Clinical trial NCT06084819: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Relapsed/Refractory Acute Myeloid Leukemia
Keywords: Relapsed/Refractory Acute Myeloid Leukemia
Lead sponsor: Chinese PLA General Hospital
Sponsor class: OTHER
Collaborators: name: 940 Hospital of the People's Liberation Army Joint Logistic Support Force
name: The General Hospital of Western Theater Command
name: The General Hospital of Northern Theater Command
name: The 960th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army
name: Air Force Military Medical University, China
name: Yantai Yuhuangding Hospital
name: People's Liberation Army (PLA) Strategic Support Force Characteristic Medical Center
name: First Hospital of China Medical University
First posted: 2023-10-16
Enrollment: 200
Sex: ALL
Minimum age (years): 14
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

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.)

Primary outcomes:
measure: Overall Response Rate (ORR) after 1 course of treatment
timeFrame: 1 months after the start of study treatment
Secondary outcomes:
measure: Complete Remission (CR) Rate after 1 course of treatment
timeFrame: 2 months after study treatment
measure: Complete Remission (CR) Rate after 2 courses of treatment
timeFrame: After two courses of chemotherapy (each course is 28 days)
measure: Overall Response Rate (ORR) after 2 course of treatment
timeFrame: After two courses of chemotherapy (each course is 28 days)
measure: Rate of Minimal Residual Disease (MRD)-Negative Response
timeFrame: After two courses of chemotherapy (each course is 28 days)
measure: Event-free survival
timeFrame: 180 days after study treatment
measure: Overall Survival (OS)
timeFrame: 180 days after study treatment
measure: Treatment-related adverse events
timeFrame: From the first dose of study treatment to 30 days after the discontinuation of treatment
measure: Early death
timeFrame: Within 30 days of the start of the first course of treatment
measure: Disease-free survival
timeFrame: 180 days after study treatment
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
Study officials:
affiliation: Chinese PLA General Hospital
name: Daihong Liu, doctor
role: STUDY_CHAIR
References: