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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT06084819
Other study ID # S2023-413-01
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date August 1, 2023
Est. completion date January 31, 2026

Study information

Verified date February 2023
Source Chinese PLA General Hospital
Contact Daihong Liu, doctor
Phone +8613681171597
Email daihongrm@163.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this study is to compare the efficacy and safety of venetoclax combined with CACAG regimen with BAT regimen in the treatment of relapsed/refractory acute myeloid leukemia.


Description:

Despite advances in therapies for acute myeloid leukemia (AML) in the past decades, some patients still suffer from relapsed/refractory (R/R) disease, resulting in poor outcomes. With a median overall survival (OS) of 4-7 months under classic chemotherapy approaches, it is imperative to explore new treatment options.Accumulating research has demonstrated the importance of epigenetic modification in the pathogenesis of chemoresistance. Recent studies have shown that combining venetoclax with hypomethylating agents (HMAs) such as azacitidine, or low-dose cytarabine (LDAC) improves the response and survival rates in R/R AML patients. To enhance the response rate, we designed a regimen that combines chidamide, azacitidine, cytarabine, aclarubicin, and G-CSF with venetoclax (CACAG+VEN regimen) for the treatment of patients with R/R AML. In this study, we intend to compare the efficacy and safety of venetoclax combined with the CACAG regimen with Best-Available Therapy(BAT) regimen in the treatment of relapsed/refractory acute myeloid leukemia.


Recruitment information / eligibility

Status Recruiting
Enrollment 200
Est. completion date January 31, 2026
Est. primary completion date January 31, 2026
Accepts healthy volunteers No
Gender All
Age group 14 Years to 75 Years
Eligibility Inclusion Criteria: - Patients who are able to understand and willing to sign the informed consent form (ICF). - All patients should aged 14 to 75 years,no gender limitation. - Patients with R/R AML, diagnosed in accordance with the 2021 edition of the CMA criteria - 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 0-3,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.)

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Azacytidine;Cytarabine;Aclacinomycin;Chidamide;Venetoclax;Granulocyte colony-stimulating factor
Azacytidine (75mg/m2/day, days 1 to 7). Cytarabine (75-100mg/m2 q12h, days 1 to 5). Aclacinomycin(20mg/day, days 1,3,5). Chidamide(30mg/day , days 1,4,8,11). Venetoclax (100mg on day 1,200mg on day 2,400mg on days 3-14). Granulocyte colony stimulating factor (300 µg/day, day 0 until agranulocytosis recovery)
Best-Available Therapy(BAT) Regimen
FLAG regimen:Fludarabine(30mg/m2,days 1-5)+Cytarabine (1-2g/m2 applied 4h after fludarabine, days 1 to 5)+Granulocyte colony-stimulating factor(300ug/day,days 0 to 5) CLAG regimen:Cladribine(5mg/2,days 1-5)+Cytarabine (1-2g/m2 applied 4h after fludarabine, days 1 to 5)+Granulocyte colony-stimulating factor(300ug/day,days 0 to 5) MAE regimen:Mitox(10mg/m2,days 1 to 5)+VP-16(100mg/m2,days 1 to 5)+Cytarabine (100-150mg/m2,days 1 to 7) DCAG regimen:Decitabine(20mg/m2,days 1 to 5)+Aclacinomycin(20mg/day on days 1,3,5)+Cytarabine (100mg q12h,days 1 to 5)+Granulocyte colony-stimulating factor(300 ug/day,day 0 until agranulocytosi recovery) HAA regimen:HHT(2mg/m2,days 1 to 7)+Aclacinomycin(20mg/day,days 1 to 7) and Cytarabine (100-200 mg/m2, days 1 to 5); HAD regimen:HHT(2mg/m2,days 1 to 7)+Daunorubicin(45mg/m2/day,days 1 to 3)+Cytarabine (100-200 mg/m2,days 1 to 5).

Locations

Country Name City State
China Chinese PLA General Hospital Beijing Beijing

Sponsors (9)

Lead Sponsor Collaborator
Chinese PLA General Hospital Air Force Military Medical University, China, First Hospital of China Medical University, People's Liberation Army (PLA) Strategic Support Force Characteristic Medical Center, The 940th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, The 960th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, The General Hospital of Northern Theater Command, The General Hospital of Western Theater Command, Yantai Yuhuangding Hospital

Country where clinical trial is conducted

China, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. 1 months after the start of study treatment
Secondary Complete Remission (CR) Rate after 1 course 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. 2 months after study treatment
Secondary Complete Remission (CR) Rate after 2 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. After two courses of chemotherapy (each course is 28 days)
Secondary Overall Response Rate (ORR) after 2 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. After two courses of chemotherapy (each course is 28 days)
Secondary 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. After two courses of chemotherapy (each course is 28 days)
Secondary Event-free survival Defined as the time interval from treatment initiation to the occurrence of induction failure,relapse,or death,whichever came first. 180 days after study treatment
Secondary Overall Survival (OS) Defined as the time from joining the clinical study to death due to any cause. 180 days after study treatment
Secondary 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. From the first dose of study treatment to 30 days after the discontinuation of treatment
Secondary Early death Defined as death within 30 days of chemotherapy. Within 30 days of the start of the first course of treatment
Secondary Disease-free survival Defined as the time interval from disease remission to the occurrence of relapse or death,whichever came first. 180 days after study treatment
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