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

NCT01860456 · Status: COMPLETED · Type: OBSERVATIONAL · Enrollment: 412

Last updated 2025-06-05

No results posted yet for this study

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.

Conditions

  • Chronic Myeloid Leukemia

Interventions

DRUG

Imatinib/Nilotinib

Imatinib: 400 mg/day oral - Nilotinib: 600-800 mg/day oral

Sponsors & Collaborators

  • University of Pisa

    lead OTHER

Principal Investigators

  • Sara Galimberti, MD, PhD · Department of Clinical and Experimental Medicine, University of Pisa

  • Antonello Di Paolo, MD, PhD · Department of Clinical and Experimental Medicine, University of Pisa

Eligibility

Min Age
18 Years
Max Age
80 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2013-05-31
Primary Completion
2024-12-31
Completion
2024-12-31

Countries

  • Italy

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT01860456 on ClinicalTrials.gov