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

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

Overview

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.

Detailed 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.

Interventions

• Drug Azacytidine;Cytarabine;Aclacinomycin;Chidamide;Venetoclax;Granulocyte colony-stimulating factor
  1. Azacytidine (75mg/m2/day, days 1 to 7). 2. Cytarabine (75-100mg/m2 q12h, days 1 to 5). 3. Aclacinomycin(20mg/day, days 1,3,5). 4. Chidamide(30mg/day , days 1,4,8,11). 5. Venetoclax (100mg on day 1,200mg on day 2,400mg on days 3-14). 6. Granulocyte colony stimulating factor (300 μg/day, day 0 until agranulocytosis recovery)
• Drug Best-Available Therapy(BAT) Regimen
  1. 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) 2. 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) 3. 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) 4. DCAG regimen:Decitabine(20mg/m2,days 1 to 5)+Aclacin

Primary outcome measures

• Overall Response Rate (ORR) after 1 course of treatment [Time frame: 1 months after the start of study treatment]

Secondary outcome measures (9)

• Complete Remission (CR) Rate after 1 course of treatment [Time frame: 2 months after study treatment]
• Complete Remission (CR) Rate after 2 courses of treatment [Time frame: After two courses of chemotherapy (each course is 28 days)]
• Overall Response Rate (ORR) after 2 course of treatment [Time frame: After two courses of chemotherapy (each course is 28 days)]
• Rate of Minimal Residual Disease (MRD)-Negative Response [Time frame: After two courses of chemotherapy (each course is 28 days)]
• Event-free survival [Time frame: 180 days after study treatment]
• Overall Survival (OS) [Time frame: 180 days after study treatment]
• Treatment-related adverse events [Time frame: From the first dose of study treatment to 30 days after the discontinuation of treatment]
• Early death [Time frame: Within 30 days of the start of the first course of treatment]
• Disease-free survival [Time frame: 180 days after study treatment]

Eligibility criteria

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.)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Chinese PLA General Hospital — Beijing

Identifiers

NCT: NCT06084819 · S2023-413-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗