Therapeutic Drug Monitoring of Tyrosine Kinase Inhibitor in Patients With Chronic Myeloid Leukemia

Recruiting

• Conditions: Tyrosine Kinase Inhibitor; Pharmacokinetics; Therapeutic Drug Monitoring

• Registration Number: NCT05259228
• Lead Sponsor: National Taiwan University Hospital

Brief Summary

Chronic myeloid leukemia (CML) consists of 3 clinical stages including chronic phase, accelerated phase and blast crisis. Patients may only survive for few more days to weeks once the disease progresses to blast crisis, even though they might have been stable for several years in the chronic phase. The standard treatment, continuous use of tyrosine kinase inhibitors (TKIs), improves long-term survival, and even may help patients achieve complete remission. Four TKIs are reimbursed by National Health Insurance in Taiwan. Among them, imatinib, nilotinib as well as dasatinib, and ponatinib are the first, second and third generations of TKIs, respectively. Many factors influence the disease control of CML, such as TKI type, genetic mutation and medication adherence. Only 69% of patients followed their physicians' recommendations in a local survey. The medication adherence of TKIs was compromised based on several clinical studies domestically and worldwide due to the slow progression in the chronic phase. Patients might hold or decrease the dose of TKIs on their own when they suffer side effects. Furthermore, the significant intra-subject variations of TKI plasma concentration and drug-drug and drug-food interactions which alter the metabolism of TKIs may lessen therapeutic effect and patient safety. Therefore, this study aims to develop and validate analytic methods of imatinib, dasatinib, nilotinib and ponatinib plasma concentrations. The investigators plan to build the pharmacokinetic models of these 4 TKIs and analyze the impacts of meals, adherence, hepatic enzyme inhibitors and inducers, antacids, proton pump inhibitors and H2 blockers, etc. Adverse drug reactions and treatment outcomes will be evaluated to determine the availability and feasibility of therapeutic drug monitoring of TKIs as part of routine service in pharmacist-led clinics.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2022-02-08
• Study First Submitted QC: 2022-02-17
• Study First Posted: 2022-02-28
• Study Start: 2022-12-01
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-17
• Last Update Posted: 2023-09-21
• Primary Completion: 2025-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Adult patients (≥ 20 year-old)
2. Patients who meet the above criteria and have already initiated or are going to receive imatinib, dasatinib, nilotinib, or ponatinib treatment at National Taiwan University Hospital/National Taiwan University Cancer Center from September 2022 to December 2025

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Exclusion Criteria

1. Patients who are unable to cooperate with blood drawing
2. Patients who have not submit the informed consent

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Analytic methods of TKI plasma concentrations	September, 2022 to December, 2025	To develop and validate analytic methods of imatinib, dasatinib, nilotinib and ponatinib plasma concentrations.
Minimum plasma concentration [Cmin] of TKI	September, 2022 to December, 2025	To measure the minimum plasma concentrations of imatinib, dasatinib, nilotinib and ponatinib.
Patient adherence of TKI treatment	September, 2022 to December, 2025	To follow up and record the adherence of imatinib, dasatinib, nilotinib and ponatinib of each patient.
Analysis of drug-drug interactions	September, 2022 to December, 2025	To analyze the impacts of hepatic enzyme (CYP) inhibitors and inducers, antacids, proton pump inhibitors and H2 blockers on the concentration of imatinib, dasatinib, nilotinib and ponatinib.
Adverse drug reactions and treatment outcomes of TKI	September, 2022 to December, 2025	To evaluate the adverse drug reactions and treatment outcomes in order to determine the availability and feasibility of therapeutic drug monitoring of TKIs as part of routine service in pharmacist-led clinics.

Trial Locations

Locations (1)

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan