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NCT Number: NCT07828535

Liposomal Mitoxantrone Plus Azacitidine and Venetoclax in Newly Diagnosed Elderly or Unfit AML

This prospective, open-label, multicenter phase Ib trial will evaluate the safety, tolerability, and RP2D of the VAM regimen (liposomal mitoxantrone + azacitidine [AZA] + venetoclax [VEN]) in elderly or unfit patients with newly diagnosed AML. A standard 3+3 dose escalation will enroll 12-30 patients, testing liposomal mitoxantrone at 8, 12, 16, and 20 mg/m². VEN duration (9 vs. 14 days) will be determined at the 8 mg/m² dose level, after which only liposomal mitoxantrone will be escalated while AZA and VEN will remain fixed.

Induction therapy will consist of up to two 28-day cycles. Responders achieving CR/CRi/MLFS will be eligible for up to 4 consolidation cycles (total ≤6 cycles), after which they will proceed to maintenance with either AZA+VEN or observation.

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Key information

Conditions

Acute Myeloid Leukemia (AML) Hematologic Diseases Hemic and Lymphatic Diseases Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Neoplasms Neoplasms by Histologic Type

Age range

18 year–99 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Subjects eligible for enrollment in this study must meet all of the following criteria:
  • Diagnosis of acute myeloid leukemia (AML) according to the WHO 2022 or ICC criteria, excluding acute promyelocytic leukemia (APL).
  • No prior therapy for AML, except hydroxyurea for the management of hyperleukocytosis.
  • Meeting at least one of the following criteria:
  • Age ≥ 75 years;
  • Age 18-74 years with at least one of the following conditions precluding suitability for intensive chemotherapy:

i. ECOG performance status 2-3; ii. Cardiac dysfunction with left ventricular ejection fraction (LVEF) ≤ 50%; iii. Pulmonary dysfunction with diffusing capacity of the lung for carbon monoxide (DLCO) ≤ 65% or forced expiratory volume in 1 second (FEV1) ≤ 65%; iv. Creatinine clearance 30-45 mL/min; v. Other major organ dysfunction or comorbidities that, in the investigator's judgment, render the patient unsuitable for intensive chemotherapy.

  • ECOG performance status 0-3.
  • Life expectancy ≥ 3 months.
  • Patients of childbearing potential agree to use effective contraception during the treatment period and for at least 6 months after the last dose of study treatment.
  • Voluntary written informed consent provided.

Exclusion criteria

  • Subjects who meet any of the following criteria will not be eligible for enrollment in this study:
  • Acute promyelocytic leukemia (APL)..
  • Active central nervous system (CNS) leukemia.
  • Prior targeted therapy or chemotherapy for AML, excluding hydroxyurea.
  • Uncontrolled active infection.
  • Uncontrolled cardiovascular disease: New York Heart Association (NYHA) class III-IV heart failure, myocardial infarction or unstable angina within 6 months before enrollment, or uncontrolled hypertension.
  • Left ventricular ejection fraction (LVEF) < 40%.
  • Concurrent active malignancy, except for cured non-melanoma skin cancer, carcinoma in situ of the cervix, or localized prostate cancer.
  • Known hypersensitivity to the study drugs or their excipients.
  • Pregnant or breastfeeding women.
  • Any other condition that, in the investigator's judgment, would make the patient unsuitable for study participation.

Treatment and study plan

Liposome mitoxantrone

Drug

Liposome Mitoxantrone: 8, 12, 16, and 20 mg/m², administered by intravenous drip (ivgtt) on day 1, every 4 weeks

Venetoclax

Drug

Venetoclax(9 days): 100 mg on day 1, 200 mg on day 2, and 400 mg on days 3-9, administered orally (po), every 4 weeks Venetoclax(14 days): 100 mg on day 1, 200 mg on day 2, and 400 mg on days 3-14, administered orally (po), every 4 weeks

Azacitidine

Drug

Azacitidine: 75 mg/m², administered subcutaneously (sc) on days 1-7, every 4 weeks

Primary outcomes

  1. Dose-Limiting Toxicity (DLT)

    Time frame: Cycle 1(up to 42 days)

    To evaluate the safety, tolerability, and RP2D of the VAM regimen in newly diagnosed elderly/unfit AML patients.

  2. Incidence of treatment-related adverse events

    Time frame: From day 1 of treatment to 28 days after the last dose

    The safety of the drug was evaluated by NCI-CTC AE 5.0 standard which including hematologic and non-hematologic toxicity

  3. Composite complete remission (CRc) rate

    Time frame: Up to approximately eight weeks

    Proportion of patients with complete remission (CR), complete remission with incomplete hematologic recovery (CRi) or morphologic leukemia-free state (MLFS)

Secondary outcomes

  1. Complete remission (CR) rate

    Time frame: Up to approximately eight weeks

    Proportion of patients with complete remission (CR)

  2. Complete remission with incomplete hematologic recovery (CRi) rate

    Time frame: Up to approximately eight weeks

    Proportion of patients with complete remission with incomplete hematologic recovery (CRi)

  3. Morphologic leukemia-free state (MLFS) rate

    Time frame: Up to approximately eight weeks

    Proportion of patients with morphologic leukemia-free state (MLFS)

  4. Event-free survival (EFS)

    Time frame: Up to approximately 5 years

    It is defined as the time from the start of study treatment to the occurrence of induction failure or disease progression or death from any cause (whichever occurs first)

  5. Overall survival (OS)

    Time frame: Up to approximately 5 years

    It is defined as the time from the start of study treatment to the death from any cause

  6. Relapse-free Survival (RFS)

    Time frame: Up to approximately 5 years

    It is defined as the time from the start of achieving remission to disease progression, death from any cause or the last follow-up

  7. Duration of Response (DoR)

    Time frame: Up to approximately 5 years

    It is defined as the time from the first documentation of CRc to relapse

  8. 30-day postinduction mortality

    Time frame: Up to approximately 30 days

    It is defined as death from any cause within 30 days after the start of induction

  9. 60-day postinduction mortality

    Time frame: Up to approximately 60 days

    t is defined as death from any cause within 60 days after the start of induction

  10. Measurable Residual Disease (MRD) negative rate by flow cytometry

    Time frame: Up to approximately eight weeks

    Among those who have achieved CR/CRh/CRi after induction, proportion of patients who is MRD-negative by flow cytometry

  11. Measurable Residual Disease (MRD) negative rate by molecular testing

    Time frame: Up to approximately eight weeks

    Among those who have achieved CR/CRh/CRi after induction, proportion of patients who is MRD-negative by molecular testing

Sponsors and collaborators

Lead sponsor

Institute of Hematology & Blood Diseases Hospital, China

Other

Registry information

Official study title

A Phase Ib Study of Liposomal Mitoxantrone Combined With Azacitidine and Venetoclax in Newly Diagnosed Elderly or Unfit Patients With Acute Myeloid Leukemia

Important dates

Study start
2026
Primary completion
2027
Study completion
2032
First posted
Sep 18, 2026
Registry last updated
Sep 18, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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