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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Acute Myeloid Leukemia (AML); Lisaftoclax
• Intervention / Treatment: Drug: Lisaftoclax+daunorubicin+cytarabine; Drug: Lisaftoclax+homoharringtonine+cytarabine+aclarubicin; Drug: Lisaftoclax+ cytarabine; Drug: Lisaftoclax+azacitidine or azacitidine; Drug: Lisaftoclax+azacitidine

• Study Type: Interventional
• Enrollment (Estimated): 450
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • The First Affiliated Hospital of Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Lisaftoclax+Daunorubicin+Cytarabine; Participants received induction therapy with lisaftoclax, daunorubicin, and cytarabine. Patients with partial response (PR) or >60% reduction in bone marrow blasts were allowed to receive one additional induction cycle. Patients achieving complete response received consolidation therapy with lisaftoclax and intermediate-dose cytarabine for 3 cycles. For maintenance therapy, patients were classified as post-transplant or non-transplant. Post-transplant patients were randomized 1:1 to receive either lisaftoclax plus azacitidine or azacitidine alone. Non-transplant patients received lisaftoclax in combination with azacitidine. Maintenance therapy was administered for up to 1 year or 10 cycles, whichever occurred first, or until the occurrence of grade ≥4 hematologic toxicity.	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).; Other Names: Induction chemotherapy; Drug: Lisaftoclax+ cytarabine; Lisaftoclax (600 mg, orally, D1-7) + intermediate-dose cytarabine (2 g/m², q12h, D1-3) for 3 cycles; Other Names: Consolidation treatment; 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, D1-7) in combination with azacitidine (50 mg/m², D1-7) for up to 1 year or 10 cycles, whichever occurred first.; Other Names: Maintenance treatment
Experimental: Arm B: Lisaftoclax+homoharringtonine+cytarabine+aclarubicin; Participants received induction therapy with lisaftoclax, homoharringtonine, cytarabine, and aclarubicin. Patients with partial response (PR) or >60% reduction in bone marrow blasts were allowed to receive one additional induction cycle. Patients achieving complete response received consolidation therapy with lisaftoclax and intermediate-dose cytarabine for 3 cycles. For maintenance therapy, patients were stratified according to transplantation status (post-transplant or non-transplant). Post-transplant patients were randomized 1:1 to receive either combination therapy or azacitidine monotherapy. Non-transplant patients received combination maintenance therapy. All maintenance therapies were administered for up to 1 year or 10 cycles, whichever occurred first, or until the occurrence of grade ≥4 hematologic toxicity, and were interrupted until recovery to grade ≤2.	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).; Other Names: Induction chemotherapy; Drug: Lisaftoclax+ cytarabine; Lisaftoclax (600 mg, orally, D1-7) + intermediate-dose cytarabine (2 g/m², q12h, D1-3) for 3 cycles; Other Names: Consolidation treatment; 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, D1-7) in combination with azacitidine (50 mg/m², D1-7) for up to 1 year or 10 cycles, whichever occurred first.; Other Names: Maintenance treatment
Experimental: Arm C:Lisaftoclax+ azacitidine; Participants received induction therapy with lisaftoclax in combination with azacitidine. Patients with partial response (PR) or >60% reduction in bone marrow blasts were allowed to receive one additional induction cycle. Patients achieving complete response received consolidation therapy with lisaftoclax and intermediate-dose cytarabine for 3 cycles. For maintenance therapy, patients were stratified according to transplantation status (post-transplant or non-transplant). Post-transplant patients were randomized 1:1 to receive either combination therapy or azacitidine monotherapy. Non-transplant patients received combination maintenance therapy. All maintenance therapies were administered for up to 1 year or 10 cycles, whichever occurred first, or until the occurrence of grade ≥4 hematologic toxicity, and were interrupted until recovery to grade ≤2.	Drug: Lisaftoclax+ cytarabine; Lisaftoclax (600 mg, orally, D1-7) + intermediate-dose cytarabine (2 g/m², q12h, D1-3) for 3 cycles; Other Names: Consolidation treatment; 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, D1-7) in combination with azacitidine (50 mg/m², D1-7) for up to 1 year or 10 cycles, whichever occurred first.; Other Names: Maintenance treatment; Drug: Lisaftoclax+azacitidine; Lisaftoclax (200 mg, orally, D1; 400 mg, orally, D2; 600 mg, orally, qd, D3-28) + azacitidine (75 mg/m², D1-7); Other Names: Induction chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year overall survival rate (OS)	defined as the proportion of patients who were still alive from the time of randomization for the last patient until 24 months later	from randomization up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year event-free survival (EFS) rate	defined as the proportion of patients remaining free of treatment failure, hematologic relapse, MRD relapse, or death within 2 years after randomization.	from randomization up to 2 years after randomization
2-year relapse-free survival (RFS) rate	defined as the proportion of patients who achieved complete response (CR) or complete remission with incomplete hematologic recovery (CRi) and remained alive without disease relapse within 2 years after achieving response.	from the date of complete remission (CR/CRi) up to 2 years after achieving response
Safety and Tolerability	defined as the number of participants with adverse events and serious adverse events as assessed by NCI CTCAE v5.0	up to 24 months
Complete Response (CR) rate after 1/2 treatment cycles	defined as the proportion of patients achieving complete response (CR) after the first or second cycle of induction chemotherapy.	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	defined as the proportion of patients achieving CRc after the first or second cycle of induction chemotherapy.	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	defined as the the proportion of patients with negative minimal residual disease (MRD) among patients who achieve complete remission after 1-2 cycles of induction chemotherapy	At the end of Cycle 1 or Cycle 2 of induction chemotherapy (each cycle is 28 days)

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: May 27, 2026
• First Submitted That Met QC Criteria: June 11, 2026
• First Posted (Actual): June 16, 2026

Study Record Updates

• Last Update Posted (Actual): June 16, 2026
• Last Update Submitted That Met QC Criteria: June 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Acuate myeloid leukemia, Lisaftoclax
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics; Drug Therapy; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Remission Induction; Azacitidine; Induction Chemotherapy; Opiate Substitution Treatment
• Other Study ID Numbers: CN-ZY-26-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No