TyrosIne Kinase Inhibitors in Chronic Myeloid Leukemia: Efficacy and Tolerability. The TIKlet Study

• Status: Active, not recruiting
• Trial end date: 2021-11-30
• Target enrollment: 0
• Participant gender: All

Summary

Rationale

The pharmacokinetics of imatinib and nilotinib, two BCR/Abl tyrosine-kinase inhibitors (TKI), is variable among patients suffering from chronic myeloid leukemia (CML). Transmembrane transporters may play a pivotal role in interindividual variability in TKI disposition. Furthermore, minimum plasma concentrations (Cmin) higher than 1 mg/L could be associated with a higher likelihood of molecular and cytogenetic responses.

The TIKlet study is aimed at evaluating correlations among the pharmacogenetics, pharmacokinetics and treatment efficacy/tolerability of imatinib and nilotinib in CML patients.

1. PATIENTS AND METHODS

1.1. Patients

Patients affected by CML will be enrolled after the informed consent will be signed, according to the following inclusion criteria:

• patients of both sexes,

• age between 18 and 80 years,

• treated with imatinib or nilotinib,

• included in follow-up activities at the participating Hematology Divisions,

• able to give informed consent,

• with a proved compliance with the scheduled treatment.

The administration of other drugs will be allowed, being known the dose and duration of treatment, as well as smoking and herbal products.

Alterations in organ functions or physicochemical exams, body mass index >28 do not represent exclusion criteria.

1.2. Enrollment and follow-up visits

During enrollment visit:

• patients will be informed about the study, their signed informed consent form will be collected and an individual alphanumeric code will be assigned.

• Patients' data will be recorded within the individual case report form (CRF) and a blood sample will be obtained.

At follow-up visits, a blood sample will be collected for therapeutic drug monitoring (TDM) and patients' CRF will be updated.

1.3. Blood samples

After centrifugation, the resulting plasma will be collected for TDM. During the enrollment visit, an aliquot of whole blood will be collected for molecular analyses.

1.4 Laboratory analyses

TDM will be performed by high-performance liquid chromatography systems, then results will be evaluated by a population pharmacokinetic analysis. Single nucleotide polymorphisms will be investigated in the following genes: ABCB1, ABCG2, hOCT1, OCTN1, OATP1A2.

Finally, response to drugs, in terms of Major Molecular Response (MMR) and Complete Cytogenetic Response (CCyR), and tolerability will be evaluated. Any possible correlation among drug disposition, pharmacogenetics and treatment effects will be analyzed.

• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Pisa
• Treatments: Imatinib Mesylate

Criteria

Inclusion Criteria:

• Patients affected by chronic myeloid leukemia

• Age limits: 18-80 years

• Male and female patients

• Treatment with imatinib/nilotinib since at least 3 weeks

• Optimal adherence

• Signed informed consent

Exclusion Criteria:

• Age <18 or >80 years

• Poor adherence

• Inability to attend follow-up visits

• Lack of signed informed consent

Concomitant administration of other drugs will be allowed, but active pharmacological agents, their dose and duration of treatment should be recorded.

Smoking is not considered an exclusion criterium, but it should be noticed and recorded