PHOENICS: Ponatinib in CML Patients in Chronic Phase

Sponsor

University of Pisa (Other)

Overall Status

Recruiting

CT.gov ID

NCT06119269

Collaborator

(none)

100

Enrollment

Locations

Anticipated Duration (Months)

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloid Leukemia, Chronic Phase	Diagnostic Test: Therapeutic drug monitoring Diagnostic Test: Molecular Response

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 Design

Study Type:

Observational

Anticipated Enrollment :

100 participants

Observational Model:

Cohort

Time Perspective:

Retrospective

Official Title:

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

Actual Study Start Date :

Aug 2, 2023

Anticipated Primary Completion Date :

Jan 31, 2024

Anticipated Study Completion Date :

Dec 31, 2024

Outcome Measures

Primary Outcome Measures

Ponatinib plasma concentrations [2 year]
Plasma concentrations of ponatinib included in the therapeutic range (i.e., >21 nM)

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Patients will be enrolled according the following 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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	University of Cagliari - Businco Hospital - Unit of Hematology and Bone Marrow Transplant	Cagliari	Italy	09124
2	Policlinico Milano	Milano	Italy	20122
3	University of Naples Federico II - Unit of Hematology	Napoli	Italy	80131
4	Santa Chiara University Hospital	Pisa	Italy	56126
5	Ospedale S. Eugenio ASL 2 Roma	Roma	Italy	00144