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

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03499912
• Other study ID #: 201701030RIPC
• Status: Recruiting
• First received: March 22, 2018
• Last updated: April 18, 2018
• Start date: March 29, 2017
• Est. completion date: July 1, 2019

Study information

• Verified date: March 2018
• Source: National Taiwan University Hospital
• Contact: Wen-Chien Chou
• Phone: 0972651701
• Email: wchou[@]ntu.edu.tw
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: July 1, 2019
• Est. primary completion date: April 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Locations

Country	Name	City	State
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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