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

Sponsor

Nanfang Hospital of Southern Medical University (Other)

Overall Status

Completed

CT.gov ID

NCT05456048

Collaborator

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University (Other), Zhongshan People's Hospital, Guangdong, China (Other), Shenzhen Hospital of Southern Medical University (Other), Peking University Shenzhen Hospital (Other), Shenzhen Second People's Hospital (Other), The Seventh Affiliated Hospital of Sun Yat-sen University (Other), Southern Medical University, China (Other), First People's Hospital of Chenzhou (Other), First Affiliated Hospital of Guangxi Medical University (Other)

231

Enrollment

Location

41.9

Actual Duration (Months)

5.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Relapsed Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia Gene Abnormality Cytogenetic Abnormality	Drug: VAH regimen Drug: VEN+HMA regimen

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 Design

Study Type:

Observational

Actual Enrollment :

231 participants

Observational Model:

Cohort

Time Perspective:

Retrospective

Official Title:

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

Actual Study Start Date :

Dec 3, 2018

Actual Primary Completion Date :

May 31, 2022

Actual Study Completion Date :

May 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
VAH group Patients assigned to this group received one to two cycles of VAH regimen as salvage therapy of RR-AML.	Drug: VAH regimen 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.
VEN+HMA group 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 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.

Arm

Intervention/Treatment

VAH group

Patients assigned to this group received one to two cycles of VAH regimen as salvage therapy of RR-AML.

Drug: VAH regimen

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.

VEN+HMA group

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

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.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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