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

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)

Overview

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

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.

Interventions

• Drug venetoclax combining chidamide and azacitidine (VCA)
  information already included in arm/group descriptions

Primary outcome measures

• Complete remission (CR) rate [Time frame: 2 months]
• Overall response rate (ORR) [Time frame: 2 months]

Secondary outcome measures (3)

• 1 year leukemia free survival (LFS) [Time frame: 1 year from treatment initiation]
• 1year overall survival (OS) [Time frame: 1 year from treatment initiation]
• Adverse events [Time frame: 2 months]

Eligibility criteria

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:

• Creatinine clearance≥30 mL/min and serum Creatinine ≤ 160µmol/L
• ALT and AST ≤ 3 × upper limit of normal (ULN)
• 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:

• 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);
• 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);
• 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);
• History of uncontrolled angina pectoris or myocardial infarction within 6 months prior to Screening;
• History of New York Heart Association Class 3 or 4 heart failure;
• Complete left bundle branch block;
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Bing Xu — Xiamen

Identifiers

NCT: NCT05305859 · FXMH-AML-001 · ChiCTR2200056657

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)
• ChiCTR ChiCTR2200056657 (Chinese Clinical Trial Registry)

View this study on ClinicalTrials.gov ↗