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

Pharmacokinetics Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05259228
• Other study ID #: 202008067RIND
• Status: Recruiting
• Start date: December 1, 2022
• Est. completion date: December 2025

Study information

• Verified date: September 2023
• Source: National Taiwan University Hospital
• Contact: Shu-Wen Lin, PharmD, MS
• Phone: 02 - 33668782
• Email: shuwenlin[@]ntu.edu.tw
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Exclusion Criteria:

1. Patients who are unable to cooperate with blood drawing

2. Patients who have not submit the informed consent

Related Conditions & MeSH terms

• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Pharmacokinetics
• Therapeutic Drug Monitoring
• Tyrosine Kinase Inhibitor

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	Analytic methods of TKI plasma concentrations	To develop and validate analytic methods of imatinib, dasatinib, nilotinib and ponatinib plasma concentrations.	September, 2022 to December, 2025
Primary	Minimum plasma concentration [Cmin] of TKI	To measure the minimum plasma concentrations of imatinib, dasatinib, nilotinib and ponatinib.	September, 2022 to December, 2025
Primary	Patient adherence of TKI treatment	To follow up and record the adherence of imatinib, dasatinib, nilotinib and ponatinib of each patient.	September, 2022 to December, 2025
Primary	Analysis of drug-drug interactions	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.	September, 2022 to December, 2025
Primary	Adverse drug reactions and treatment outcomes of TKI	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.	September, 2022 to December, 2025