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

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)

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).

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Venetoclax in combination with azacitidine and CAG

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 62 patients will take part in this trial.

• Study Type: Interventional
• Enrollment (Anticipated): 62
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Sanbin Wang, MD; Phone Number: +86 13187424131; Email: Wangsanbin2022@126.com
• Study Contact Backup: Name: Lin Liu, MD

Study Locations

• China
  • Yunnan
    • Kunming, Yunnan, China, 650000
      • Recruiting
      • 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
      • Contact: Lin Liu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment group; 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.

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.; Other Names: VA-CAG regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Hematology department of the 920th hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2022
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: December 10, 2022
• First Submitted That Met QC Criteria: December 20, 2022
• First Posted (Actual): December 23, 2022

Study Record Updates

• Last Update Posted (Actual): December 23, 2022
• Last Update Submitted That Met QC Criteria: December 20, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Cytarabine; Venetoclax; Azacitidine; Granulocyte colony-stimulating factor(G-CSF); Aclarubicin
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Venetoclax; Azacitidine
• Other Study ID Numbers: KMHD-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No