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

Official title

A Prospective, Multicenter, Randomized Controlled Clinical Study of Venetoclax Combined With Azacitidine and Mitoxantrone Hydrochloride Liposome Versus Idarubicin Combined With Cytarabine "3+7" in the Treatment of Newly Diagnosed AML

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.

Detailed description

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.

Interventions

• Drug Mitoxantrone Hydrochloride Liposome
  Mitoxantrone Hydrochloride Liposome: 24 mg/m², administered by intravenous drip (ivgtt) on day 1
• Drug Venetoclax
  Venetoclax: 100 mg on day 1, 200 mg on day 2, and 400 mg on days 3-9, administered orally (po)
• Drug Azacitidine
  Azacitidine: 75 mg/m², administered subcutaneously (sc) on days 1-7
• Drug Idarubicin
  Idarubicin: 12 mg/m², administered by intravenous drip (ivgtt) on days 1-3
• Drug Cytarabine
  Cytarabine: 100 mg/m², administered by intravenous drip (ivgtt) on days 1-7

Primary outcome measures

• Composite Complete Remission(CRc) rate after one cycle of induction therapy [Time frame: At the end of the first treatment cycle (Day 28 ± 7), each cycle is 28 days).]

Secondary outcome measures (11)

• Measurable residual disease (MRD) negativity rate (by flow cytometry and molecular testing) among patients who achieved CRc after induction therapy [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 [Time frame: At the end of each cycle (Day 28 ± 7), each cycle is 28 days, up to 2 cycles]
• Time to CRc [Time frame: Within 100 days from day 1 of treatment.]
• 1-year relapsed-free survival (RFS) rate [Time frame: up to 1 years after the date of the last enrolled participants]
• 1-year leukemia-free survival (LFS) rate [Time frame: up to 1 years after the date of the last enrolled participants]
• 1-year overall survival (OS) rate [Time frame: up to 1 years after the date of the last enrolled participants]
• Incidence of treatment-emergent adverse events, transfusion volume and time to hematologic recovery [Time frame: From day 1 of treatment to 28(±7) days after the last dose]
• Change in Health-Related Quality of Life Assessed by EQ-5D-5L [Time frame: up to 1 years after the date of the last enrolled participants]
• Change in Cancer-Specific Quality of Life Assessed by EORTC QLQ-C30 [Time frame: up to 1 years after the date of the last enrolled participants]
• Total Direct Medical Costs [Time frame: up to 1 year after the date of the last enrolled participant]
• Quality-Adjusted Life Years (QALYs) [Time frame: up to 1 year after the date of the last enrolled participant]

Eligibility criteria

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:

• Any of the following conditions:

• Acute promyelocytic leukemia (APL);
• Central nervous system leukemia (CNSL);
• AML secondary to chemotherapy/radiotherapy for other malignancies or antecedent hematological disorders (e.g., MDS, MPN, CML);
• Prior treatment with hypomethylating agents (HMA) or venetoclax;
• Prior anti-AML therapy (except for leukocytosis management such as hydroxyurea or leukapheresis);
• 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);
• Inability to take oral medication or malabsorption syndrome;
• Cardiac function or disease meeting any of the following criteria:

• Long QTc syndrome or QTc interval > 480 ms;
• Complete left bundle branch block, second- or third-degree atrioventricular block;
• Severe, uncontrolled arrhythmias requiring medication;
• New York Heart Association (NYHA) Class ≥ II;
• Left ventricular ejection fraction (LVEF) < 50%;
• 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.
• Uncontrolled systemic illnesses (e.g., active infection, uncontrolled hypertension, diabetes);
• Human Immunodeficiency Virus (HIV) infection (HIV antibody positive);
• 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);
• Known history of immediate or delayed hypersensitivity reaction to drugs of the same class or excipients of the investigational product;
• Significant neurological or psychiatric history;
• Pregnant or lactating women;
• Patients considered by the investigator to be unsuitable for participation in this study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 21 centers

• The First Affiliated Hospital of Anhui Medical University — Hefei
• The First Affiliated Hospital of Henan University of Science and Technology — Luoyang
• Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan
• Renmin Hospital of Wuhan University — Wuhan
• Changzhou First People's Hospital — Changzhou
• Huai'an Second People's Hospital — Huai'an
• Jingjiang People's Hospital — Jingjiang
• The First People's Hospital Of Lianyungang — Lianyungang
• … and 13 more centers

Identifiers

NCT: NCT07486479 · CSPC-DED-AML-K23

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗