Acute Myeloid Leukemia, First Line Therapy
Conditions
Brief summary
The purpose of this study is to compare the efficacy and safety of venetoclax combined with the CACAG regimen with the traditional "3+7" regimen in the treatment of newly diagnosed intermediate- or high-risk acute myeloid leukemia (AML).
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 intermediate- or high-risk acute myeloid leukemia.
Interventions
Azacytidine (75 mg/m2/day, days 1 to 7). Cytarabine (75-100 mg/m2 bid, days 1 to 5). Aclacinomycin(20 mg/day, days 1,3,5). Chidamide (30 mg/day , days 1,4,8,11). Venetoclax (400 mg/day, days 1 to 14,Combined with posaconazole reduced to 100 mg/day,Combined with voriconazole reduced to 200 mg/day ). Granulocyte colony-stimulating factor (300 μg/day, day 0 until agranulocytosis recovery)
DRUG"3+7"
IA regimen: Idarubicin (8-10 mg/m2) for 3 days . Cytarabine (75-100mg/m2, every 12 hrs) for 7 days. DA regimen: Daunorubicin(60 mg/m2) for 3 days. Cytarabine (75-100mg/m2, every 12 hrs) for 7 days.
Sponsors
Chinese PLA General Hospital
First Affiliated Hospital of Harbin Medical University
Yantai Yuhuangding Hospital
The General Hospital of Western Theater Command
940 Hospital of the People's Liberation Army Joint Logistic Support Force
960th Hospital of Joint Logistics Support Force of People's Liberation Army of China
Jining First People's Hospital
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
Age 14 to 75 years (no gender limitation) Newly diagnosed with intermediate- or high-risk AML (excluding M3) Liver function: ALT and AST ≤ 2.5 times upper limit of normal; bilirubin ≤ 2 times upper limit of normal Renal function: creatinine ≤ upper limit of normal No uncontrolled infections, organ dysfunction, or severe mental illness ECOG performance status score of 0-2 and predicted survival ≥ 4 months No severe allergic constitution
Exclusion criteria
Allergy or contraindication to the study drug Pregnant or breastfeeding female patients Known history of alcohol or drug addiction (due to potential non-compliance) Mental illness or conditions preventing protocol compliance Less than 6 weeks after major organ surgery Liver function: ALT and AST \> 2.5 times upper limit of normal; bilirubin \> 2 times upper limit of normal Renal function: creatinine \> upper limit of normal Deemed unsuitable for the clinical trial (poor compliance, substance abuse, etc.) \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite Complete Remission (CRc) Rate after 1 course of treatment | 1 months after study treatment | a combination of complete remission (CR) and complete remission with incomplete blood count recovery (CRi) |
Secondary
| 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), CR with incomplete blood count recovery (CRi), or partial response (PR).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. |
| Complete Remission (CR) Rate after 1 courses of treatment | after 1 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. |
| Rate of Minimal Residual Disease (MRD)-Negative Response | after each 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. |
| 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. |
| Overall Survival | 180 days after study treatment | Defined as the time from joining the clinical study to death due to any cause. |
| 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. |
| 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. |
| Early death | Within 30 days of the start of the first course of treatment | Defined as death within 30 days of chemotherapy. |
| Complete Remission with Incomplete Blood Count Recovery (CRi)after 1 courses of treatment | after 1 courses of chemotherapy (each course is 28 days) | Disappearance of leukemia blasts in the bone marrow (\<5% blasts) but without full recovery of blood counts (neutrophils \<1.0 x 10⁹/L and/or platelets \<100 x 10⁹/L). |
Countries
China
Outcome results
None listed