Venetoclax Combined With Azacitidine and CAG in Refractory/Relapse Acute Myeloid Leukemia

Phase II Trial of Venetoclax in Combination With Azacitidine and CAG as Induction Therapy in Patients With Refractory/Relapse Acute Myeloid Leukemia

This study aims to assess the therapeutic efficacy and safety of venetoclax in combination with azacitidine and CAG as induction regimen in Patients with Refreactory/Relapse Acute Myeloid Leukemia.

Study Overview

• Status: Recruiting
• Conditions: Refractory/Relapse Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Venetoclax

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 Patients with Refreactory/Relapse Acute Myeloid Leukemia(AML).

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. Our preliminary results suggest that venetoclax in combination with azacitidine and CAG are well tolerated and effective for patients who were diagnosed with refreactory/relapse AML. Thus, this phase II clinical trial is going to further explore its efficacy and safety. It is expected that about 42 patients will take part in this trial.

• Study Type: Interventional
• Enrollment (Anticipated): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Yunnan
    • Kunming, Yunnan, China
      • Recruiting
      • Department of Hematology,920th Hospital of Joint Logistic Support Force of People's Liberation
      • Contact: Lin Liu, Professor; Phone Number: 0871-64774206; Email: Wangsanbin2022@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients ≥ 18 years old and ≤ 65 years old
2. Refractory/Relapse AML patients according to 2016 World Health Organization (WHO) classification;
3. Eastern Cooperative Oncology Group (ECOG) Performance status score less than 3;
4. Liver function: Total bilirubin ≦2 upper limit of normal (ULN); aspartate aminotransferase (AST) ≦3 ULN; alanine aminotransferase (ALT)≦3 ULN
5. Renal function：Ccr（Creatinine Clearance Rate） ≧30 ml/min; Scr (serum creatinine) ≦2 ULN
6. Heart function: left ventricular ejection fraction ≧45%
7. Patients must participate in this clinical trial voluntarily and sign an informed consent form.

Exclusion Criteria:

1. Other diseases；
2. AML with central nervous system (CNS) infiltration；
3. Patients have received prior CAG or VA regimen before；
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: VACAG（Venetoclax Combined with Azacitidine and CAG）regimen; Participants will receive induction 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.

Drug: Venetoclax; 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 >20×109/L; Other Names: Cytarabine; Azacitidine; Granulocyte colony-stimulating factor; Aclacinomycin

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.	up to 2 cycles from the start of VACAG regimen (each cycle is 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Incidence of Treatment-Emergent Adverse Events	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 be defined as the time from administration of the initial doses until death from any cause.	up to 2 years

Collaborators and Investigators

• Sponsor: Hematology department of the 920th hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2023
• Primary Completion (Anticipated): February 1, 2024
• Study Completion (Anticipated): February 1, 2026

Study Registration Dates

• First Submitted: February 27, 2023
• First Submitted That Met QC Criteria: March 28, 2023
• First Posted (Actual): April 11, 2023

Study Record Updates

• Last Update Posted (Actual): April 11, 2023
• Last Update Submitted That Met QC Criteria: March 28, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Recurrence; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Adjuvants, Immunologic; Antibiotics, Antineoplastic; Venetoclax; Lenograstim; Azacitidine; Cytarabine; Aclacinomycins
• Other Study ID Numbers: KM02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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