Clinical Research for Azacitidine Combined With Low-dose Dasatinib in Maintenance Therapy of Acute Myeloid Leukemia

• Status: Recruiting
• Trial end date: 2023-12-15
• Target enrollment: 0
• Participant gender: All

Summary

This project is a prospective, single-center study to evaluate the efficacy, safety and related mechanisms of azacitidine combined with low-dose dasatinib in maintenance therapy in patients with intermediate and high-risk acute myeloid leukemia(AML). The patients were randomly divided into azacitidine group and azacitidine combined with low-dose dasatinib group. The overall survival and disease-free survival were taken as the main end points, and the mortality and recurrence rate were taken as the secondary end points, meanwhile, the incidence of adverse events were evaluated. At the same time, the mRNA expressions of DNA methyltransferase (DNMT1, DNMT3a, DNMT3b), tumor suppressor genes (TP53, P15, P16, P21, CDH1, DOK6, SHP1, PTPN11) and differentiation genes (pu.1, C/EBP α, C/EBP β) were detected. Pyrophosphate sequencing was used to detect the methylation level of the promoter region of these tumor suppressor genes. Western Blot was used to detect apoptosis proteins (caspase3, caspase8) and phosphorylated proteins (pSTAT3, pSTAT5, pAKT). The proportion of apoptotic population of bone marrow cells was determined by flow cytometry. Therefore, the data in this study will reflect the efficacy and safety of azacitidine or azacitidine combined with low-dose dasatinib in real-world maintenance therapy in patients with medium and high-risk AML.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: LanZhou University
• Collaborator: Beijing Health Alliance Charitable Foundation
• Treatments: Azacitidine; Dasatinib

Criteria

Inclusion Criteria:

1. Patients with intermediate and high-risk AML who are diagnosed according to the 2016 WHO guidelines, aged ≥18 years;

2. Detect minimal residual disease(-) after induction therapy and consolidation therapy;

3. Eastern Cooperative Oncology Group (ECOG) performance status score 0-2;

4. The heart, pulmonary, liver and kidneys have sufficient organ functions:

1. Cardiac color doppler ultrasound shows cardiac ejection fraction> 50%, heart function classification NYHA III/IV, no heart block or arrhythmia;

2. Patients without severe restrictive/obstructive pulmonary disease;

3. Liver function: total bilirubin (TBIL) < 2 times the upper limit of normal, alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) <2.5 times the upper limit of normal;

4. Renal function: serum creatinine (Cr) < 1.5 times the upper limit of normal.

5. The patient and family members agree and sign an informed consent form.

Exclusion Criteria:

1. Patients with malignant tumors of other organs;

2. HCV positive; or HIV positive; or one of the following HBV test results:

1. HBsAg positive;

2. HBsAg negative, HBcAb positive and HBV DNA titer positive;

3. Pregnant and lactating women, and patients who have family planning during the enrollment period;

4. Patients considered to be unsuitable for enrollment by the investigator.