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

NCT06763666 | Not Yet Recruiting Phase 4

• 1 other identifier: NFEC-2024-639
• Study Type: interventional
• Target: 172
• Locations: 1 country
• Sites: 1

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.

Conditions

Relapsed/Refractory AML

Outcome Measures

Primary Outcomes (1)

• Composite Complete remission (cCR, CR+CRi)

  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

  At the end of Cycle 1 (each cycle is 28 days)

Secondary Outcomes (7)

• Overall Response rate (ORR)

  At the end of Cycle 1 (each cycle is 28 days)

• MRDneg CR rate

  At the end of Cycle 1 (each cycle is 28 days)

• Overall Survival(OS)

  1 year post treatment

• Relapse free survival(RFS)

  1 year post treatment

• Duration of completed response(DoR)

  1 year post treatment

Study Arms (2)

CLAGV regimen

EXPERIMENTAL

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.

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

CLAG regimen

ACTIVE COMPARATOR

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.

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

Interventions

Cladribine DRUG

Given IV

Also known as: 2-CdA, CdA

CLAG regimen; CLAGV regimen

Cytarabine DRUG

Given IV

Also known as: Ara-C

CLAG regimen; CLAGV regimen

G-CSF DRUG

Given SC

Also known as: Filgrastim, Granulocyte Colony-stimulating Factor

CLAG regimen; CLAGV regimen

Venetoclax DRUG

Given PO

Also known as: Venclexta

CLAGV regimen

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed of AML according to the World Health Organization (WHO) classification.
• All patients should aged 18 to 65 years.
• Diagnosed of relapsed and refractory AML, according to The guidelines for diagnosis and treatment of relapse /refractory acute myelogenous leukemia in China（2023）
• 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.
• 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.
• The score of Eastern Cooperative Oncology Group (ECOG) is 0-2.
• Renal function: creatinine clearance rate ≥ 30ml/min.
• Liver function: ALT\<5 times normal value, bilirubin\<3 times normal value.
• Predicted survival ≥ 3 months.
• Able to accept oral Venetoclax.
• Sign an informed consent form and be able to understand and follow the procedures required by this protocol.

You may not qualify if:

• Diagnosed of acute promyelocytic leukemia (AML-M3)
• Patients with central nervous system (CNS) invasion.
• Cardiac function \< grade 2.
• Known human immunodeficiency virus (HIV) infection.
• 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.
• Allergy to experimental drugs.
• Pregnant and lactating women.
• Patients who ineligible for the study according to the investigator's assessment.

Sponsors & Collaborators

• Guangzhou No.12 People's Hospital: collaborator
• Guangzhou Panyu Central Hospital: collaborator
• Guangzhou General Hospital of Guangzhou Military Command: collaborator
• Guangzhou First People's Hospital: collaborator
• Foresea Life Insurance Guangzhou General Hospital: collaborator
• Guangdong Second Provincial General Hospital: collaborator
• Jiangmen Central Hospital: collaborator
• Shantou Central Hospital: collaborator
• Maoming People's Hospital: collaborator
• First Affiliated Hospital of Guangxi Medical University: collaborator
• Hainan General Hospital: collaborator
• Dongguan People's Hospital: collaborator
• Tungwah Hospital of Sun Yat-Sen University: collaborator
• Shenzhen Hospital of Southern Medical University: collaborator
• Central People's Hospital of Zhanjiang: collaborator
• ZhuHai Hospital: collaborator
• Shenzhen Second People's Hospital: collaborator
• Zhongshan People's Hospital, Guangdong, China: collaborator
• LiuZhou People's Hospital: collaborator
• First People's Hospital of Foshan: collaborator
• Southern Medical University, China: collaborator
• Affiliated Hospital of Guangdong Medical University: collaborator
• Guilin Medical University, China: collaborator
• Yuebei People's Hospital: collaborator
• Huizhou Municipal Central Hospital: collaborator
• Second Affiliated Hospital of Guangzhou Medical University: collaborator
• Peking University Shenzhen Hospital: collaborator
• Nanfang Hospital, Southern Medical University: lead
• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: collaborator

Study Sites (1)

Department of Hematology,Nanfang Hospital, Southern Medical University

Guangzhou, Guangdong, 510515, China

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Cladribine; Cytarabine; Granulocyte Colony-Stimulating Factor; Filgrastim; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Guopan Yu

  Nanfang Hospital, Southern Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Guopan Yu

CONTACT

+8615876559968; yugpp@163.com

Guopan Yu

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 30, 2024
• First Posted: January 8, 2025
• Study Start: February 1, 2025
• Primary Completion: June 1, 2025
• Study Completion: December 1, 2025
• Last Updated: January 8, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)