Clinical Study of Venetoclax Combined With CACAG Regimen in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia

Relapsed/Refractory Acute Myeloid Leukemia Clinical Trial

Official title:

A Prospective,Randomized,and Comparative Study on the Efficacy of Venetoclax Combined With CACAG Regimen and BAT Regimen in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06084819
• Other study ID #: S2023-413-01
• Status: Recruiting
• Phase: Phase 2
• 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
• 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.)

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Relapsed/Refractory Acute Myeloid Leukemia

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