Venetoclax, Azacitidine, and Mitoxantrone Hydrochloride Liposome Versus Idarubicin and Cytarabine in Newly Diagnosed AML

Phase 3Not Yet RecruitingNCT07486479

The First Affiliated Hospital of Soochow University204 enrolled

Overview

This study aims to evaluate the efficacy and safety of venetoclax combined with azacitidine and mitoxantrone hydrochloride liposome (MVA) versus idarubicin combined with cytarabine (IA) in the treatment of newly diagnosed AML.

For adult patients with newly diagnosed acute myeloid leukemia (AML) who are eligible for intensive chemotherapy, the standard intensive induction regimen remains anthracycline combined with cytarabine. However, the efficacy of traditional intensive chemotherapy is limited in high-risk AML and is associated with significant myelosuppression and infection risk, underscoring the need for novel therapeutic strategies. This study was therefore designed as a prospective, multicenter, randomized controlled trial. The study plans to enroll 204 adults with newly diagnosed AML. Participants will be randomized in a 2:1 ratio to receive induction therapy with either: 1) venetoclax, azacitidine, and mitoxantrone hydrochloride liposome (MVA), or 2) idarubicin and cytarabine (IA). The primary endpoint is the composite complete remission (CRc) rate following one cycle of induction therapy.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

204

Conditions

Acute Myeloid Leukemia (AML)

Interventions

Mitoxantrone Hydrochloride LiposomeDRUG

Mitoxantrone Hydrochloride Liposome: 24 mg/m², administered by intravenous drip (ivgtt) on day 1

VenetoclaxDRUG

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

AzacitidineDRUG

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 1\. The patient fully understands the study, voluntarily participates, and has signed the informed consent form (ICF). 2\. Aged 18 to 65 years, any gender. 3. Newly diagnosed with AML according to the 2022 WHO classification. 4. Eligible for intensive chemotherapy as determined by the investigator. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 6. Life expectancy ≥ 3 months. 7. Adequate liver and renal function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × upper limit of normal (ULN) (≤ 5 × ULN for patients with hepatic involvement); total bilirubin ≤ 1.5 × ULN (≤ 3 × ULN for patients with hepatic involvement); serum creatinine ≤ 1.5 × ULN. Exclusion Criteria: * Patients who meet any of the following criteria will be excluded from the study: 1. Any of the following conditions: 1. Acute promyelocytic leukemia (APL); 2. Central nervous system leukemia (CNSL); 3. AML secondary to chemotherapy/radiotherapy for other malignancies or antecedent hematological disorders (e.g., MDS, MPN, CML); 2. Prior treatment with hypomethylating agents (HMA) or venetoclax; 3. Prior anti-AML therapy (except for leukocytosis management such as hydroxyurea or leukapheresis); 4. History of other malignancies within the past 5 years (except for cured basal cell carcinoma of the skin, carcinoma in situ of the cervix, or other malignancies that have been effectively controlled without treatment in the past five years); 5. Inability to take oral medication or malabsorption syndrome; 6. Cardiac function or disease meeting any of the following criteria: 1. Long QTc syndrome or QTc interval \> 480 ms; 2. Complete left bundle branch block, second- or third-degree atrioventricular block; 3. Severe, uncontrolled arrhythmias requiring medication; 4. New York Heart Association (NYHA) Class ≥ II; 5. Left ventricular ejection fraction (LVEF) \< 50%; 6. History of myocardial infarction, unstable angina, severe unstable ventricular arrhythmia, or any other significant arrhythmia requiring treatment, clinically significant pericardial disease within 6 months prior to enrollment, or ECG evidence of acute ischemia or active conduction system abnormalities. 7. Uncontrolled systemic illnesses (e.g., active infection, uncontrolled hypertension, diabetes); 8. Human Immunodeficiency Virus (HIV) infection (HIV antibody positive); 9. Active Hepatitis B or C infection (Hepatitis B: HBsAg or HBcAb positive, with HBV-DNA \> 1×10³ copies/mL; Hepatitis C: HCV-Ab positive, with HCV-RNA \> 1×10³ copies/mL); 10. Known history of immediate or delayed hypersensitivity reaction to drugs of the same class or excipients of the investigational product; 11. Significant neurological or psychiatric history; 12. Pregnant or lactating women; 13. Patients considered by the investigator to be unsuitable for participation in this study.

Locations (21)

The First Affiliated Hospital of Anhui Medical University

Hefei, Anhui, China

Outcomes

Primary Outcomes

Composite Complete Remission(CRc) rate after one cycle of induction therapy

Complete remission plus complete remission with partial hematologic recovery plus complete remission with incomplete hematologic recovery (CR+CRh+CRi). Response is assessed according to the the European LeukemiaNet (ELN) 2022 criteria.

Time frame: At the end of the first treatment cycle (Day 28 ± 7), each cycle is 28 days).

Secondary Outcomes

Measurable residual disease (MRD) negativity rate (by flow cytometry and molecular testing) among patients who achieved CRc after induction therapy

Percentage of participants who achieve a CRc MRD- as defined by investigators based on ELN 2022 criteria.

Time frame: At the end of each cycle (Day 28 ± 7), each cycle is 28 days, up to 2 cycles.

Overall response rate(ORR) to induction therapy

CRc+morphologic leukemia-free state (MLFS)+partial remission (PR). Response is assessed according to the the European LeukemiaNet (ELN) 2022 criteria.

Time frame: At the end of each cycle (Day 28 ± 7), each cycle is 28 days, up to 2 cycles

Time to CRc

Defined as the time from day 1 of the treatment until the patient achieves CRc. Response is assessed according to the the European LeukemiaNet (ELN) 2022 criteria.

Time frame: Within 100 days from day 1 of treatment.

1-year relapsed-free survival (RFS) rate

Defined only for patients achieving CRc. Measured from the date of achievement of remission until the date of hematologic relapse or death from any cause.

Time frame: up to 1 years after the date of the last enrolled participants

1-year leukemia-free survival (LFS) rate

Central Contacts

Xiaowen Tang

CONTACT

0512-67780103 tangxiaowen@suda.edu.cn

Data from ClinicalTrials.gov

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