Cytogenetic Abnormality, Gene Abnormality, Refractory Acute Myeloid Leukemia, Relapsed Acute Myeloid Leukemia
Conditions
Keywords
Acute myeloid leukemia, Relapsed/refractory, Gene mutation, Venetoclax, Homoharringtonine
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.
Interventions
DRUGVAH 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.
DRUGVEN+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.
Sponsors
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Zhongshan People's Hospital, Guangdong, China
Shenzhen Hospital of Southern Medical University
Peking University Shenzhen Hospital
Shenzhen Second People's Hospital
The Seventh Affiliated Hospital of Sun Yat-sen University
Southern Medical University, China
First People's Hospital of Chenzhou
First Affiliated Hospital of Guangxi Medical University
Nanfang Hospital, Southern Medical University
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CR/CRi | At the end of Cycle 2 (each cycle is 28 days) | Complete remission and CR with incomplete count recovery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
China
Outcome results
None listed