CLAG+VEN vs CLAG in the Treatment of Relapsed/Refractory AML

Nanfang Hospital, Southern Medical University

Status and phase: Not yet enrolling; Phase 4

Conditions: Relapsed/Refractory AML

Treatments: Drug: Venetoclax; Drug: G-CSF; Drug: Cytarabine; Drug: Cladribine

Study type: Interventional

Funder types: Other

Identifiers

NCT06763666

NFEC-2024-639

Details and patient eligibility

About

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.

Full 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.

Enrollment: 172 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

172 participants in 2 patient groups

CLAGV regimen

Experimental group

Description:

CLAG combined with venetoclax for relapsed/refractory AML. Patients were randomized and those entering the experimental group received cladribine, cytarabine, G-CSF and venetoclax. Venetoclax is administered orally at 400mg/d on days 2-8. When combination with P450 3A4 inhibitor, VEN should be reduced to 100-200mg/d and monitoring of VEN blood concentrations is recommended at qualified centers. Cladribine is administered intravenously at a dose of 5 mg/m2/d on days 1-5. Cytarabine is administered intravenously at a dose of 1g/m2/d on days 1-5, starting 2h after cladribine and maintained for more than 3h. The dose of G-CSF was 5ug/kg/d subcutaneously injected on days 0-5. Generally, starting 12 hours before the start of chemotherapy, if the absolute value of white blood cell count is ≥ 20×10\^9/L, the use is suspended.For patients with FLT3 mutations, corresponding inhibitors such as sorafenib and gilteritinib can be combined.

Treatment:

Drug: Cytarabine

Drug: Cladribine

Drug: G-CSF

Drug: Venetoclax

CLAG regimen

Active Comparator group

Description:

CLAG regimen for relapsed/refractory AML. Patients were randomized and those entering the experimental group received cladribine, cytarabine, G-CSF. Cladribine is administered intravenously at a dose of 5 mg/m2/d on days 1-5. Cytarabine is administered intravenously at a dose of 1g/m2/d on days 1-5, starting 2h after cladribine and maintained for more than 3h. The dose of G-CSF was 5ug/kg/d subcutaneously injected on days 0-5. Generally, starting 12 hours before the start of chemotherapy, if the absolute value of white blood cell count is ≥ 20×10\^9/L, the use is suspended.For patients with FLT3 mutations, corresponding inhibitors such as sorafenib and gilteritinib can be combined.

Treatment:

Drug: Cytarabine

Drug: Cladribine

Drug: G-CSF