Effect of Pharmacogenetics on Imatinib Plasma Level and Response

NCT03262974 | Completed

• 1 other identifier: Imatinib Pharmacogenetics
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Imatinib, the tyrosine kinase inhibitor, is used for treatment of Philadelphia positive chronic myeloid leukemia. Despite its efficacy and favorable pharmacokinetic profile, there is a large inter-individual variability in imatinib plasma concentrations, which may lead to treatment failure and disease progression. Polymorphisms in genes related to absorption, distribution, metabolism and excretion of imatinib may affect the bioavailability and consequently the response to the drug. The study aims to investigate the possible effect of genetic polymorphisms in certain metabolizing enzymes \[CYP3A5\*3 (rs776746), CYP2C8\*3 (rs11572080 and rs10509681)\] and membrane transporters \[ABCB1 2677G\>T/A (rs2032582) and SLC22A1 1222A \> G (rs628031)\] by PCR on the plasma level (by HPLC-UV) and molecular response (MMR) of imatinib in patients with CML. The study also aims to provide CML patients with a personalized treatment option, thereby probably improving the response and reducing the side effects.

Conditions

Chronic Myeloid Leukemia

Keywords

Imatinib; Pharmacogenetics; CML; Plasma level

Outcome Measures

Primary Outcomes (1)

• Major molecular response to imatinib

  A major molecular response (MMR) to imatinib therapy is defined as a BCR-ABL1 RNA level ≤ 0.1% on the International Scale (a consensus standardized measurement scale intended to allow direct comparison of BCR-ABL1 RNA levels in any laboratory adopting its use). The International Scale was specifically designed so that, by definition, 100% is the median pretreatment baseline level of BCR-ABL1 RNA in early chronic phase CML and a 1,000-fold reduction from baseline is defined as 0.1% (MMR) (Press,

  12 months from starting the drug

Study Arms (2)

CML patients with MMR

CYP3A5\*3 , CYP2C8\*3 , ABCG2 421 C\>A and SLC22A1 1222A \> G SNPs on the plasma level by HPLC-UV and molecular response of imatinib by PCR

Diagnostic Test: PCR; Diagnostic Test: HPLC-UV

CML patients without MMR

CYP3A5\*3 , CYP2C8\*3 , ABCG2 421 C\>A and SLC22A1 1222A \> G SNPs on the plasma level by HPLC-UV and molecular response of imatinib by PCR

Diagnostic Test: PCR; Diagnostic Test: HPLC-UV

Interventions

PCR DIAGNOSTIC_TEST

PCR

CML patients with MMR; CML patients without MMR

HPLC-UV DIAGNOSTIC_TEST

HPLC-UV

CML patients with MMR; CML patients without MMR

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

CML patients treated at Medical Oncology Department, South Egypt Cancer Institute (SECI), Assiut. Egypt.

You may qualify if:

• Documented hematological, cytogenetic and molecular diagnosis of Philadelphia positive CML
• Imatinib treatment for at least 12 months

You may not qualify if:

• Poor compliance to treatment
• identification of gene mutation(s) in the kinase domain of BCR- ABL1.

Sponsors & Collaborators

• Assiut University: lead

Study Sites (1)

South Egypt Cancer Institute

Asyut, Egypt

Location

Biospecimen

Retention: SAMPLES WITH DNA

DNA will be extracted from blood samples and frozen at -80 for further analysis

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Safwat Mangoura

  Pharmacology department, Faculty of Medicine, Assiut University

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant lecturer

Study Record Dates

• First Submitted: August 24, 2017
• First Posted: August 28, 2017
• Study Start: October 29, 2017
• Primary Completion: October 1, 2023
• Study Completion: October 1, 2023
• Last Updated: October 27, 2023

Record last verified: 2023-10

Locations

EG (1)