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

Phase 1

Recruiting

• Conditions: Acute Myeloid Leukemia
• Interventions: Drug: Venetoclax in combination with azacitidine and CAG

• Registration Number: NCT05662956
• Lead Sponsor: Hematology department of the 920th hospital

Brief 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).

Detailed 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 100 patients will take part in this trial.

Study Timeline

• Study Start: 2022-12-01
• Study First Submitted: 2022-12-10
• Study First Submitted QC: 2022-12-20
• Study First Posted: 2022-12-23
• Status Verified: 2024-01
• Last Update Submitted: 2024-08-11
• Last Update Posted: 2024-08-13
• Primary Completion: 2024-08-15
• Study Completion: 2024-09-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 104

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment group	Venetoclax in combination with azacitidine and CAG	Induction: Subjects who meet the enrollment conditions will receive Venetoclax plus Azacitidine and CAG(VA-CAG) . Participants will receive this induction Therapy as azacitidine on days 1-7, venetoclax aily on days 1-28, cytarabine q12h on days 1-7, aclacinomycin on days 1,3,5,7, and granulocyte colony-stimulating factor on days 0-8. Participants will receive second induction if not reach complete remission. Consolidation: If patients are intermediate or poor risk and have plans for allogeneic hematopoietic stem-cell transplantation(allo-HSCT) , high dose cytarabine (3g/m2 q12h days 1-3) for 1-2 cycles and follow up with allo-HSCT. In other cases, high dose cytarabine for 4 cycles.

Primary Outcome Measures

Name	Time	Method
Overall response rate (ORR)	At the end of Cycle 1 and Cycle 2 of induction(each cycle is 28 days)	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.

Secondary Outcome Measures

Name	Time	Method
Leukaemia-free survival	Up to 2 years	Leukaemia-free survival will be defined as the time since date of CR until either relapse or death in remission.
Incidence of Treatment-Emergent Adverse Events (>=grade 3 )	Up to 2 years	Safety and tolerability analysis will be assessed by the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0.
Duration of myelosuppression	Up to 2 years	The duration of absolute value of peripheral blood neutrophils \<0.5×10\^9/L and platelet count \<50×10\^9/L during myelosuppression.
Rate of Minimal Residual Disease (MRD) negativity	Up to 2 years	Percentage of participants who converted to MRD \< 10\^-3 by flow cytometry before initiation of consolidation therapy.
Overall survival	Up to 2 years	Overall Survival will be defined as the time from administration of the initial doses until death from any cause.

Trial Locations

Locations (1)

920th Hospital of Joint Logistics Support Force of People's Liberation Army of China; 🇨🇳 Kunming, Yunnan, China