Clinical trial NCT05456048: Influence of Molecular Abnormalities on Response of VAH vs. VEN+HMA in RR-AML
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Relapsed Acute Myeloid Leukemia
Refractory Acute Myeloid Leukemia
Gene Abnormality
Cytogenetic Abnormality
Keywords: Acute myeloid leukemia
Relapsed/refractory
Gene mutation
Venetoclax
Homoharringtonine
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
Collaborators: name: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Zhongshan People's Hospital, Guangdong, China
name: Shenzhen Hospital of Southern Medical University
name: Peking University Shenzhen Hospital
name: Shenzhen Second People's Hospital
name: The Seventh Affiliated Hospital of Sun Yat-sen University
name: Southern Medical University, China
name: First People's Hospital of Chenzhou
name: First Affiliated Hospital of Guangxi Medical University
First posted: 2022-07-13
Enrollment: 231
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: CR/CRi
timeFrame: At the end of Cycle 2 (each cycle is 28 days)
Secondary outcomes:
measure: MRD negative
timeFrame: At the end of Cycle 2 (each cycle is 28 days)
measure: Overall response
timeFrame: At the end of Cycle 2 (each cycle is 28 days)
measure: Overall survival
timeFrame: 2 years
measure: Event-free survival
timeFrame: 2 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Department of Hematology,Nanfang Hospital, Southern Medical University
state: Guangdong
Study officials:
affiliation: Nanfang Hospital, Southern Medical University
name: Liu Qifa, MD
role: PRINCIPAL_INVESTIGATOR
References: