Ponatinib in CML Patients in Chronic Phase

Recruiting

• Conditions: Chronic Myeloid Leukemia, Chronic Phase

• Registration Number: NCT06119269
• Lead Sponsor: University of Pisa

Brief Summary

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

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 U.O. Clinical Pharmacology and Pharmacogenetics of 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 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.

Study Timeline

• Study Start: 2023-08-02
• Study First Submitted: 2023-10-18
• Status Verified: 2023-11
• Study First Submitted QC: 2023-11-03
• Last Update Submitted: 2023-11-03
• Study First Posted: 2023-11-07
• Last Update Posted: 2023-11-07
• Primary Completion: 2024-01-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Ponatinib plasma concentrations	2 year	Plasma concentrations of ponatinib included in the therapeutic range (i.e., \>21 nM)

Secondary Outcome Measures

Name	Time	Method
Occurrence of adverse events/adverse drug reactions	Up to 2 year	Adverse events/Adverse drug reactions observed and registered during ponatinib administration
Molecular response	Up to 2 year	Plasma levels of BCR-ABl transcript

Trial Locations

Locations (5)

University of Naples Federico II - Unit of Hematology; 🇮🇹 Napoli, Italy

Ospedale S. Eugenio ASL 2 Roma; 🇮🇹 Roma, Italy

Policlinico Milano; 🇮🇹 Milano, Italy

Santa Chiara University Hospital; 🇮🇹 Pisa, Italy

University of Cagliari - Businco Hospital - Unit of Hematology and Bone Marrow Transplant; 🇮🇹 Cagliari, Italy