Influence of Molecular Abnormalities on Response of VAH vs. VEN+HMA in RR-AML

Study Overview
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Brief Summary
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The aim of this study is to reveal the influence of gene mutations on the treatment response of the regimen of HHT combined with Venetoclax plus AZA versus venetoclax plus HMA in the salvage therapy of RR-AML.

Detailed Description
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Venetoclax-based regimens have heen used in the salvage therapy of relapsed/resfractory (RR) acute myeloid leukemia (AML). More and more studies have shown that molecular abnormalities and venetoclax combined regimens significantly impact the response of venetoclax-based therapy. Our exploratory study revealed that venetoclax plus azacytidine combined with homoharringtonine (VAH) had remarkably higher response than venetoclax plus hypomethylating agents (HMA) in RR-AML. Yet the influence of molecular abnormalities on the response of VAH regimen remains unknown.

Official Title
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Influence of Molecular Abnormalities on Treatment Response of the Regimen of Venetoclax Plus Azacytidine Combined With Homoharringtonine Versus Venetoclax Plus Hypomethylating Agents (HMA) in Relapsed/Refractory Acute Myeloid Leukemia

Conditions
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Relapsed Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia, Gene Abnormality, Cytogenetic Abnormality

Intervention / Treatment
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* Drug: VAH regimen
* Drug: VEN+HMA regimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: RR-AML Patients must have been treated for at least one cycle of VEN-based regimen and finished outcome assessment. Exclusion Criteria: Acute promyelocytic leukemia (AML subtype M3) Previous exposure to the treatment of VEN-based regimen Cardiac dysfunction (particularly congestive heart failure, unstable coronary artery disease and serious cardiac ventricular arrhythmias requiring antiarrhythmic therapy) Respiratory failure (PaO2 ≤60mmHg) Hepatic abnormalities (total bilirubin ≥2 times the upper limit of normal [ULN], alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2 times the ULN) Renal dysfunction (creatinine ≥2 times the ULN or creatinine clearance rate < 30 mL/min) ECOG performance status 3, 4 or 5 Substantial history of neurological, psychiatric, endocrine, metabolic, immunological, or any other medical condition not suitable for the trial (investigators' decision) Active acute or chronic graft-versus-host disease (GVHD). Active acute GVHD or chronic GVHD is defined as GVHD requiring either at least 1 mg/kg per day of prednisone (or equivalent) or treatment beyond systemic corticosteroids. Patients with pregnancy Uncontrolled active infection Clinically significant coagulation abnormalities

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| VAH group<br>Patients assigned to this group received one to two cycles of VAH regimen as salvage therapy of RR-AML. | Drug: VAH regimen<br>* VEN was prescribed as 100mg day 1, 200mg day 2, 400mg day 3-14; AZA was used at the dose of 75 mg/m2, day 1-7; HHT was given at a dose of 1mg/m2, day 1-7. The dose of VEN was reduced to 100mg/d if co-administered with posaconazole or voriconazole.<br>|
| VEN+HMA group<br>Patients assigned to this group received one to two cycles of venetoclax plus HMA regimen as salvage therapy of RR-AML. | Drug: VEN+HMA regimen<br>* VEN was prescribed as 100mg day 1, 200mg day 2, 400mg day 3-28; AZA was used at the dose of 75 mg/m2, day 1-7 or DEC 20mg/m2 day 1-5. The dose of VEN was reduced to 100mg/d if co-administered with posaconazole or voriconazole.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CR/CRi | Complete remission and CR with incomplete count recovery | At the end of Cycle 2 (each cycle is 28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRD negative | MRD was detected with FCM and defined negative as a ratio < 0.1% | At the end of Cycle 2 (each cycle is 28 days) | 
| Overall response | Overall response included CR/CRi, MLFS and PR. | At the end of Cycle 2 (each cycle is 28 days) | 
| Overall survival | The time from enrolling to death or the last follow up | 2 years | 
| Event-free survival | The time from enrolling to no response, relapse, death or the last follow up | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute myeloid leukemia, Relapsed/refractory, Gene mutation, Venetoclax, Homoharringtonine