Ponatinib in Chronic Myeloid Leukemia Patients in Chronic Phase
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Therapeutic drug monitoring, Molecular Response.
- Who it may be relevant to
- Registry conditions: Chronic Myeloid Leukemia, Chronic Phase. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Italy
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Ponatinib in cHronic myelOid LEukemia patieNts In Chronic phaSe: the PHOENICS Protocol
Overview
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.
Interventions
- 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
Primary outcome measures
- Ponatinib plasma concentrations [Time frame: 2 year]
Secondary outcome measures (2)
- Molecular response [Time frame: Up to 2 year]
- Occurrence of adverse events/adverse drug reactions [Time frame: Up to 2 year]
Eligibility criteria
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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
Italy · 5 centers
- University of Cagliari - Businco Hospital - Unit of Hematology and Bone Marrow Transplant — Cagliari
- Policlinico Milano — Milan
- University of Naples Federico II - Unit of Hematology — Naples
- Santa Chiara University Hospital — Pisa
- Ospedale S. Eugenio ASL 2 Roma — Roma
Publications
- 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. PMID 38543276
Identifiers
NCT: NCT06119269 · 23707