Clinical trial NCT06763666: CLAG+VEN vs CLAG in the Treatment of Relapsed/Refractory AML
Official title: A Multicenter, Prospective, Randomized Controlled Study Comparing the Efficacy and Safety of CLAG(Cladribine, Cytarabine and G-CSF) Combined With Venetoclax and CLAG in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Relapsed/Refractory AML
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
Collaborators: name: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Guangzhou No.12 People's Hospital
name: Guangzhou Panyu Central Hospital
name: Guangzhou General Hospital of Guangzhou Military Command
name: Guangzhou First People's Hospital
name: Foresea Life Insurance Guangzhou General Hospital
name: Guangdong Second Provincial General Hospital
name: Jiangmen Central Hospital
name: Shantou Central Hospital
name: Maoming People's Hospital
name: First Affiliated Hospital of Guangxi Medical University
name: Hainan General Hospital
name: Dongguan People's Hospital
name: Tungwah Hospital of Sun Yat-Sen University
name: Shenzhen Hospital of Southern Medical University
name: Central People's Hospital of Zhanjiang
name: ZhuHai Hospital
name: Shenzhen Second People's Hospital
name: Zhongshan People's Hospital, Guangdong, China
name: LiuZhou People's Hospital
name: First People's Hospital of Foshan
name: Southern Medical University, China
name: Affiliated Hospital of Guangdong Medical University
name: Guilin Medical University, China
name: Yuebei People's Hospital
name: Huizhou Municipal Central Hospital
name: Second Affiliated Hospital of Guangzhou Medical University
name: Peking University Shenzhen Hospital
First posted: 2025-01-08
Enrollment: 172
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multicenter, prospective, randomized controlled clinical study comparing the efficacy and safety of CLAG+VEN and CLAG regimens in relapsed/refractory(r/r) AML.

Detailed description: The efficacy and prognosis of relapsed/refractory(r/r) AML are very poor, and there is no standard chemotherapy regimen were defined for r/r AML. Cladribine, a purine analogue, exerts cytotoxic, proapoptotic, and antiproliferative effects on AML cells. Previous studies have confirmed the efficacy of cladribine in the treatment of r/r AML, with a response rate of 30-45%.Our previous experience has shown that CLAG in combination of venetoclax are effective with tolerable toxicity profiling. However, there is a lack of multicenter, prospective, randomized controlled trials to further confirm the results. Therefore, a clinical study is planned to evaluate the efficacy and safety of CLAG+VEN compared to CLAG in r/r AML who were eligible for intensive therapy.

Eligibility criteria: Inclusion Criteria:

1. Diagnosed of AML according to the World Health Organization (WHO) classification.
2. All patients should aged 18 to 65 years.
3. Diagnosed of relapsed and refractory AML, according to The guidelines for diagnosis and treatment of relapse /refractory acute myelogenous leukemia in China（2023）
4. Diagnostic criteria for relapsed AML: Leukemia cells reappear in the peripheral blood or primitive cells in the bone marrow ≥ 5% (excluding other reasons such as bone marrow regeneration after consolidation chemotherapy) after CR, or leukemia cell infiltration appears outside the marrow.
5. Diagnostic criteria for refractory AML: The newly diagnosed patients who failed to respond to two courses of standard treatment; Patients who relapsed within 12 months after consolidation intensive therapy; Patients who relapsed after 12 months and failed to respond to conventional chemotherapy; Patients with two or more recurrences; Patients with persistent extramedullary leukemia.
6. The score of Eastern Cooperative Oncology Group (ECOG) is 0-2.
7. Renal function: creatinine clearance rate ≥ 30ml/min.
8. Liver function: ALT\<5 times normal value, bilirubin\<3 times normal value.
9. Predicted survival ≥ 3 months.
10. Able to accept oral Venetoclax.
11. Sign an informed consent form and be able to understand and follow the procedures required by this protocol.

Exclusion Criteria:

1. Diagnosed of acute promyelocytic leukemia (AML-M3)
2. Patients with central nervous system (CNS) invasion.
3. Cardiac function \< grade 2.
4. Known human immunodeficiency virus (HIV) infection.
5. Other clinically significant uncontrolled conditions, including but not limited to: a. uncontrolled or active systemic infections (viruses, bacteria, or fungi); b. Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) requiring treatment; c. Secondary tumors requiring active treatment.
6. Allergy to experimental drugs.
7. Pregnant and lactating women.
8. Patients who ineligible for the study according to the investigator's assessment.

Primary outcomes:
measure: Composite Complete remission (cCR, CR+CRi)
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
Secondary outcomes:
measure: Overall Response rate (ORR)
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: MRDneg CR rate
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Overall Survival(OS)
timeFrame: 1 year post treatment
measure: Relapse free survival(RFS)
timeFrame: 1 year post treatment
measure: Duration of completed response(DoR)
timeFrame: 1 year post treatment
measure: Relapse rate
timeFrame: 1 year post treatment
measure: Incidence of Adverse Events
timeFrame: Duration of treatment, up to 1 year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Department of Hematology,Nanfang Hospital, Southern Medical University
state: Guangdong
Study officials:
affiliation: Nanfang Hospital, Southern Medical University
name: Guopan Yu
role: PRINCIPAL_INVESTIGATOR
References: