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

Sponsor
The First Affiliated Hospital of Xiamen University (Other)
Overall Status
Recruiting
CT.gov ID
NCT05305859
Collaborator
Fujian Provincial Hospital (Other), Fujian Cancer Hospital (Other), Zhangzhou manicipal hospital of Fujian Province (Other), Jieyang People's Hospital (Other), Dongguan People's Hospital (Other), Huizhou Municipal Central Hospital (Other)
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Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
  • Drug: venetoclax combining chidamide and azacitidine (VCA)
Phase 2

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 Design

Study Type:
Interventional
Anticipated Enrollment :
30 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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)
Actual Study Start Date :
Apr 1, 2022
Anticipated Primary Completion Date :
Jan 31, 2024
Anticipated Study Completion Date :
Jan 31, 2026

Arms and Interventions

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
  • Outcome Measures

    Primary Outcome Measures

    1. Complete remission (CR) rate [2 months]

      CR was <5% marrow blasts by morphology

    Secondary Outcome Measures

    1. 1 year leukemia free survival (LFS) [1 year from treatment initiation]

      Leukemia-free survival (LFS) is defined as survival without evidence of relapse from treatment initiation

    2. 1year overall survival (OS) [1 year from treatment initiation]

      Overall survival(OS)is defined as the time from treatment initiation to death from any cause.

    3. Adverse events [2 months]

      Adverse event is defined as any untoward medical occurrence associated with treatment

    4. objective response rate (ORR) [2 months]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Bing Xu Xiamen Fujian China 361003

    Sponsors and Collaborators

    • The First Affiliated Hospital of Xiamen University
    • Fujian Provincial Hospital
    • Fujian Cancer Hospital
    • Zhangzhou manicipal hospital of Fujian Province
    • Jieyang People's Hospital
    • Dongguan People's Hospital
    • Huizhou Municipal Central Hospital

    Investigators

    • Principal Investigator: Bing Xu, The First Affiliated Hospital of Xiamen University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    The First Affiliated Hospital of Xiamen University
    ClinicalTrials.gov Identifier:
    NCT05305859
    Other Study ID Numbers:
    • FXMH-AML-001
    • ChiCTR2200056657
    First Posted:
    Mar 31, 2022
    Last Update Posted:
    Aug 2, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by The First Affiliated Hospital of Xiamen University
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 2, 2022