Acute Myeloid Leukemia
Conditions
Keywords
Acute Myeloid Leukemia, First Line Therapy
Brief summary
The purpose of this study is to compare the efficacy and safety of venetoclax combined with CACAG regimen with the traditional "3+7" regimen in the treatment of newly diagnosed acute myeloid leukemia.
Detailed description
Despite the availability of hematopoietic stem cell transplantation and the emergence of many new therapeutic drugs, the prognosis of newly diagnosed acute myeloid leukemia is still poor.Over the past years, combination chemotherapy with anthracycline and standard dose cytarabine (standard "3+7" induction therapy) remains the standard induction. In order to improve the outcome of patients with de novo AML, we developed a venetoclax combined with CACAG regimen in the treatment of de novo AML. In this study, we intent to compare the efficacy and safety of venetoclax combined with CACAG regimen with the traditional "3+7" regimen in the treatment of newly diagnosed acute myeloid leukemia.
Interventions
1. Azacytidine (75 mg/m2/day, days 1 to 7). 2. Cytarabine (75-100 mg/m2 bid, days 1 to 5). 3. Aclacinomycin(20 mg/day, days 1,3,5). 4. Chidamide (30 mg/day , days 1,4,8,11). 5. Venetoclax (400 mg/day, days 1 to 14,Combined with posaconazole reduced to 100 mg/day,Combined with voriconazole reduced to 200 mg/day ). 6. Granulocyte colony-stimulating factor (300 μg/day, day 0 until agranulocytosis recovery)
DRUG"3+7"
IA regimen: 1. Idarubicin (8-10 mg/m2) for 3 days . 2. Cytarabine (75-100mg/m2, every 12 hrs) for 7 days. DA regimen: 1. Daunorubicin(60 mg/m2) for 3 days. 2. Cytarabine (75-100mg/m2, every 12 hrs) for 7 days.
Sponsors
Chinese PLA General Hospital
940 Hospital of the People's Liberation Army Joint Logistic Support Force
The General Hospital of Western Theater Command
The General Hospital of Northern Theater Command
The 960th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army
Air Force Military Medical University, China
Yantai Yuhuangding Hospital
People's Liberation Army (PLA) Strategic Support Force Characteristic Medical Center
First Hospital of China Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Patients who are able to understand and willing to sign the informed consent form (ICF). * All patients should aged 14 to75 years,no gender limitation. * Patients who are newly diagnosed with AML(no M3). * Liver function: ALT and AST≤2.5 times the upper limit of normal ,bilirubin≤2 times the upper limit of normal; * Renal function: creatinine ≤the upper limit of normal; * Patients without any uncontrolled infections , without organ dysfunction or without severe mental illness; * The score of Eastern Cooperative Oncology Group (ECOG) is 0-2, and the predicted survival ≥ 4 months. * Patients without severe allergic constitution.
Exclusion criteria
* Patients with allergy or contraindication to the study drug; * Female patients who are pregnant or breast-feeding. * Patients with a known history of alcohol or drug addiction on the basis that there could be a higher risk of non-compliance to study treatment; * Patients with mental illness or other states unable to comply with the protocol; * Less than 6 weeks after surgical operation of important organs. * Liver function: ALT and AST\>2.5 times the upper limit of normal ,bilirubin\> 2 times the upper limit of normal;Renal function: creatinine \>the upper limit of normal; * The patient is not suitable for this clinical trial (poor compliance, substance abuse, etc.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) after 1 course of treatment | 1 months after the start of study treatment | Defined as the percentage of participants achieving a best overall response of complete response (CR) or CR with incomplete blood count recovery (CRi).Biological characteristics exploratory studies were analyzed by single-cell sequencing and Atac-seq. Further, according to European LeukemiaNet risk group, we analyzed the outcomes of patients by molecular subtype as a sub-group analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 180 days after study treatment | Defined as the time from joining the clinical study to death due to any cause. |
| Complete Remission (CR) Rate after 1 course of treatment | 2 months after study treatment | Defined in accordance with the IWG Response Criteria in AML. Bone marrow blasts\<5 percent; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count \>1.0 x 109/L (1000/µL); platelet count \>100 x 109/L (100,000/µL); independence of red cell transfusions. |
| Complete Remission (CR) Rate after 2 courses of treatment | after two courses of chemotherapy (each course is 28 days) | Defined in accordance with the IWG Response Criteria in AML. Bone marrow blasts\<5 percent; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count \>1.0 x 109/L (1000/µL); platelet count \>100 x 109/L (100,000/µL); independence of red cell transfusions. |
| Overall Response Rate (ORR) after 2 course of treatment | after two courses of chemotherapy (each course is 28 days) | Defined as the percentage of participants achieving a best overall response of complete response (CR) or CR with incomplete blood count recovery (CRi).Biological characteristics exploratory studies were analyzed by single-cell sequencing and Atac-seq. Further, according to European LeukemiaNet risk group, we analyzed the outcomes of patients by molecular subtype as a sub-group analysis. |
| Rate of Minimal Residual Disease (MRD)-Negative Response | after two courses of chemotherapy (each course is 28 days) | Percentage of participants who achieved MRD-negative response, defined as \< 1 leukemia cell per 10,000 leukocytes as assessed by flow cytometry. |
| Treatment-related adverse events | From the first dose of study treatment to 30 days after the discontinuation of treatment | Defined as adverse events that occurred from the first dose of study treatment to 30 days after the discontinuation of treatment. |
| Early death | Within 30 days of the start of the first course of treatment | Defined as death within 30 days of chemotherapy. |
| Event-free survival | 180 days after study treatment | Defined as the time interval from treatment initiation to the occurrence of induction failure,relapse,or death,whichever came first. |
| Disease-free survival | 180 days after study treatment | Defined as the time interval from disease remission to the occurrence of relapse or death,whichever came first. |
Countries
China
Contacts
STUDY_CHAIRDaihong Liu, doctor
Chinese PLA General Hospital
Outcome results
None listed