Acute Myeloid Leukemia (AML)
Conditions
Keywords
Acute myeloid leukemia, mitoxantrone hydrochloride liposome, Venetoclax, Azacitidine, Idarubicin, Cytarabine, Randomized Controlled Trial
Brief summary
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
DRUGMitoxantrone Hydrochloride Liposome
Mitoxantrone Hydrochloride Liposome: 24 mg/m², administered by intravenous drip (ivgtt) on day 1
DRUGVenetoclax
Venetoclax: 100 mg on day 1, 200 mg on day 2, and 400 mg on days 3-9, administered orally (po)
DRUGAzacitidine
Azacitidine: 75 mg/m², administered subcutaneously (sc) on days 1-7
DRUGIdarubicin
Idarubicin: 12 mg/m², administered by intravenous drip (ivgtt) on days 1-3
DRUGCytarabine
Cytarabine: 100 mg/m², administered by intravenous drip (ivgtt) on days 1-7
Sponsors
The First Affiliated Hospital of Soochow University
CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite Complete Remission(CRc) rate after one cycle of induction therapy | At the end of the first treatment cycle (Day 28 ± 7), each cycle is 28 days). | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measurable residual disease (MRD) negativity rate (by flow cytometry and molecular testing) among patients who achieved CRc after induction therapy | At the end of each cycle (Day 28 ± 7), each cycle is 28 days, up to 2 cycles. | Percentage of participants who achieve a CRc MRD- as defined by investigators based on ELN 2022 criteria. |
| Overall response rate(ORR) to induction therapy | At the end of each cycle (Day 28 ± 7), each cycle is 28 days, up to 2 cycles | CRc+morphologic leukemia-free state (MLFS)+partial remission (PR). Response is assessed according to the the European LeukemiaNet (ELN) 2022 criteria. |
| Time to CRc | Within 100 days from day 1 of treatment. | 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. |
| 1-year relapsed-free survival (RFS) rate | up to 1 years after the date of the last enrolled participants | 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. |
| 1-year leukemia-free survival (LFS) rate | up to 1 years after the date of the last enrolled participants | Defined only for patients achieving CRc. Measured from day 1 of treatment to the date of first documented leukemia relapse or death from any cause. |
| 1-year overall survival (OS) rate | up to 1 years after the date of the last enrolled participants | Defined for all patients in the study. Measured from day 1 of treatment to the date of death from any cause. |
| Incidence of treatment-emergent adverse events, transfusion volume and time to hematologic recovery | From day 1 of treatment to 28(±7) days after the last dose | Safety assessments included adverse events (graded by NCI CTCAE v5.0), the number of units of red blood cells and platelets transfused, time to neutrophil recovery to ≥0.5x10⁹/L, and time to platelet recovery to ≥20x10⁹/L. |
| Change in Health-Related Quality of Life Assessed by EQ-5D-5L | up to 1 years after the date of the last enrolled participants | EuroQol 5-Dimension 5-Level (EQ-5D-5L) is a standardized instrument for measuring generic health-related quality of life. It comprises a descriptive system (generating a health utility score for cost-utility analysis) and a Visual Analogue Scale (EQ VAS) recording the participant's self-rated health. Recommended assessment time points: Baseline, end of Cycle 1 induction therapy (Day 28 ± 7, assessable after completion of bone marrow aspiration), end of Cycle 2 induction therapy (Day 28 ± 7), end of consolidation therapy, first follow-up after transplantation, and follow-up after first relapse. |
| Change in Cancer-Specific Quality of Life Assessed by EORTC QLQ-C30 | up to 1 years after the date of the last enrolled participants | The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) is a cancer-specific instrument. It includes a Global Health Status/Quality of Life scale, five functional scales (physical, role, emotional, cognitive, social), and nine symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties). Recommended assessment time points: Baseline, end of Cycle 1 induction therapy (Day 28 ± 7, assessable after completion of bone marrow aspiration), end of Cycle 2 induction therapy (Day 28 ± 7), end of consolidation therapy, first follow-up after transplantation, and follow-up after first relapse. |
| Total Direct Medical Costs | up to 1 year after the date of the last enrolled participant | Total direct medical costs (including costs of study drugs, concomitant medications, hospitalization, outpatient visits, laboratory tests, and management of adverse events) incurred over the study period. Costs will be estimated based on patient-level resource utilization data collected during the trial and, if applicable, extrapolated using a long-term simulation model. Unit of Measure: Currency (CNY) |
| Quality-Adjusted Life Years (QALYs) | up to 1 year after the date of the last enrolled participant | Quality-adjusted life years gained, calculated by integrating survival data with health utility weights derived from the EQ-5D-5L questionnaire administered at specified time points during the trial. A long-term simulation model may be used to extrapolate QALYs beyond the observation period. Unit of Measure: Years |
Countries
China
Contacts
CONTACTXiaowen Tang
PRINCIPAL_INVESTIGATORDepei Wu
The First Affiliated Hospital of Soochow University
Outcome results
None listed