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).
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
160
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)
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.
Chinese PLA General Hospital
Beijing, Beijing Municipality, China
RECRUITINGComposite Complete Remission (CRc) Rate after 1 course of treatment
a combination of complete remission (CR) and complete remission with incomplete blood count recovery (CRi)
Time frame: 1 months after study treatment
Overall Response Rate (ORR) after 1 course of 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.
Time frame: 1 months after the start of study treatment
Complete Remission (CR) Rate after 1 courses of 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.
Time frame: after 1 courses of chemotherapy (each course is 28 days)
Rate of Minimal Residual Disease (MRD)-Negative Response
Percentage of participants who achieved MRD-negative response, defined as \< 1 leukemia cell per 10,000 leukocytes as assessed by flow cytometry.
Time frame: after each courses of chemotherapy (each course is 28 days)
Event-free survival
Defined as the time interval from treatment initiation to the occurrence of induction failure,relapse,or death,whichever came first.
Time frame: 180 days after study treatment
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Overall Survival
Defined as the time from joining the clinical study to death due to any cause.
Time frame: 180 days after study treatment
Treatment-related adverse events
Defined as adverse events that occurred from the first dose of study treatment to 30 days after the discontinuation of treatment.
Time frame: From the first dose of study treatment to 30 days after the discontinuation of treatment
Disease-free survival
Defined as the time interval from disease remission to the occurrence of relapse or death,whichever came first.
Time frame: 180 days after study treatment
Early death
Defined as death within 30 days of chemotherapy.
Time frame: Within 30 days of the start of the first course of treatment
Complete Remission with Incomplete Blood Count Recovery (CRi)after 1 courses of treatment
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).
Time frame: after 1 courses of chemotherapy (each course is 28 days)