Acute Myeloid Leukemia
Conditions
Keywords
Venetoclax, Azacitidine, Granulocyte colony-stimulating factor(G-CSF), Cytarabine, Aclarubicin
Brief summary
This study aims to assess the therapeutic efficacy and safety of venetoclax in combination with azacitidine and CAG(VA-CAG) as induction regimen in newly diagnosed young patients with acute myeloid leukemia(AML).
Detailed description
This is an open-label, multicenter, phase II clinical trial to assess the therapeutic efficacy and safety of venetoclax in combination with azacitidine (VA) and CAG (G-CSF priming, low dose cytarabine, and aclarubicin) as induction regimen in newly diagnosed patients with acute myeloid leukemia (AML). The combination of venetoclax and azacitidine is the standard therapy for elderly (\> 60 year old) patients with newly diagnosed AML who are not eligible for intensive chemotherapy. Previous studies have shown that venetoclax plus intense chemotherapy represent promising efficacy in de novo AML patients with high complete remission rates and good tolerance. The preliminary results suggest that venetoclax in combination with azacitidine and CAG are well tolerated and effective for newly diagnosed young patients with AML. Thus, this phase II clinical trial is going to further explore its efficacy and safety. It is expected that about 100 patients will take part in this trial.
Interventions
DRUGVenetoclax in combination with azacitidine and CAG
Induction: VA regimen： Drug: Venetoclax orally once daily (100 mg d1, 200 mg d2, 400 mg d3-21); Drug: Azacitidine 75 mg/m2 subcutaneously once daily on days 1-7. CAG regimen： Drug: Cytarabine 10mg/m2 subcutaneously q12h on days 1-7; Drug: Aclacinomycin 12-14mg/m2 on days 1,3,5,7; Drug: Granulocyte colony-stimulating factor 5ug/kg on days 0-8, discontinue if WBC \>20×10\^9/L； Consolidation: Drug: Cytarabine 3g/m2 q12h on days 1-3.
Sponsors
Hematology department of the 920th hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Patients ≥ 18 years old and ≤ 65 years old 2. Newly diagnosed as AML patients according to 2016 World Health Organization (WHO) classification; 3. Patients without receiving prior therapy for AML; 4. Eastern Cooperative Oncology Group (ECOG) Performance status score less than 3; 5. Liver function: Total bilirubin ≦2 upper limit of normal (ULN); aspartate aminotransferase (AST) ≦3 ULN; alanine aminotransferase (ALT)≦3 ULN 6. Renal function：Ccr（Creatinine Clearance Rate） ≧30 ml/min; Scr (serum creatinine) ≦2 ULN 7. Heart function: left ventricular ejection fraction ≧45% 8. Patients must participate in this clinical trial voluntarily and sign an informed consent form.
Exclusion criteria
1. Acute promyeloid leukemia； 2. AML with central nervous system (CNS) infiltration； 3. Patients have received prior hypomethylating agents (HMA) therapy for myelodysplastic syndrome (MDS) and progressed to AML； 4. Patients with a life expectancy \<3 months 5. Patients with uncontrolled active infection; 6. HIV infection; 7. Evidence of other clinically significant uncontrolled condition(s) including, but not limited to: a) Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment; b) An active second cancer that requires treatment within 6 months of study entry. 8. Female who are pregnant, breast feeding or childbearing potential. 9. Patients deemed unsuitable for enrollment by the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| CR rate | At the end of Cycle 1 of induction (each cycle is about 30 days) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | From the first day of induction until the starting day of the next cycle of therapy (up to 60 days） | Safety and tolerability analysis will be assessed by the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0. |
| Duration of remission | From the date of the first remission until the date of relapse (assessed up to 30 months) | DOR was defined as the period from the time to acquire CR until relapse |
| Minimal Residual Disease negative remission rate (MRD-negative rate) | After 1 cycle of induction (each cycle is about 30 days) | Percentage of participants who converted to MRD \< 10\^-3 by flow cytometry before initiation of consolidation therapy. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | From the first day of induction until the date of death from any cause, assessed up to 30 months | Overall Survival will be defined as the time from administration of the initial doses until death from any cause. |
| Relapse-free survival | From the first day of induction until the date of relapse or the date of death from any cause, assessed up to 30 months | Relapse-free survival will be defined as the time since date of CR until either relapse or death in remission. |
Countries
China
Outcome results
None listed