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

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).

Study Overview

• Status: Unknown
• Conditions: Acute Myeloid Leukemia

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).

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Wen-Chien Chou; Phone Number: 0972651701; Email: wchou@ntu.edu.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult AML patients (newly diagnosed or relapsed) diagnosed at the National Taiwan University Hospital (NTUH) according to the updated 2016 WHO AML classification criteria.

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of IDH1 and IDH2 mutation	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.	2017/03/07 - 2019/03/01

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Wen-Chien Chou, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2017
• Primary Completion (Anticipated): April 1, 2019
• Study Completion (Anticipated): July 1, 2019

Study Registration Dates

• First Submitted: March 22, 2018
• First Submitted That Met QC Criteria: April 13, 2018
• First Posted (Actual): April 17, 2018

Study Record Updates

• Last Update Posted (Actual): April 20, 2018
• Last Update Submitted That Met QC Criteria: April 18, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Prognosis; Acute myeloid leukemia; IDH1; Genetic mutations; IDH2
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: 201701030RIPC