Screening of IDH1 and IDH2 Gene Mutations in Adult Acute Myeloid Leukemia for Possible Targeted Therapy

NCT ID: NCT03499912

Last Updated: 2018-04-20

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 300 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-03-29
• Study Completion Date: 2019-07-01

Brief Summary

1. To assess the incidence of IDH1 and IDH2 mutations in adult AML patients, and to explore their associations with the patients' clinical, cytogenetic, and molecular characteristics as well as with treatment response and outcome.

2. To delineate the similarities and distinctions among mutations at IDH1-R132, IDH2-R140 and IDH2-R172 in AML, both clinically and molecularly (including cytogenetics, immunophenotyping, mutation co-occurrence patterns).

3. The results can be references for future selection of targeted therapy (targeting IDH mutant proteins).

Detailed Description

Isocitrate dehydrogenases (IDH) are enzymes that catalyze oxidative decarboxylation of isocitrate into alpha-ketoglutarate (α-KG). IDH1 and IDH2 mutations in AML give the enzymes neomorphic enzymatic activity to transform α-KG to D-2HG, an oncometabolite which acts as a competitive inhibitor of dioxygenases, and causes dysregulation of TET2 and histone demethylases, consequently leading to epigenetic reprogramming of a cell, blocking differentiation and contributing to a transformed phenotype, and leukemogenesis. Investigators plan to recruit 300 adult AML patients (newly diagnosed or relapsed). 10mL of peripheral blood or marrow blood will be obtained from routine practice blood/marrow sampling specimens (no extra venipuncture or bone marrow aspiration would be required) and sent for routine tests such as cytogenetics, immunophenotyping, and gene mutation analyses. IDH1 R132, IDH2 R140, and IDH2 R172 mutations will be screened by PCR followed by Sanger sequencing, as previously described.

Investigators will first assess the incidence of IDH1 and IDH2 mutations in adult AML patients, and then explore their associations with the patients' clinical course, cytogenetic, and molecular characteristics as well as with treatment response and outcome. Investigators also seek to delineate the similarities and distinctions among IDH mutation variants at IDH1-R132, IDH2-R140 and IDH2-R172, both clinically and molecularly (including cytogenetics, immunophenotyping, mutation co-occurrence patterns).

Conditions

Acute Myeloid Leukemia

Study Design

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

Eligibility Criteria

Inclusion Criteria

1. Patients ≥20 Years with Diagnosed Acute Myeloid Leukemia

2. Willing to provide voluntary written informed consent before study related procedures

Exclusion Criteria

1. Not acute myeloid leukemia patients

2. Patients <20 Years with Diagnosed Acute Myeloid Leukemia

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Taiwan University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wen-Chien Chou

Role: PRINCIPAL_INVESTIGATOR

National Taiwan University Hospital

Locations

National Taiwan University Hospital

Taipei, , Taiwan

Site Status: RECRUITING

Countries

Taiwan

Central Contacts

Wen-Chien Chou

Role: CONTACT

wchou@ntu.edu.tw

0972651701

Ming-Kai Chuang

Role: CONTACT

mingkai@ntuh.gov.tw

0972652258

Facility Contacts

Wen-Chien Chou

Role: primary

wchou@ntu.edu.tw

0972651701

Other Identifiers

201701030RIPC

Identifier Type: -

Identifier Source: org_study_id