Clinical trial · Interventional
Homoharringtonine, Lisaftoclax, and Azacitidine for AML After Venetoclax-Based Therapy Failure
A Multi-Center, Prospective, Open-Label, Single-Arm Study of Homoharringtonine Combined With Lisaftoclax and Azacitidine in Patients With Acute Myeloid Leukemia After Failure of Venetoclax-Based Therapy
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 11, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260911-000001
Summary
Brief summary (as posted)
Venetoclax (Ven) resistance is common in the treatment of acute myeloid leukemia (AML). Patients with Ven resistance have poor response and survival, except those with specific targeted therapy. Whether we could use new BCL-2 inhibitors to replace Ven and combine with the agents which have been shown to enhance the antilekeumia effect of BCL-2 inhibitors, to overcome Ven resistance? This is unknown up until now. This multi-center, prospective, open-label, single-arm study will evaluate the efficacy and safety of homoharringtonine combined with lisaftoclax and azacitidine (HLA) as salvage therapy for adults with AML after failure of a Ven-containing regimen. Ven treatment failure is defined as no response after at least two consecutive cycles of a Ven-containing regimen or relapse during continued, protocol-compliant Ven-based therapy after a prior response. The study plans to enroll 73 participants. The primary endpoint is the overall response rate after two treatment cycles. Secondary endpoints include complete remission (CR), CR with incomplete blood count recovery (CRi), measurable residual disease (MRD) negativity, survival and relapse, and treatment-related adverse events.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Acute Myeloid Leukemia (AML) | Acute Myeloid Leukemia | CURATED_BROADER | 0.80 |
Interventions
Interventions (3)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Azacitidine (AZA) | Drug | Azacitidine | ALIAS |
| homoharringtonine | Drug | Omacetaxine Mepesuccinate | ALIAS |
| Lisaftoclax (APG-2575) | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- HLA Regimen
- description
- Participants will receive homoharringtonine, lisaftoclax, and azacitidine in 28-day salvage-treatment cycles. One or two cycles will be administered according to treatment response and eligibility for allogeneic hematopoietic stem cell transplantation, as described in the protocol.
- interventionNames
- Drug: Lisaftoclax (APG-2575)
- Drug: homoharringtonine
- Drug: Azacitidine (AZA)
Primary outcomes (1)
- measure
- Overall Response Rate After Two Cycles of HLA Therapy
- timeFrame
- At the end of Cycle 2 (each cycle is 28 days; approximately Day 56)
- description
- The proportion of participants who achieve complete remission (CR), complete remission with incomplete hematologic recovery (CRi), partial remission (PR), or morphologic leukemia-free state (MLFS). CR is defined as bone marrow blasts \<5%, no peripheral blood blasts or extramedullary disease, neutrophils \>=1 x 10\^9/L, and platelets \>=100 x 10\^9/L. CRi is defined as meeting the CR criteria except for neutrophils \<1 x 10\^9/L and/or platelets \<100 x 10\^9/L. PR is defined as a \>60% reduction in bone marrow blasts with bone marrow blasts \<20%. MLFS is defined as bone marrow blasts \<5%, no peripheral blood blasts or extramedullary disease, without a requirement for blood-count recovery.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: 1. Diagnosis of acute myeloid leukemia according to the World Health Organization classification. 2. Age 18 years or older. 3. Failure after venetoclax exposure, defined as either no response after at least 2 consecutive cycles of a venetoclax-containing regimen or disease relapse during continued, protocol-compliant treatment with a venetoclax-containing regimen after a prior response. 4. Creatinine clearance of at least 30 mL/min. 5. Alanine aminotransferase less than 5 times the upper limit of normal and bilirubin less than 3 times the upper limit of normal. 6. Life expectancy of at least 3 months. 7. Able to receive oral lisaftoclax. 8. Able to understand and comply with protocol procedures and willing to provide written informed consent. Exclusion Criteria: 1. Acute promyelocytic leukemia. 2. Acute myeloid leukemia with central nervous system involvement. 3. Acute myeloid leukemia with FLT3, IDH1/2, or NPM1 mutations or MLL rearrangement for which could be treated with a corresponding targeted inhibitor. 4. Other clinically significant uncontrolled conditions, including but not limited to an uncontrolled or active systemic viral, bacterial, or fungal infection; chronic hepatitis B virus or hepatitis C virus infection requiring treatment; or a concurrent second malignancy requiring active treatment. 5. Known hypersensitivity to any study drug. 6. Active human immunodeficiency virus infection. 7. Pregnant or breastfeeding. 8. Any condition that, in the investigator's opinion, makes the patient unsuitable for enrollment.
References
Publications (0)
Data not yet available