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

NCT07651163 | Enrolling By Invitation Phase 2 DMC

• 1 other identifier: CN-ZY-26-02
• Study Type: interventional
• Target: 450
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Myeloid Leukemia (AML); Lisaftoclax

Keywords

Acuate myeloid leukemia, Lisaftoclax

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Complete Response (CR) rate after 1/2 treatment cycles

  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

  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

  At the end of Cycle 1 or Cycle 2 of induction chemotherapy (each cycle is 28 days)

• 2-year event-free survival (EFS) rate

  from randomization up to 2 years after randomization

• 2-year relapse-free survival (RFS) rate

  from the date of complete remission (CR/CRi) up to 2 years after achieving response

Study Arms (3)

Arm A: Lisaftoclax+Daunorubicin+Cytarabine

EXPERIMENTAL

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; Drug: Lisaftoclax+ cytarabine; Drug: Lisaftoclax+azacitidine or azacitidine

Arm B: Lisaftoclax+homoharringtonine+cytarabine+aclarubicin

EXPERIMENTAL

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; Drug: Lisaftoclax+ cytarabine; Drug: Lisaftoclax+azacitidine or azacitidine

Arm C:Lisaftoclax+ azacitidine

EXPERIMENTAL

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+azacitidine; Drug: Lisaftoclax+ cytarabine; Drug: Lisaftoclax+azacitidine or azacitidine

Interventions

Lisaftoclax+azacitidine DRUG

Lisaftoclax (200 mg, orally, D1; 400 mg, orally, D2; 600 mg, orally, qd, D3-28) + azacitidine (75 mg/m², D1-7)

Also known as: Induction chemotherapy

Arm C:Lisaftoclax+ azacitidine

Lisaftoclax+daunorubicin+cytarabine DRUG

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).

Also known as: Induction chemotherapy

Arm A: Lisaftoclax+Daunorubicin+Cytarabine

Lisaftoclax+homoharringtonine+cytarabine+aclarubicin DRUG

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).

Also known as: Induction chemotherapy

Arm B: Lisaftoclax+homoharringtonine+cytarabine+aclarubicin

Lisaftoclax+ cytarabine DRUG

Lisaftoclax (600 mg, orally, D1-7) + intermediate-dose cytarabine (2 g/m², q12h, D1-3) for 3 cycles

Also known as: Consolidation treatment

Arm A: Lisaftoclax+Daunorubicin+Cytarabine; Arm B: Lisaftoclax+homoharringtonine+cytarabine+aclarubicin; Arm C:Lisaftoclax+ azacitidine

Lisaftoclax+azacitidine or azacitidine DRUG

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.

Also known as: Maintenance treatment

Arm A: Lisaftoclax+Daunorubicin+Cytarabine; Arm B: Lisaftoclax+homoharringtonine+cytarabine+aclarubicin; Arm C:Lisaftoclax+ azacitidine

Eligibility Criteria

• Age: 15 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead

Study Sites (1)

The First Affiliated Hospital of Zhejiang University

Hangzhou, Zhejiang, 310000, China

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Induction Chemotherapy; Azacitidine; Opiate Substitution Treatment

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Drug Therapy; Therapeutics; Remission Induction; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 27, 2026
• First Posted: June 16, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: June 16, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)