NCT06119269

Ponatinib in Chronic Myeloid Leukemia Patients in Chronic Phase

Ponatinib in cHronic myelOid LEukemia patieNts In Chronic phaSe: the PHOENICS Protocol

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 100 (estimated)
• Sponsor: University of Pisa · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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 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

• Chronic Myeloid Leukemia, Chronic Phase

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	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)
DIAGNOSTIC_TEST	Molecular Response	BCR-ABl transcript levels will be assessed to evaluate molecular response to ponatinib

Timeline

• Start date: 2023-08-02
• Primary completion: 2025-12-31
• Completion: 2025-12-31
• First posted: 2023-11-07
• Last updated: 2025-06-05

Locations

5 sites across 1 country: Italy