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

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

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.

Study Overview

• Status: Completed
• Conditions: Refractory Acute Myeloid Leukemia; Relapsed Acute Myeloid Leukemia; Gene Abnormality; Cytogenetic Abnormality
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Actual): 231

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Department of Hematology,Nanfang Hospital, Southern Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Cases included in this study were from 3 previous studies of our study group, including 1 exploratory and 2 prospective studies.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Nanfang Hospital of Southern Medical University
• Collaborators: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University; First People's Hospital of Chenzhou; Shenzhen Second People's Hospital; Peking University Shenzhen Hospital; The Seventh Affiliated Hospital of Sun Yat-sen University; Southern Medical University, China; Zhongshan People's Hospital, Guangdong, China; First Affiliated Hospital of Guangxi Medical University; Shenzhen Hospital of Southern Medical University
• Investigators: Principal Investigator: Liu Qifa, MD, Nanfang Hospital of Southern Medical University

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2018
• Primary Completion (Actual): May 31, 2022
• Study Completion (Actual): May 31, 2022

Study Registration Dates

• First Submitted: July 3, 2022
• First Submitted That Met QC Criteria: July 8, 2022
• First Posted (Actual): July 13, 2022

Study Record Updates

• Last Update Posted (Actual): July 13, 2022
• Last Update Submitted That Met QC Criteria: July 8, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Venetoclax; Acute myeloid leukemia; Homoharringtonine; Relapsed/refractory; Gene mutation
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Genetic Diseases, Inborn; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Congenital Abnormalities; Chromosome Disorders; Chromosome Aberrations
• Other Study ID Numbers: VAH-AML-2022

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No