Ignite Creation Date:
2024-05-06 @ 4:37 PM
Last Modification Date:
2024-10-26 @ 2:13 PM
Study NCT ID:
NCT05042531
Status:
UNKNOWN
Last Update Posted:
2022-04-25
First Post:
2021-09-01
Brief Title:
Clinical Research for Azacitidine Combined With Low-dose Dasatinib in Maintenance Therapy of Acute Myeloid Leukemia
Sponsor:
LanZhou University
Organization:
LanZhou University
Study Overview
Official Title:
Clinical Research for Azacitidine Combined With Low-dose Dasatinib in Maintenance Therapy of Acute Myeloid Leukemia
Status:
UNKNOWN
Status Verified Date:
2022-04
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 leukemiaAML 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 pu1 CEBP α CEBP 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
Detailed Description:
In addition to studying the overall survival disease-free survival and recurrence rates mortality and incidence of adverse events of patients treated with azacitidine or azacitidine combined with low-dose dasatinib we will also study its related mechanisms One of the pathogenesis of AML is that abnormal DNA methylation makes the cell cycle out of control and carcinogenesis by inhibiting the expression of tumor suppressor genes In addition the abnormal activation of tyrosine kinase signal pathway also promotes the development of leukemia Azacitidine the hypomethylating agents can not only inhibit the DNA methyltransferase family but also activate tumor suppressor genes to inhibit a variety of tyrosine kinase signaling pathways including JAK-STAT NaShen et al have directly demonstrated that tyrosine kinase inhibitors TKIs can not only inhibit the abnormal activation of tyrosine kinase pathway but also reduce DNA methylation This study found that the combination of the second generation TKIs and hypomethylating agents can reduce has a synergistic effect on promoting apoptosis and reducing DNA methylation In addition TKIs often produces drug resistance due to long exposure time and the main mechanisms of drug resistance is due to DNA methylation and abnormal reactivation of tyrosine kinase signal pathway The combination of TKI and azacitidine reduces DNA methylation and inhibits the reactivation of abnormal tyrosine kinase signal pathway which is helpful to improve TKI drug resistance Based on the above theory we assume that patients treated with azacitidine and dasatinib may have more obvious demethylation effect increased expression of tumor suppressive genes more obvious apoptosis and inhibition of phosphorylated protein expressionSo we did the lab tests of these mechanismsWe innovatively used azacitidine and TKIs in the treatment of patients with AML maintenance in order to reduce drug toxicity enhance drug efficacy improve patient prognosis and reduce the financial burden of patients
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| ChiCTR2100042418 | REGISTRY | Chinese Clinical Trial Registry | None |