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

NCT05042531 | Unknown

• 2 other identifiers: AZALDDASA3ChiCTR2100042418
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Myeloid Leukemia

Keywords

AML,Maintenance Therapy,Azacitidine,Dasatinib

Outcome Measures

Primary Outcomes (2)

• overall survival

  OS is defined as the time from the date of enrollment until the date of death from any cause.

  up to 30 months.

• disease-free survival

  Event-free survival is defined as the time from enrollment until documented refractory disease, relapse after complete remission(CR) or CR with incomplete recovery of blood counts(CRi), or death from any cause.

  up to 30 months.

Secondary Outcomes (7)

• mortality

  mortality rate at 30 months.

• recurrence rate

  recurrence rate at 30 months.

• adverse events

  Adverse events were assessed weekly during the first and second cycles, and every two cycles thereafter (each cycle is 28 days), up to 30 months.

• apoptotic protein and phosphorylated protein

  once before enrollment and once after the completion of the study, up to 30 months.

• DNA methyltransferase, tumor suppressor genes and differentiation genes

  once before enrollment and once after the completion of the study, up to 30 months.

Study Arms (2)

experimental group

EXPERIMENTAL

Patients with intermediate and high risk AML were negative for minimal residual disease after intensive induction and consolidation chemotherapy,the patients were randomly divided into two groups, and one group was given azacitidine(75mg/m2, per day on day 1-7\]. Dasatinib 100 mg p.o. qd was administered on days 1-28 of each consolidation cycle.

Drug: Azacitidine; Drug: Dasatinib

control group

ACTIVE COMPARATOR

Patients with intermediate and high risk AML were negative for minimal residual disease after intensive induction and consolidation chemotherapy,the patients were randomly divided into two groups, and the other group was given azacitidine(75mg/m2, per day on day 1-7)on days 1-28 of each consolidation cycle.

Drug: Azacitidine

Interventions

Azacitidine DRUG

Azacitidine, 75mg/m2,d1-7;Treatment cycles every 28 days

control group; experimental group

Dasatinib DRUG

dasatinib,20mg,po,qd,treatment cycles every 28 days

experimental group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with intermediate and high-risk AML who are diagnosed according to the 2016 WHO guidelines, aged ≥18 years;
• Detect minimal residual disease(-) after induction therapy and consolidation therapy;
• Eastern Cooperative Oncology Group (ECOG) performance status score 0-2;
• The heart, pulmonary, liver and kidneys have sufficient organ functions:
• Cardiac color doppler ultrasound shows cardiac ejection fraction\> 50%, heart function classification NYHA III/IV, no heart block or arrhythmia;
• Patients without severe restrictive/obstructive pulmonary disease;
• 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;
• Renal function: serum creatinine (Cr) \< 1.5 times the upper limit of normal.
• The patient and family members agree and sign an informed consent form.

You may not qualify if:

• Patients with malignant tumors of other organs;
• HCV positive; or HIV positive; or one of the following HBV test results:
• HBsAg positive;
• HBsAg negative, HBcAb positive and HBV DNA titer positive;
• Pregnant and lactating women, and patients who have family planning during the enrollment period;
• Patients considered to be unsuitable for enrollment by the investigator.

Sponsors & Collaborators

• LanZhou University: lead
• Beijing Health Alliance Charitable Foundation: collaborator

Study Sites (1)

The First Hospital of Lanzhou University

Lanzhou, Gansu, 730000, China

RECRUITING

Related Publications (18)

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MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Azacitidine; Dasatinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Thiazoles; Sulfur Compounds; Azoles

Study Officials

• Bei Liu, MD

  The First Hospital of Lanzhou University,Lanzhou,Gansu,China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bei Liu, MD

CONTACT

+86 13809319379; liubeiff@163.com

Long Zhao

CONTACT

+18919128021; dragonzhao@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: According to the random number table
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician, Clinical Associate Professor，Deputy Director of Hematology Department

Model Details: The patients were randomly divided into two groups among intermediate and high-risk AML, namely azacitidine group, azacitidine combined with low-dose dasatinib group, with overall survival and disease-free survival as the main research endpoints , taking mortality and recurrence rates as secondary research endpoints, assessing the incidence of adverse events, and studying its related mechanisms.

Study Record Dates

• First Submitted: September 1, 2021
• First Posted: September 13, 2021
• Study Start: November 13, 2021
• Primary Completion: September 1, 2023
• Study Completion: December 15, 2023
• Last Updated: April 25, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)