Clinical trial NCT03537560: Detection of IDH2 Mutations and Monitoring Molecular Residual Disease in Patients With AML
Official title: Detection of IDH2 Mutations and Monitoring Molecular Residual Disease in Patients With Acute Myeloid Leukemia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Myeloid Leukemia
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
First posted: 2018-05-25
Enrollment: 334
Sex: ALL
Minimum age (years): 20
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients with AML newly diagnosed and followed in Chang Gung Memorial Hospital.

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.

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

Primary outcomes:
measure: Detection of IDH2 mutations
timeFrame: 1 month
Secondary outcomes:
measure: Follow-up detection of IDH2 mutations
timeFrame: 24 months
Other outcomes:
Locations:
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital-Linkou
state: State
Study officials:
affiliation: Chang Gung Memorial Hospital
name: Lee-Yung Shih, MD
role: PRINCIPAL_INVESTIGATOR
References: