Venetoclax Combining Chidamide and Azacitidine (VCA) in the Treatment of R/R AML

A Multi-center, Prospective, Single-arm Study of Venetoclax Combining Chidamide and Azacitidine (VCA) in the Treatment of Refractory/Relapsed Acute Myelogenous Leukemia (R/R AML)

The purpose of this study is to evaluate the safety and efficacy of Venetoclax Combining Chidamide and Azacitidine (VCA) in the Treatment of relapsed and/or refractory AML

Study Overview

• Status: Recruiting
• Conditions: Leukemia, Myeloid, Acute; Refractory Leukemia; Relapsed Adult AML
• Intervention / Treatment: Drug: venetoclax combining chidamide and azacitidine (VCA)

Detailed Description

Patients with relapsed and/or refractory AML have inferior outcomes. The regimen of Venetoclax and Azacitidine has been widely used in the treatment of RR AML and has proved to achieve CR rate of 30% ~ 40%. However, the median duration of response (DOR) of this regimen is about one year. Chidamide is a histone deacetylase (HDAC) inhibitor and preclinical data showed adding low-dose Chidamide to venetoclax could significantly promoted apoptosis of leukemia cell lines. Meanwhile, the Venetoclax Combining Chidamide and Azacitidine (VCA) regimen was applied to 2 patients with refractory AML. This regimen was well tolerated and both patients achieved CR after one cycle. Thus, we register this clinical trial and evaluate the safety and efficacy of VCA regimen.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Bing Xu, M.D.; Phone Number: +865922137255; Email: xubingzhangjian@126.com

Study Locations

• China
  • Fujian
    • Xiamen, Fujian, China, 361003
      • Recruiting
      • Bing Xu
      • Contact: Bing Xu
      • Principal Investigator: Bing Xu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18
• Relapsed and refractory patients with acute myeloid leukemia via morphology and immunology
• ECOG：0-2
• Life expectancy ≥ 3 months

• Adequate laboratory parameters during the screening period as evidenced by the following:

  1. Creatinine clearance≥30 mL/min and serum Creatinine ≤ 160µmol/L
  2. ALT and AST ≤ 3 × upper limit of normal (ULN)
  3. Able to understand and sign an informed consent form (ICF).

Exclusion Criteria:

• Diagnosis of acute promyelocytic leukemia (APL)
• Central nervous system leukemia

• Uncontrolled or significant cardiovascular disease, including any of the following:

  1. Bradycardia of less than 50 beats per minute, unless the subject has a pacemaker; Diagnosis of or suspicion of long QT syndrome (including family history of long QT syndrome);
  2. Systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg; History of clinically relevant ventricular arrhythmias (eg, ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes);
  3. History of second (Mobitz II) or third degree heart block (subjects with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker);
  4. History of uncontrolled angina pectoris or myocardial infarction within 6 months prior to Screening;
  5. History of New York Heart Association Class 3 or 4 heart failure;
  6. Complete left bundle branch block;
  7. Known history of left ventricular ejection fraction (LVEF) ≤45% or less than the institutional lower limit of normal;
• Active acute or chronic systemic fungal, bacterial, or viral infection not well controlled by antifungal, antibacterial or antiviral therapy;
• Suffered from other non-myeloid malignancies within 2 years, except adequately treated non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated with no evidence of disease
• Females who are pregnant or breastfeeding;
• Mental disorders that hinder research participation
• Previous solid organ transplantation (SCT treatment is allowed in advance, but if the patient has GVHD or is still receiving immunosuppression/GVHD treatment, it is not allowed)
• Any other situation where the investigator believes that the patient should not participate in this trial

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: venetoclax combining chidamide and azacitidine (VCA); 28 days per cycle × at least 2 cycles； 1) chidamide 30mg biw × 2weeks；2) venetoclax 200mg/d × 2 weeks 3) azacitidine 100mg/d d1-7	Drug: venetoclax combining chidamide and azacitidine (VCA); information already included in arm/group descriptions; Other Names: VCA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remission (CR) rate	CR was <5% marrow blasts by morphology	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1 year leukemia free survival (LFS)	Leukemia-free survival (LFS) is defined as survival without evidence of relapse from treatment initiation	1 year from treatment initiation
1year overall survival (OS)	Overall survival（OS）is defined as the time from treatment initiation to death from any cause.	1 year from treatment initiation
Adverse events	Adverse event is defined as any untoward medical occurrence associated with treatment	2 months
objective response rate (ORR)	ORR is defined as CR, CRi and PR. Partial remission (PR) is defined as a decrease of at least 50% in the percentage of blasts to 5 to 25% in the bone marrow aspirate and the normalization of blood counts.	2 months

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Xiamen University
• Collaborators: Fujian Cancer Hospital; Dongguan People's Hospital; Huizhou Municipal Central Hospital; Fujian Provincial Hospital; Jieyang People's Hospital; Zhangzhou manicipal hospital of Fujian Province
• Investigators: Principal Investigator: Bing Xu, The First Affiliated Hospital of Xiamen University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2022
• Primary Completion (Estimated): January 31, 2024
• Study Completion (Estimated): January 31, 2026

Study Registration Dates

• First Submitted: March 8, 2022
• First Submitted That Met QC Criteria: March 23, 2022
• First Posted (Actual): March 31, 2022

Study Record Updates

• Last Update Posted (Estimated): December 8, 2023
• Last Update Submitted That Met QC Criteria: December 7, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: refractory/relapsed acute myelogenous leukemia
• 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: FXMH-AML-001; ChiCTR2200056657 (Registry Identifier: Chinese clinical trial registry)

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