Trial Title:
Ponatinib in CML Patients in Chronic Phase
NCT ID:
NCT06119269
Condition:
Chronic Myeloid Leukemia, Chronic Phase
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Conditions: Keywords:
Chronic myeloid leukemia, chronic phase
Ponatinib
Therapeutic drug monitoring
Efficacy
Tolerability
Study type:
Observational
Overall status:
Recruiting
Study design:
Time perspective:
Retrospective
Intervention:
Intervention type:
Diagnostic Test
Intervention name:
Therapeutic drug monitoring
Description:
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)
Intervention type:
Diagnostic Test
Intervention name:
Molecular Response
Description:
BCR-ABl transcript levels will be assessed to evaluate molecular response to ponatinib
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.
Criteria for eligibility:
Study pop:
Patients diagnosed with CML-CP who received ponatinib as 2nd-4th chemotherapy line will
be enrolled according to inclusion/exclusion criteria listed.
Sampling method:
Non-Probability Sample
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Cagliari - Businco Hospital - Unit of Hematology and Bone Marrow Transplant
Address:
City:
Cagliari
Zip:
09124
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Giovanni Caocci, PhD
Phone:
+39 070 5296
Phone ext:
2065
Email:
giovanni.caocci@unica.it
Facility:
Name:
Policlinico Milano
Address:
City:
Milano
Zip:
20122
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Alessandra Iurlo, MD
Phone:
+39 02 5503.1
Phone ext:
3422
Email:
alessandra.iurlo@policlinico.mi.it
Facility:
Name:
University of Naples Federico II - Unit of Hematology
Address:
City:
Napoli
Zip:
80131
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Luigia Luciano, MD
Phone:
+39 081 746
Phone ext:
2165
Email:
lulucian@unina.it
Facility:
Name:
Santa Chiara University Hospital
Address:
City:
Pisa
Zip:
56126
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Sara Galimberti, PhD
Phone:
+39 050 993111
Phone ext:
3488
Email:
sara.galimberti@unipi.it
Contact backup:
Last name:
Claudia Baratè, MD
Phone:
+39 050 992111
Email:
claudia.barate@gmail.com
Investigator:
Last name:
Federica Ricci, MD
Email:
Sub-Investigator
Investigator:
Last name:
Marinunzia Franciosa, MD
Email:
Sub-Investigator
Investigator:
Last name:
Ignazio Santo, MD
Email:
Sub-Investigator
Investigator:
Last name:
Antonello Di Paolo, MD
Email:
Sub-Investigator
Investigator:
Last name:
Francesca Guerrini, BiolD
Email:
Sub-Investigator
Facility:
Name:
Ospedale S. Eugenio ASL 2 Roma
Address:
City:
Roma
Zip:
00144
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Elisabetta Abruzzese, MD
Phone:
+39 06 51001
Email:
elisabetta.abruzzese@uniroma2.it
Start date:
August 2, 2023
Completion date:
December 31, 2024
Lead sponsor:
Agency:
University of Pisa
Agency class:
Other
Source:
University of Pisa
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06119269
