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

Chinese PLA General Hospital (301 Hospital)

Status and phase: Enrolling; Phase 2

Conditions: Relapsed/Refractory Acute Myeloid Leukemia

Treatments: Drug: Best-Available Therapy(BAT) Regimen; Drug: Azacytidine;Cytarabine;Aclacinomycin;Chidamide;Venetoclax;Granulocyte colony-stimulating factor

Study type: Interventional

Funder types: Other

Identifiers

NCT06084819

S2023-413-01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 200 estimated patients

Sex: All

Ages: 14 to 75 years old

Volunteers: No Healthy Volunteers

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.)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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200 participants in 2 patient groups

Venetoclax Combined With CACAG Regimen

Experimental group

Description:

Venetoclax combined with CACAG regimen for relapsed/refractory AML. Recipients were randomized and those entering the experimental group received azacytidine,cytarabine,aclacinomycin,chidamide,venetoclax and granulocyte colony-stimulating factor. Azacytidine was used as 75 mg/m2/day from day 1 to day 7.Cytarabine was used as 75-100 mg/m2 bid from day 1 to day 5. Aclacinomycin was used as 20 mg/day on days 1,3,5. Chidamide was used as 30 mg/day on days 1,4,8,11. Venetoclax was used as 400 mg/day from day 1 to day 14.Granulocyte colony-stimulating factor was used as 300 ug/day from day 0 until agranulocytosi recovery.

Treatment:

Drug: Azacytidine;Cytarabine;Aclacinomycin;Chidamide;Venetoclax;Granulocyte colony-stimulating factor

Best-Available Therapy(BAT) Regimen

Active Comparator group

Description:

BAT regimen for relapsed/refractory AML.Recipients were randomized and those entering this group received FLAG/CLAG/MAE/DCAG/HAA/HAD regimen.

Treatment:

Drug: Best-Available Therapy(BAT) Regimen