A Clinical Study of VA-CAG as Induction Therapy in Newly Diagnosed AML Patients

Acute Myeloid Leukemia Clinical Trial

Official title:

A Phase II Study to Evaluate the Safety and Efficacy of Venetoclax in Combination With Azacitidine and CAG(VA-CAG) as Induction Therapy in Newly Diagnosed Patients With Acute Myeloid Leukemia(AML)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05662956
• Other study ID #: KMHD-01
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 1, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: December 2022
• Source: Hematology department of the 920th hospital
• Contact: Sanbin Wang, MD
• Phone: 13187424131
• Email: Wangsanbin2022[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to assess the therapeutic efficacy and safety of venetoclax in combination with azacitidine and CAG(VA-CAG) as induction regimen in newly diagnosed young patients with acute myeloid leukemia(AML).

Description:

This is an open-label, multicenter, phase II clinical trial to assess the therapeutic efficacy and safety of venetoclax in combination with azacitidine (VA) and CAG (G-CSF priming, low dose cytarabine, and aclarubicin) as induction regimen in newly diagnosed patients with acute myeloid leukemia (AML). The combination of venetoclax and azacitidine is the standard therapy for elderly (> 60 year old) patients with newly diagnosed AML who are not eligible for intensive chemotherapy. Previous studies have shown that venetoclax plus intense chemotherapy represent promising efficacy in de novo AML patients with high complete remission rates and good tolerance. The preliminary results suggest that venetoclax in combination with azacitidine and CAG are well tolerated and effective for newly diagnosed young patients with AML. Thus, this phase II clinical trial is going to further explore its efficacy and safety. It is expected that about 62 patients will take part in this trial.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 62
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Patients = 18 years old and = 65 years old

2. Newly diagnosed as AML patients according to 2016 World Health Organization (WHO) classification;

3. Patients without receiving prior therapy for AML;

4. Eastern Cooperative Oncology Group (ECOG) Performance status score less than 3;

5. Liver function: Total bilirubin ?2 upper limit of normal (ULN); aspartate aminotransferase (AST) ?3 ULN; alanine aminotransferase (ALT)?3 ULN

6. Renal function:Ccr(Creatinine Clearance Rate) ?30 ml/min; Scr (serum creatinine) ?2 ULN

7. Heart function: left ventricular ejection fraction ?45%

8. Patients must participate in this clinical trial voluntarily and sign an informed consent form.

Exclusion Criteria:

1. Acute promyeloid leukemia;

2. AML with central nervous system (CNS) infiltration;

3. Patients have received prior hypomethylating agents (HMA) therapy for myelodysplastic syndrome (MDS) and progressed to AML;

4. Patients with a life expectancy <3 months

5. Patients with uncontrolled active infection;

6. HIV infection;

7. Evidence of other clinically significant uncontrolled condition(s) including, but not limited to: a) Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment; b) An active second cancer that requires treatment within 6 months of study entry.

8. Female who are pregnant, breast feeding or childbearing potential.

9. Patients deemed unsuitable for enrollment by the investigator.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Venetoclax in combination with azacitidine and CAG
Induction: VA regimen: Drug: Venetoclax orally once daily (100 mg d1, 200 mg d2, 400 mg d3-21); Drug: Azacitidine 75 mg/m2 subcutaneously once daily on days 1-7. CAG regimen: Drug: Cytarabine 10mg/m2 subcutaneously q12h on days 1-7; Drug: Aclacinomycin 12-14mg/m2 on days 1,3,5,7; Drug: Granulocyte colony-stimulating factor 5ug/kg on days 0-8, discontinue if WBC >20×10^9/L; Consolidation: Drug: Cytarabine 3g/m2 q12h on days 1-3.

Locations

Country	Name	City	State
China	920th Hospital of Joint Logistics Support Force of People's Liberation Army of China	Kunming	Yunnan

Sponsors (1)

Lead Sponsor	Collaborator
Hematology department of the 920th hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate (ORR)	The overall remission rate (ORR) was defined as the percentage of patients who achieved complete remission (CR), complete remission with incomplete count recovery (CRi), or morphologic leukemia free state (MLFS) per the International Working Group criteria for AML.	At the end of Cycle 1 and Cycle 2 of induction(each cycle is 28 days)
Secondary	Incidence of Treatment-Emergent Adverse Events (>=grade 3 )	Safety and tolerability analysis will be assessed by the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0.	Up to 2 years
Secondary	Duration of myelosuppression	The duration of absolute value of peripheral blood neutrophils <0.5×10^9/L and platelet count <50×10^9/L during myelosuppression.	Up to 2 years
Secondary	Leukaemia-free survival	Leukaemia-free survival will be defined as the time since date of CR until either relapse or death in remission.	Up to 2 years
Secondary	Overall survival	Overall Survival will be defined as the time from administration of the initial doses until death from any cause.	Up to 2 years
Secondary	Rate of Minimal Residual Disease (MRD) negativity	Percentage of participants who converted to MRD < 10^-3 by flow cytometry before initiation of consolidation therapy.	Up to 2 years