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

Completed

• Conditions: Relapsed Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Cytogenetic Abnormality; Gene Abnormality
• Interventions: Drug: VAH regimen; Drug: VEN+HMA regimen

• Registration Number: NCT05456048
• Lead Sponsor: Nanfang Hospital, Southern Medical University

Brief Summary

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

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.

Study Timeline

• Study Start: 2018-12-03
• Primary Completion: 2022-05-31
• Study Completion: 2022-05-31
• Status Verified: 2022-07
• Study First Submitted: 2022-07-03
• Study First Submitted QC: 2022-07-08
• Last Update Submitted: 2022-07-08
• Study First Posted: 2022-07-13
• Last Update Posted: 2022-07-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 231

Inclusion Criteria

1. RR-AML
2. Patients must have been treated for at least one cycle of VEN-based regimen and finished outcome assessment.

Exclusion Criteria

1. Acute promyelocytic leukemia (AML subtype M3)
2. Previous exposure to the treatment of VEN-based regimen
3. Cardiac dysfunction (particularly congestive heart failure, unstable coronary artery disease and serious cardiac ventricular arrhythmias requiring antiarrhythmic therapy)
4. Respiratory failure (PaO2 ≤60mmHg)
5. Hepatic abnormalities (total bilirubin ≥2 times the upper limit of normal [ULN], alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2 times the ULN)
6. Renal dysfunction (creatinine ≥2 times the ULN or creatinine clearance rate < 30 mL/min)
7. ECOG performance status 3, 4 or 5
8. Substantial history of neurological, psychiatric, endocrine, metabolic, immunological, or any other medical condition not suitable for the trial (investigators' decision)
9. 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.
10. Patients with pregnancy
11. Uncontrolled active infection
12. Clinically significant coagulation abnormalities

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
VAH group	VAH regimen	Patients assigned to this group received one to two cycles of VAH regimen as salvage therapy of RR-AML.
VEN+HMA group	VEN+HMA regimen	Patients assigned to this group received one to two cycles of venetoclax plus HMA regimen as salvage therapy of RR-AML.

Primary Outcome Measures

Name	Time	Method
CR/CRi	At the end of Cycle 2 (each cycle is 28 days)	Complete remission and CR with incomplete count recovery

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Department of Hematology,Nanfang Hospital, Southern Medical University; 🇨🇳 Guangzhou, Guangdong, China