Venetoclax, Azacitidine and Liposomal Mitoxantrone for Newly Diagnosed AML

Institute of Hematology & Blood Diseases Hospital, China

Status: Enrolling

Conditions: AML

Treatments: Drug: Azacitidine; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation (HSCT); Drug: Cytarabine; Drug: Liposomal Mitoxantrone; Drug: Venetoclax

Study type: Interventional

Funder types: Other

Identifiers

NCT07490288

IIT2026021

Details and patient eligibility

About

This is a 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 patients with newly diagnosed Acute Myeloid Leukemia (AML) who are eligible for intensive chemotherapy.

The study plans to enroll 27 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.

Enrollment: 27 estimated patients

Sex: All

Ages: 14 to 100 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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27 participants in 1 patient group

VAM Induction Regimen

Experimental group

Description:

Single-arm 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. High-risk or MRD+ patients may proceed to allogeneic HSCT.

Treatment:

Drug: Venetoclax

Drug: Liposomal Mitoxantrone

Drug: Cytarabine

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Drug: Azacitidine