AML (Acute Myelogenous Leukemia)
Conditions
Keywords
Acute myeloid leukemia, Venetoclax, Cytarabine, Consolidation, Measurable residual disease
Brief summary
This study intends to use a randomized controlled design to compare the MRD-negativw rate and related efficacy and safety of venetoclax combined with intermediate-dose cytarabine (IDAC) versus IDAC in the consolidation treatment of patients with AML after remission, providing high-quality evidence-based medical evidence for optimizing post-remission consolidation therapy for AML and improving patients' prognosis.
Detailed description
Studies have shown that venetoclax can significantly enhance the efficacy of intensive chemotherapy (IC) in the induction and salvage treatment of AML. However, there is still a lack of direct comparison of the efficacy and safety of venetoclax combined with intermediate-dose cytarabine (IDAC) with IDAC for consolidation in AML. In order to evaluate the benefit of venetoclax combined with IDAC, we plan to conduct a multicenter, prospective randomized controlled, phase 2 study to compare the efficacy and safety of venetoclax (d1-7, 400mg QD) combined with cytarabine (d1-3, 1.5g/㎡, q12h) versus cytarabine only for consolidation therapy in AML, aiming to fill the current evidence gap and provide scientific basis for improving deeper remission of AML and finally improve patients' long-term survival.
Interventions
DRUGVentoclax
Venetoclax 400mg per day from day 1 to day 7
DRUGCytarabine
Cytarabine 1.5g/m\^2 q12h from day 1 to day 3.
Sponsors
Guangdong Second Provincial General Hospital
Nanfang Hospital, Southern Medical University
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
First Affiliated Hospital of Guangxi Medical University
Guangzhou First People's Hospital
Dongguan People's Hospital
Zhongshan People's Hospital, Guangdong, China
Shunde Hospital, Sothen Medical University
Shenzhen Second People's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Age between 18 and 65 years, any gender; 2. Meet the WHO 2022 diagnostic criteria for acute myeloid leukemia (AML), and achieve complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) after induction therapy. CR is defined as bone marrow blasts ≤5%, absolute neutrophil count ≥1.0×10⁹/L, and platelets ≥100×10⁹/L; CRi is defined as bone marrow blasts ≤5%, absolute neutrophil count ≥0.5×10⁹/L, and platelets ≥50×10⁹/L; 3. Baseline MRD testing (using multiparameter flow cytometry, MFC) must be completed at enrollment. 4. Eastern Cooperative Oncology Group (ECOG) performance status score ≤2; 5. Major organ function is basically normal and meets the following requirements: ① Liver function: total bilirubin ≤1.5×ULN (except patients with liver metastasis or Gilbert's syndrome), ALT and AST ≤2.5×ULN; ② Kidney function: serum creatinine ≤1.5×ULN or creatinine clearance ≥60 ml/min; ③ Cardiac function: left ventricular ejection fraction (LVEF) ≥50%; 6. The patient or their legal representative signs a written informed consent form, agrees to comply with the study protocol, and completes the specified follow-up procedures.
Exclusion criteria
1. Presence of other active malignant tumors (excluding indolent tumors that have been cured, such as basal cell carcinoma of the skin and carcinoma in situ of the cervix); 2. Central nervous system leukemia; 3. Existence of uncontrolled severe infection (such as sepsis, fungal pneumonia, active tuberculosis, etc.); 4. History of severe heart disease, including but not limited to: severe arrhythmias (such as ventricular tachycardia, atrial fibrillation with rapid ventricular rate, etc.), history of myocardial infarction (within the past 6 months), severe heart failure (NYHA functional class ≥3), etc.; 5. Women who are pregnant or breastfeeding; women planning pregnancy or men of reproductive potential who have not used effective contraception during the study and within 6 months after treatment; 6. Known allergy to venetoclax, cytarabine, or other components of the combination regimen in the study; 7. Having mental illness (such as schizophrenia, major depressive disorder, etc.) or cognitive dysfunction that prevents cooperation with study follow-up and treatment; 8. Active hepatitis B virus infection (HBV DNA positive), active hepatitis C virus infection (HCV RNA positive), or human immunodeficiency virus (HIV) infection; 9. Undergoing major surgery, radiation therapy, other chemotherapy drugs, or investigational drug treatments within 3 weeks prior to study drug treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Measurable residual disease (MRD) negative | At the end of cycle 2 (28 days for a cycle) | MRD is monitored using flow cytometric analysis with a positive MRD threshold of 0.1%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Incidence of Recurrence (CIR) | 2 years | Assess the risk of leukemia recurrence after the consolidation |
| Overall survival (OS) | 2 years | OS is calculated from enrollment to death or the last follow-up. |
| Disease Free Survival (DFS) | 2 years | It refers to the time from the start of the consolidation to disease recurrence or death from any cause or the last follow-up. |
| Aderse events | At the end of cycle 2 (28 days for a cycle) | Side effects of the consolidations including haematological and non-haematological toxicity. |
| The rate of being bridged to allogeneic hematopoietic stem cell transplantation | 2 years | To assess how many patients are needed to accept allogeneic hematopoietic stem cell transplantation after the consolidation. |
Countries
China
Outcome results
None listed