Venetoclax, Azacitidine and Liposomal Mitoxantrone for Newly Diagnosed AML

A 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 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.

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.