Detection of IDH2 Mutations and Monitoring Molecular Residual Disease in Patients With AML

NCT ID: NCT03537560

Last Updated: 2023-08-31

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 334 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-03-01
• Study Completion Date: 2023-07-31

Brief Summary

1. Detection of IDH2 mutations in AML patients to define it incidence and correlation with clinical characteristics, relapse-free and overall survival.

2. Identify AML patients who are potential candidates for IDH2 inhibitor treatment.

3. Monitoring minimal residual disease (MRD) following therapy to evaluate its possible role in the strategy of MRD-directed therapy in the future in patients carrying IDH2 mutations at initial diagnosis.

Detailed Description

Isocitrate dehydrogenase 2 (IDH2) was found to be one of the recurrently mutated genes in acute myeloid leukemia, indicating its critical role in leukemogenesis. IDH2 mutations account for about 10%-20% of AML patients. IDH2 mutation is found to be associated with production of 2-HG, which interferes with histone methylation and DNA modification, results in partial block of myeloid cell differentiation. IDH inhibitors have shown in preclinical model to reverse differentiation blockage in tumor cells. The assessment of IDH2 inhibitors is ongoing with phase I/II clinical trials. The analysis of IDH2 mutation in AML patients will help to identify AML patients who might benefit from IDH inhibitor treatment.

Bone marrow samples from 300 adult patients (>20 years old) with newly diagnosed AML since 2014/1/1 and received standard chemotherapy in hospitals which has jointed Ministry of Health and Welfare AML program will be examined. The mononuclear cells are extracted from bone marrow samples at the initial diagnosis. The mutational analysis of exon 4 of IDH2 gene will be performed by PCR amplication followed by pyrosequencing to detect IDH2-R140 and R172 mutations and mutant levels. Follow-up samples of patients carrying IDH2 mutations at the time of achieving hematologic remission, subsequent samples during different time points including at least following two post-remission chemotherapy, at the end of therapy and every 3 months thereafter in the first year and then every 6 months up to 24 months, as well as at time of relapse, will be measured by LNA-quantitative real-time PCR with TaqMan probe assay to determine the changes of IDH2 mutant levels.

Conditions

Acute Myeloid Leukemia

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• Patients diagnosed with AML, age ≥ 20 years, and are willing to sign the informed consent

Exclusion Criteria

• Not AML patients
• Patients diagnosed with AML but age < 20 years

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chang Gung Memorial Hospital

OTHER

Sponsor Role: lead

Responsible Party

Lee-Yung Shih

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lee-Yung Shih, MD

Role: PRINCIPAL_INVESTIGATOR

Chang Gung Memorial Hospital

Locations

Chang Gung Memorial Hospital-Linkou

Taoyuan District, State, Taiwan

Countries

Taiwan

Other Identifiers

201700154B0

Identifier Type: -

Identifier Source: org_study_id