Ponatinib in Chronic Myeloid Leukemia Patients in Chronic Phase

NCT ID: NCT06119269

Last Updated: 2025-06-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

100 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-08-02

Study Completion Date

2025-12-31

Brief Summary

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The goal of this retrospective observational study is to evaluate any possible association between plasma concentrations of ponatinib and its pharmacodynamics (efficacy/tolerability) in patients affected by chronic myeloid leukemia in chronic phase (CML-CP).

In particular, the aims of the study will be:

* primary aim: to investigate the relationships (if any) between plasma concentrations and activity/toxicity of ponatinib in a population of CML-CP patients enrolled in several Italian hematological centers;
* secondary aim: to set up an algorithm aimed at helping physicians to improve drug dosing based on several variables (i.e., plasma drug concentrations, tolerability, molecular response to therapy).

The study will enroll CML-CP patients who were exposed to ponatinib as second, third or fourth line of chemotherapy.

Detailed Description

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The study protocol is a non-interventional, retrospective observational study which involves the collection of data from medical records relating to the plasma dosages of ponatinib performed as per clinical practice, all carried out at the pharmacokinetics laboratory of the Unit of Clinical Pharmacology and Pharmacogenetics of Azienda Ospedaliero Universitaria Pisana (AOUP). These data will be collected in CRF and will be correlated to efficacy data (extent of molecular response) and toxicity of ponatinib (haematological, extra-haematological adverse events, together with adverse event severity). Real-life experience (dosage adjustments made by clinicians based on plasma dosage) will be used to propose an algorithm that can help in choosing the correct dosage of ponatinib.

Classical statistical analyses (for descriptive and comparison aims) will be used according to their appropriateness. Moreover, factors affecting the pharmacokinetics (PK) of ponatinib will be investigated by nonlinear mixed effect modeling adopting the MONOLIX 2021R2 suite. Final model will be used as parte of the dosing algorithm.

Notably, all clinical and laboratory data will be anonymized to protect patients' privacy, and harvested in a database that will be used to perform pharmacometric and statistical analyses.

Conditions

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Chronic Myeloid Leukemia, Chronic Phase

Study Design

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Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Interventions

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Therapeutic drug monitoring

At each follow up visit, plasma concentrations of ponatinib will be measured and compared with therapeutic range (according to a lower concentration equal to 21 nM)

Intervention Type DIAGNOSTIC_TEST

Molecular Response

BCR-ABl transcript levels will be assessed to evaluate molecular response to ponatinib

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Subjects ≥18 years old affected by CML
* Patients being treated with ponatinib at a dose of 45, 30 or 15 mg/day for more than 14 days
* Patients who have provided informed consent to the study

Exclusion Criteria

* Subjects \<18 years old
* Patients who did not provide an informed consent to the study

The co-administration of drugs other than ponatinib will not be considered an exclusion criterium, but all of the drugs will be registered (together with daily doses and duration of treatment) as possible factors of ponatinib PK variability.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Pisa

OTHER

Sponsor Role lead

Responsible Party

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Antonello Di Paolo, M.D., Ph.D.

Professor of Pharmacology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Sara Galimberti, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Pisa - Dept. Clinical and Experimental Medicine

Locations

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University of Cagliari - Businco Hospital - Unit of Hematology and Bone Marrow Transplant

Cagliari, , Italy

Site Status RECRUITING

Policlinico Milano

Milan, , Italy

Site Status RECRUITING

University of Naples Federico II - Unit of Hematology

Napoli, , Italy

Site Status RECRUITING

Santa Chiara University Hospital

Pisa, , Italy

Site Status RECRUITING

Ospedale S. Eugenio ASL 2 Roma

Roma, , Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Sara Galimberti, PhD

Role: CONTACT

+39 050 993111 ext. 3488

Claudia Baratè, MD

Role: CONTACT

+39 050 992111

Facility Contacts

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Giovanni Caocci, PhD

Role: primary

+39 070 5296 ext. 2065

Alessandra Iurlo, MD

Role: primary

+39 02 5503.1 ext. 3422

Luigia Luciano, MD

Role: primary

+39 081 746 ext. 2165

Sara Galimberti, PhD

Role: primary

+39 050 993111 ext. 3488

Claudia Baratè, MD

Role: backup

+39 050 992111

Elisabetta Abruzzese, MD

Role: primary

+39 06 51001

References

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Galimberti S, Abruzzese E, Luci G, Barate C, Luciano L, Iurlo A, Caocci G, Morganti R, Stefanelli F, Di Paolo A. A New Algorithm Integrating Molecular Response, Toxicity, and Plasma Level Measures for Ponatinib Dose Choice in Patients Affected by Chronic Myeloid Leukemia. Pharmaceutics. 2024 Mar 11;16(3):383. doi: 10.3390/pharmaceutics16030383.

Reference Type RESULT
PMID: 38543276 (View on PubMed)

Other Identifiers

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23707

Identifier Type: -

Identifier Source: org_study_id

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