
• Jazz Pharmaceuticals: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (3)

Georgetown Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

RECRUITING

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

CPX-351

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Kimberley Doucette, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Dose de-escalation of CPX-351

Study Record Dates

• First Submitted: July 26, 2021
• First Posted: August 4, 2021
• Study Start: May 22, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)