Venetoclax, Azacitidine and Liposomal Mitoxantrone for Newly Diagnosed AML

A Phase I/II, Single-Arm, Open-Label Study of Venetoclax, Azacitidine, and Liposomal Mitoxantrone (VAM) as Induction Therapy in Newly-diagnosed Adult Patients With Acute Myeloid Leukemia (AML)

This is a Phase I/II, single-arm, open-label clinical trial evaluating the safety and preliminary efficacy of a novel induction regimen combining Venetoclax, Azacitidine, and Liposomal Mitoxantrone (VAM) in adult patients with newly diagnosed Acute Myeloid Leukemia (AML) who are eligible for intensive chemotherapy.

The study plans to enroll 30 participants. Patients will receive VAM induction therapy, followed by three cycles of intermediate-dose cytarabine consolidation. Allogeneic hematopoietic stem cell transplantation is recommended for high-risk or MRD-positive patients in remission.

Study Overview

• Status: Not yet recruiting
• Conditions: AML
• Intervention / Treatment: Drug: Liposomal Mitoxantrone; Drug: Cytarabine; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation (HSCT); Drug: Venetoclax; Drug: Azacitidine

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hui Wei, MD; Phone Number: 13132507161; Email: weihui@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients diagnosed with AML according to the WHO (2022) or ICC criteria, or with MDS/AML as defined by ICC (with 10%-20% blasts in the bone marrow)
• Age ≥ 14 years, male or female.
• Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0-2.

• Meet the following laboratory requirements (tests must be performed within 7 days prior to treatment):

  i. Total bilirubin ≤ 1.5 times the upper limit of normal (ULN) for the corresponding age group.

ii. AST and ALT ≤ 2.5 times ULN for the corresponding age group. iii. Serum creatinine < 1.5 times ULN for the corresponding age group. iv. Cardiac enzymes < 2 times ULN for the corresponding age group. v. Left ventricular ejection fraction (LVEF) within the normal range as measured by echocardiography (ECHO).

Exclusion Criteria:

• Acute promyelocytic leukemia with PML::RARA fusion gene.
• Acute myeloid leukemia with RUNX1::RUNX1T1 fusion gene.
• Acute myeloid leukemia with BCR::ABL1 fusion gene.
• Previously treated patients (defined as having received prior induction chemotherapy for AML/MDS; prior use of cytoreductive agents like hydroxyurea is allowed).
• Concurrent active malignancy of other organs (requiring treatment).

• Active cardiac disease, defined as one or more of the following:

  i. History of uncontrolled or symptomatic angina. ii. Myocardial infarction within 6 months prior to study enrollment. iii. History of clinically significant arrhythmia requiring medication or causing severe symptoms.

iv. Uncontrolled or symptomatic congestive heart failure (> New York Heart Association [NYHA] Class 2).

• Active, uncontrolled infectious diseases (e.g., untreated tuberculosis, pulmonary aspergillosis).
• Any other condition that, in the opinion of the investigator, makes the patient unsuitable for study participation.

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: VAM Induction Regimen; Single-arm, phase I/II study evaluating venetoclax, azacitidine, and liposomal mitoxantrone (VAM) as induction in newly diagnosed AML patients fit for intensive chemotherapy. Patients receive 1-2 cycles of VAM induction, followed by 3 cycles of intermediate-dose cytarabine consolidation. Induction is dose-exploratory: first 10 patients receive venetoclax days 3-9; next 10 receive venetoclax days 3-14; subsequent 20 receive the selected regimen. High-risk or MRD+ patients may proceed to allogeneic HSCT.

Drug: Liposomal Mitoxantrone; Liposomal topoisomerase II inhibitor. 24 mg/m² IV on day 1 of each induction cycle.; Drug: Cytarabine; Antimetabolite. Consolidation: 2 g/m² (age <60) or 1 g/m² (age ≥60) q12h IV on days 1-3 for 3 cycles.; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation (HSCT); Recommended for high-risk or MRD+ patients after response.; Drug: Venetoclax; BCL-2 inhibitor. Oral. Induction: 100 mg day 1, 200 mg day 2, then 400 mg days 3-9 or 3-14.; Drug: Azacitidine; Hypomethylating agent. 75 mg/m²/day IV/SC on days 1-7 of induction.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Composite complete remission rate after induction	up to 42 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Relapse-free survival	Up to 5 years
Overall survival	Up to 5 years
30-day mortality	up to 30 days
Event-free survival	Up to 2 years
MRD negativity rate by flow cytometry and molecular methods (PCR/NGS) after 1 and 2 induction cycles	At the end of the first and second induction cycles
60-day mortality	up to 60 days

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2026
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): March 1, 2029

Study Registration Dates

• First Submitted: February 26, 2026
• First Submitted That Met QC Criteria: March 19, 2026
• First Posted (Actual): March 24, 2026

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Arabinonucleosides; Cytarabine; Azacitidine; venetoclax
• Other Study ID Numbers: IIT2026021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No