Comparing the Efficacy of LDA, LHAA, and LA Regimens in Young Adults With Intermediate- and High-Risk Acute Myeloid Leukemia Eligible for Intensive Chemotherapy

A Multicenter, Prospective, Randomized Controlled Clinical Study Comparing the Efficacy of LDA, LHAA, and LA Regimens in Young Adults With Intermediate- and High-Risk Acute Myeloid Leukemia Eligible for Intensive Chemotherapy

This is a phase II/III, multicenter, randomized, three-arm, open-label, parallel controlled trial. The primary objective of this study is to compare the 2-years OS rate of the LDA, LHAA, and LA regimens in newly diagnosed patients with intermediate- and high-risk acute myeloid leukemia who are eligible for intensive chemotherapy.

Inclusion Criteria:

1. Newly diagnosed acute myeloid leukemia (AML) confirmed according to the World Health Organization (WHO) classification;
2. Classified as intermediate- or adverse-risk AML based on the European LeukemiaNet (ELN) 2022 genetic risk stratification (see Appendix Table 1);
3. Age 15-65 years;
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
5. Adequate hepatic and renal function: total bilirubin ≤2 mg/dL (35 μmol/L); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2× the upper limit of normal; serum creatinine ≤177 μmol/L;
6. Normal cardiac function, defined as left ventricular ejection fraction (LVEF) >50%;
7. Life expectancy ≥3 months;
8. Signed written informed consent by the patient or their legally authorized representative prior to study enrollment.

Exclusion Criteria:

1. Acute promyelocytic leukemia;
2. Central nervous system involvement by leukemia;
3. History of other malignancies within the past 5 years;
4. Positive for human immunodeficiency virus (HIV);
5. Presence of any other serious medical condition that may limit study participation, including advanced infections, uncontrolled diabetes mellitus, severe cardiac insufficiency, or angina;
6. Ineligible for intensive chemotherapy due to poor general condition;
7. Pregnant or breastfeeding women;
8. Inability to understand or comply with the study protocol;
9. Inability to take oral medication or presence of malabsorption syndrome;
10. Prior treatment with B-cell lymphoma 2 (BCL-2) inhibitors or hypomethylating agents, or current participation in any other investigational drug study;
11. Inability or unwillingness to provide written informed consent.