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

Refractory Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05456048
• Other study ID #: VAH-AML-2022
• Status: Completed
• Start date: December 3, 2018
• Est. completion date: May 31, 2022

Study information

• Verified date: July 2022
• Source: Nanfang Hospital of Southern Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 231
• Est. completion date: May 31, 2022
• Est. primary completion date: May 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Chromosome Aberrations
• Chromosome Disorders
• Congenital Abnormalities
• Cytogenetic Abnormality
• Gene Abnormality
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Refractory Acute Myeloid Leukemia
• Relapsed Acute Myeloid Leukemia

Intervention

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 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.

Locations

Country	Name	City	State
China	Department of Hematology,Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong

Sponsors (10)

Lead Sponsor

Collaborator

Nanfang Hospital of Southern Medical University

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

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CR/CRi	Complete remission and CR with incomplete count recovery	At the end of Cycle 2 (each cycle is 28 days)
Secondary	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)
Secondary	Overall response	Overall response included CR/CRi, MLFS and PR.	At the end of Cycle 2 (each cycle is 28 days)
Secondary	Overall survival	The time from enrolling to death or the last follow up	2 years
Secondary	Event-free survival	The time from enrolling to no response, relapse, death or the last follow up	2 years