Ponatinib in CML Patients in Chronic Phase (PHOENICS)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Myeloid Leukemia, Chronic Phase
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Sara Galimberti, PhD; Phone Number: 3488 +39 050 993111; Email: sara.galimberti@unipi.it
• Study Contact Backup: Name: Claudia Baratè, MD; Phone Number: +39 050 992111; Email: claudia.barate@gmail.com

Study Locations

• Italy
  • Cagliari, Italy, 09124
    • Recruiting
    • University of Cagliari - Businco Hospital - Unit of Hematology and Bone Marrow Transplant
    • Contact: Giovanni Caocci, PhD; Phone Number: 2065 +39 070 5296; Email: giovanni.caocci@unica.it
  • Milano, Italy, 20122
    • Recruiting
    • Policlinico Milano
    • Contact: Alessandra Iurlo, MD; Phone Number: 3422 +39 02 5503.1; Email: alessandra.iurlo@policlinico.mi.it
  • Napoli, Italy, 80131
    • Recruiting
    • University of Naples Federico II - Unit of Hematology
    • Contact: Luigia Luciano, MD; Phone Number: 2165 +39 081 746; Email: lulucian@unina.it
  • Pisa, Italy, 56126
    • Recruiting
    • Santa Chiara University Hospital
    • Sub-Investigator: Antonello Di Paolo, MD
    • Contact: Sara Galimberti, PhD; Phone Number: 3488 +39 050 993111; Email: sara.galimberti@unipi.it
    • Contact: Claudia Baratè, MD; Phone Number: +39 050 992111; Email: claudia.barate@gmail.com
    • Sub-Investigator: Federica Ricci, MD
    • Sub-Investigator: Marinunzia Franciosa, MD
    • Sub-Investigator: Ignazio Santo, MD
    • Sub-Investigator: Francesca Guerrini, BiolD
  • Roma, Italy, 00144
    • Recruiting
    • Ospedale S. Eugenio ASL 2 Roma
    • Contact: Elisabetta Abruzzese, MD; Phone Number: +39 06 51001; Email: elisabetta.abruzzese@uniroma2.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with CML-CP who received ponatinib as 2nd-4th chemotherapy line will be enrolled according to inclusion/exclusion criteria listed.

Description

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.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ponatinib plasma concentrations	Plasma concentrations of ponatinib included in the therapeutic range (i.e., >21 nM)	2 year

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Pisa
• Investigators: Principal Investigator: Sara Galimberti, PhD, University of Pisa - Dept. Clinical and Experimental Medicine

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2023
• Primary Completion (Estimated): January 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: October 18, 2023
• First Submitted That Met QC Criteria: November 3, 2023
• First Posted (Actual): November 7, 2023

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 3, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Efficacy; Therapeutic drug monitoring; Tolerability; Ponatinib; Chronic myeloid leukemia, chronic phase
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Chronic Disease; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Other Study ID Numbers: 23707

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No