Clinical trial NCT05259228: Therapeutic Drug Monitoring of Tyrosine Kinase Inhibitor in Patients With Chronic Myeloid Leukemia
Official title: Therapeutic Drug Monitoring of Tyrosine Kinase Inhibitor in Patients With Chronic Myeloid Leukemia
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Tyrosine Kinase Inhibitor
Pharmacokinetics
Therapeutic Drug Monitoring
Keywords: tyrosine kinase inhibitor
pharmacokinetics
therapeutic drug monitoring
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2022-02-28
Enrollment: 40
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients (≥ 20 year-old) who 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.

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.


Eligibility criteria: 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

Primary outcomes:
measure: Analytic methods of TKI plasma concentrations
timeFrame: September, 2022 to December, 2025
measure: Minimum plasma concentration [Cmin] of TKI
timeFrame: September, 2022 to December, 2025
measure: Patient adherence of TKI treatment
timeFrame: September, 2022 to December, 2025
measure: Analysis of drug-drug interactions
timeFrame: September, 2022 to December, 2025
measure: Adverse drug reactions and treatment outcomes of TKI
timeFrame: September, 2022 to December, 2025
Secondary outcomes:
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: Graduate Institute of Clinical Pharmacy, National Taiwan University
name: Shu-Wen Lin, PharmD, MS
role: PRINCIPAL_INVESTIGATOR
References: