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

Official title

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

Overview

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.

Interventions

• Drug Lisaftoclax+daunorubicin+cytarabine
  Lisaftoclax (200 mg on D2, 400 mg on D3, and 600 mg qd on D4-8, orally) + daunorubicin (60 mg/m², iv, qd, D1-3) + cytarabine (100 mg/m², q12h, subcutaneous injection or iv infusion, D1-7).
• Drug Lisaftoclax+homoharringtonine+cytarabine+aclarubicin
  Lisaftoclax (200 mg on D2, 400 mg on D3, and 600 mg qd on D4-8, orally) + homoharringtonine (2 mg/m², qd, intramuscular injection or iv infusion, D1-5) + cytarabine (100 mg/m², q12h, subcutaneous injection or iv infusion, D1-5) + aclarubicin (12 mg/m², maximum 20 mg, iv, D1-5).
• Drug Lisaftoclax+azacitidine
  Lisaftoclax (200 mg, orally, D1; 400 mg, orally, D2; 600 mg, orally, qd, D3-28) + azacitidine (75 mg/m², D1-7)
• Drug Lisaftoclax+ cytarabine
  Lisaftoclax (600 mg, orally, D1-7) + intermediate-dose cytarabine (2 g/m², q12h, D1-3) for 3 cycles
• Drug Lisaftoclax+azacitidine or azacitidine
  Post-transplant maintenance therapy: patients were randomized 1:1 to receive either combination therapy or azacitidine monotherapy. The combination regimen consisted of lisaftoclax (400 mg, orally, D1-7) in combination with azacitidine (50 mg/m², D1-7) for up to 1 year or 10 cycles, whichever occurred first. Azacitidine monotherapy consisted of azacitidine (50 mg/m², D1-7) for up to 1 year or 10 cycles, whichever occurred first. Non-transplant maintenance therapy: lisaftoclax (400 mg, orally, D1

Primary outcome measures

• 2-year overall survival rate (OS) [Time frame: from randomization up to 2 years]

Secondary outcome measures (6)

• Complete Response (CR) rate after 1/2 treatment cycles [Time frame: At the end of Cycle 1 or Cycle 2 of induction chemotherapy (each cycle is 28 days)]
• Composite Complete Response (CRc) rate after 1/2 treatment cycles [Time frame: At the end of Cycle 1 or Cycle 2 of induction chemotherapy (each cycle is 28 days)]
• Minimal residual disease (MRD) negativity rate after 1-2 cycles of induction chemotherapy [Time frame: At the end of Cycle 1 or Cycle 2 of induction chemotherapy (each cycle is 28 days)]
• 2-year event-free survival (EFS) rate [Time frame: from randomization up to 2 years after randomization]
• 2-year relapse-free survival (RFS) rate [Time frame: from the date of complete remission (CR/CRi) up to 2 years after achieving response]
• Safety and Tolerability [Time frame: up to 24 months]

Eligibility criteria

Inclusion criteria

• Newly diagnosed acute myeloid leukemia (AML) confirmed according to the World Health Organization (WHO) classification;
• Classified as intermediate- or adverse-risk AML based on the European LeukemiaNet (ELN) 2022 genetic risk stratification (see Appendix Table 1);
• Age 15-65 years;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
• 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;
• Normal cardiac function, defined as left ventricular ejection fraction (LVEF) >50%;
• Life expectancy ≥3 months;
• Signed written informed consent by the patient or their legally authorized representative prior to study enrollment.

Exclusion criteria

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

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 · 1 center

• The First Affiliated Hospital of Zhejiang University — Hangzhou

Identifiers

NCT: NCT07651163 · CN-ZY-26-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗