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

Xiamen University

Status and phase

Enrolling

Phase 2

Conditions

Relapsed Adult AML

Refractory Leukemia

Leukemia, Myeloid, Acute

Treatments

Drug: venetoclax combining chidamide and azacitidine (VCA)

Study type

Interventional

Funder types

Other

Identifiers

NCT05305859

ChiCTR2200056657 (Registry Identifier)

FXMH-AML-001

Details and patient eligibility

About

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

Full 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.

Enrollment

30 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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