Relapsed/Refractory AML
Conditions
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.
Interventions
DRUGCladribine
Given IV
DRUGCytarabine
Given IV
DRUGG-CSF
Given SC
DRUGVenetoclax
Given PO
Sponsors
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Guangzhou No.12 People's Hospital
Guangzhou Panyu Central Hospital
Guangzhou General Hospital of Guangzhou Military Command
Guangzhou First People's Hospital
Foresea Life Insurance Guangzhou General Hospital
Guangdong Second Provincial General Hospital
Jiangmen Central Hospital
Shantou Central Hospital
Maoming People's Hospital
First Affiliated Hospital of Guangxi Medical University
Hainan General Hospital
Dongguan People's Hospital
Tungwah Hospital of Sun Yat-Sen University
Shenzhen Hospital of Southern Medical University
Central People's Hospital of Zhanjiang
ZhuHai Hospital
Shenzhen Second People's Hospital
Zhongshan People's Hospital, Guangdong, China
LiuZhou People's Hospital
First People's Hospital of Foshan
Southern Medical University, China
Affiliated Hospital of Guangdong Medical University
Guilin Medical University, China
Yuebei People's Hospital
Huizhou Municipal Central Hospital
Second Affiliated Hospital of Guangzhou Medical University
Peking University Shenzhen Hospital
Nanfang Hospital, Southern Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite Complete remission (cCR, CR+CRi) | At the end of Cycle 1 (each cycle is 28 days) | Will compare composite complete remission(CR+CRi: complete response \[CR\] and complete response with incomplete blood count recovery \[CRi\]) between CLAGV regimen and CLAG regimen |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MRDneg CR rate | At the end of Cycle 1 (each cycle is 28 days) | Will compare MRD-negative cCR rates between the study arms |
| Overall Survival(OS) | 1 year post treatment | Will compare OS between the study arms |
| Relapse free survival(RFS) | 1 year post treatment | Will compare RFS between the study arms |
| Overall Response rate (ORR) | At the end of Cycle 1 (each cycle is 28 days) | Will compare ORR(completed remission\[CR\], completed remission with incomplete blood count recovery\[CRi\], and partial remission\[PR\]) rates between the study arms |
| Relapse rate | 1 year post treatment | Will compare relapse rate between the study arms |
| Incidence of Adverse Events | Duration of treatment, up to 1 year | Will use the CTCAE (National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events) version 5.0 for toxicity and adverse event reporting. Will describe the incidence of infection and treatment-related adverse events. |
| Duration of completed response(DoR) | 1 year post treatment | Will compare DoR between the study arms |
Countries
China
Contacts
Primary ContactGuopan Yu
Backup ContactGuopan Yu
Outcome results
None listed