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

NCT07828535 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: IIT2026104
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Acute Myeloid Leukemia (AML)

Outcome Measures

Primary Outcomes (3)

• Dose-Limiting Toxicity (DLT)

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

  Cycle 1(up to 42 days)

• Incidence of treatment-related adverse events

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

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

• Composite complete remission (CRc) rate

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

  Up to approximately eight weeks

Secondary Outcomes (11)

• Complete remission (CR) rate

  Up to approximately eight weeks

• Complete remission with incomplete hematologic recovery (CRi) rate

  Up to approximately eight weeks

• Morphologic leukemia-free state (MLFS) rate

  Up to approximately eight weeks

• Event-free survival (EFS)

  Up to approximately 5 years

• Overall survival (OS)

  Up to approximately 5 years

Study Arms (1)

Venetoclax, azacitidine combined with liposome mitoxantrone as induction regimen

EXPERIMENTAL

The trial will employ a standard 3+3 dose escalation design, 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. Venetoclax duration will be sequentially escalated (9 vs. 14 days), choosing the longest duration without dose-limiting toxicity (DLT) in 3-6 evaluable patients. The RP2D for liposomal mitoxantrone is the highest dose with ≤1 DLT in 6 patients; if DL4 is tolerated, RP2D = 20 mg/m² on day 1.

Drug: Liposome Mitoxantrone; Drug: Venetoclax; Drug: Azacitidine

Interventions

Liposome Mitoxantrone DRUG

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

Venetoclax, azacitidine combined with liposome mitoxantrone as induction regimen

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

Venetoclax, azacitidine combined with liposome mitoxantrone as induction regimen

Azacitidine DRUG

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

Venetoclax, azacitidine combined with liposome mitoxantrone as induction regimen

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

venetoclax; Azacitidine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Design

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

Study Record Dates

• First Submitted: September 15, 2026
• First Posted: September 18, 2026
• Study Start (Estimated): October 30, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2032
• Last Updated: September 18, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share