Observational Study on CML Patients in Any Phase of the Disease Treated With Ponatinib (Iclusig®)

Study Overview
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Brief Summary
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This is a multicentre ambispective cohort study involving French patients who have started or are receiving for less than 6 months a treatment with ponatinib. This study aims at better qualifying the ponatinib benefit-risk balance in real life and in relation with CML patients' therapeutic history.

Official Title
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Observational Study on CML Patients in Any Phase of the Disease Treated With Ponatinib (Iclusig®): A Multicentre, Ambispective Cohort Study

Conditions
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Chronic Myeloid Leukemia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Presenting a CML in any phase. Having initiated for less than six months a treatment with ponatinib. The ability to understand the requirements of the study and to comply with the study data collection procedures. Exclusion Criteria: Patients previously treated with investigational ponatinib (within a clinical trial). Patients receiving an investigational agent. Patients who are pregnant and/or breastfeeding. Patients with contraindications for Ponatinib according to Summary of Products Characteristics.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| For participants in chronic myeloid leukemia in chronic (CP-CML) phase: Proportion of participants who achieve a major molecular response after the initiation of study treatment | Chronic myeloid leukemia (CML) response criteria as defined by the European LeukemiaNet Recommendations for Management of Chronic Myeloid Leukemia (Hochhaus et al Leukemia 2020). | from 24-60 months | 
| For participants in chronic myeloid leukemia in accelerated phase (AP-CML) or chronic myeloid leukemia in blast phase (BP-CML): Proportion of participants who achieve a complete hematologic response | CML response criteria as defined by the European LeukemiaNet Recommendations for Management of Chronic Myeloid Leukemia. | from 24-60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants in CP-CML phase who achieved complete hematologic response | CML response criteria as defined by the European LeukemiaNet Recommendations for Management of Chronic Myeloid Leukemia. | from 24-60 months | 
| Proportion of participants in AP and BP phases who achieved major (complete + partial) cytogenetic response | CML response criteria as defined by the European LeukemiaNet Recommendations for Management of Chronic Myeloid Leukemia. | from 24-60 months | 
| Proportion of participants who achieved major molecular response and/or depth molecular response: (MR4 or MR4.5 or MR5) | CML response criteria as defined by the European LeukemiaNet Recommendations for Management of Chronic Myeloid Leukemia. | from 24-60 months | 
| Duration of response | Duration of CML response criteria as defined by the European LeukemiaNet Recommendations for Management of Chronic Myeloid Leukemia. | from 24-60 months | 
| Time to progression to AP-CML or BP-CML (for those participants not in AP-CML or BP-CML) | Time to progression to AP-CML defined as follows: Blasts in blood or marrow 15%-29%, or blasts plus promyelocytes in blood or marrow > 30%, with blasts < 30%; basophils in blood ≥ 20%; persistent thrombocytopenia (< 100 × 10^9/L) unrelated to therapy; clonal chromosome abnormalities in Ph1 cells (CCA/Ph1), major route, on treatment. Time to progression to BP-CML defined as follows: Blasts in blood or marrow ≥ 30%; extramedullary blast proliferation, apart from spleen. | from 24-60 months | 
| Dose reduction (after response) in each cohort | Includes level of response at the time of dose reduction and maintenance of response after dose reduction. | from 24-60 months | 
| Time to response | Time to CML response criteria as defined by the European LeukemiaNet Recommendations for Management of Chronic Myeloid Leukemia. | from 24-60 months | 
| Rate of progression to accelerated phase (AP-) or blast phase (BP-) CML | Rate of progression to AP- or BP-CML as defined in European LeukemiaNet (ELN) criteria. | from 24-60 months | 
| Progression-free survival (PFS) | Survival without any progression to AP or BP according to ELN criteria. | from 24-60 months | 
| Overall survival (OS) | Overall survival defined according to ELN criteria. | from 24-60 months | 
| Rate of adverse events | Adverse event is any untoward medical occurrence in a patient or clinical study subject administered a medicinal (investigational or non-investigational) product. An adverse event does not necessarily have a causal relationship with the treatment. | from 24-60 months | 
| Rate of discontinuation due to adverse events in each dose cohort | Adverse event is any untoward medical occurrence in a patient or clinical study subject administered a medicinal (investigational or non-investigational) product. An adverse event does not necessarily have a causal relationship with the treatment. | from 24-60 months | 
| Dose reductions (prior to response) in each dose cohort | Reduction in the dose of Iclusig. | from 24-60 months | 
| Dose interruptions in each dose cohort | Interruption of Iclusig treatment. | from 24-60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic myeloid leukemia, Iclusig, ponatinib