LEONIDAS: Quality of Life Study in Chronic Myeloid Leukemia Patients

Study Overview
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Brief Summary
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The broad goal of this study is to investigate if differences exist (and in which areas and of what magnitude) in QoL and symptoms of patients with CML being treated with first line therapy with dasatinib versus those receiving first line therapy with imatinib. Also, an additional objective is to characterize medication-taking behavior associated with imatinib or dasatinib.

Detailed Description
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The development of molecular targeted therapies (i.e., oral tyrosine kinase inhibitors [TKIs]) to treat chronic myeloid leukemia (CML) is one of the great triumphs of modern oncology and one of the spearheads of personalized medicine. Since their introduction in 2001, the number of people living with CML has doubled, a trend that is expected to continue. This study (i.e., LEONIDAS) is set up to generate evidence-based data and produce information that will advance scientific knowledge, clinical practice and health services management to facilitate clinical decision-making in CML. In an effort to further promote patient-centered care for CML a patient advocacy organization, that is the: CML Advocates Network, is involved in this project with key representatives who will be in the advisory board team. The CML Advocates Network, hosted by the patient-run, non-profit Leukemia Patient Advocates Foundation is a worldwide network of 82 non-profit organizations from 63 countries supporting patients with CML and their relatives. Rationale and Significance Some ten years ago, the treatment of CML was relatively straightforward as all patients received imatinib as first-line treatment and for those who failed imatinib, the only available proven alternative was allogeneic stem cell transplantation. Nowadays, with three effective drugs (i.e., imatinib, nilotinib and dasatinib), that can be used frontline in newly diagnosed chronic phase (CP) CML patients, treatment decision-making for individual patients in daily clinical practice has thus rapidly grown in complexity. Moreover, a new tyrosine kinase inhibitors (TKI), bosutinib, has been recently approved for as second-line treatment and undergoing clinical trials are assessing its efficacy as frontline strategy in CML. To further complicate the scenario, is the fact that despite nilotinib and dasatinib have been shown to have higher rates of cytogenetic and molecular responses (compared to imatinib), none of these three drugs is dramatically better than the others. To illustrate, only slightly differences exist in terms of progression-free survival for nilotinib and no differences for overall survival at 24 and/or 36 months amongst imatinib, dasatinib and nilotinib. Nevertheless, physician-reported toxicity data suggests these drugs have different toxicity profiles, with imatinib inducing a higher proportion of low-grade side effects than second generation tyrosine kinase inhibitors (TKI) (i.e. nilotinib and dasatinib). While a wealth of biomedical and laboratory data exists on clinical efficacy of these three drugs, the impact of these from the patients' perspective, in terms of Quality of Life (QoL) and symptom burden, has been poorly investigated. No data exists on QoL of patients treated with nilotinib or dasatinib and it is not known if these drugs provide better QoL outcomes over imatinib when used as first line therapy. Such information would be critical in the current CML arena to make more informed treatment decisions. This is a significant gap in our knowledge with respect to the modern management of CML, also because, as long-term continuous exposure to the tyrosine kinase inhibitors (TKI) is necessary, even low grade side effects can heavily impact on patients' QoL. Thus, the objective of this study is to investigate if differences exist (and in which areas and of what magnitude) in QoL and symptoms of patients with CML being treated with first line therapy with dasatinib versus those receiving first line therapy with imatinib, as well as characterizing medication-taking behavior associated with imatinib or dasatinib.

Official Title
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Mid to Long-term Quality of Life Effects Of imatiNIb Versus DASatinib in Chronic Myeloid Leukemia Patients (LEONIDAS)

Conditions
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Chronic Myeloid Leukemia

Intervention / Treatment
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* Other: QoL Survey Booklet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older at the time of study entry; Diagnosis of Philadelphia chromosome positive and/or BCR-ABL positive CML confirmed by cytogenetic and/or molecular analysis; At least in CCyR (as documented by chromosome banding analysis of marrow cell metaphases) or in MMR (≤0.1% BCR-ABL IS) CP-CML Patients in first line treatment with either dasatinib or imatinib for no more than 3 years; Written informed consent. Exclusion Criteria: Major cognitive deficits or psychiatric problems hampering a self-reported evaluation. Not speaking and reading the language of the participating country. Having received any CML treatment prior to therapy with imatinib or dasatinib for more than three months.

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Imatinib<br>Patients in first line treatment with imatinib for no more than 3 years. | Other: QoL Survey Booklet<br> <br> |
| Dasatinib<br>Patients in first line treatment with dasatinib for no more than 3 years. | Other: QoL Survey Booklet<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of the impact of therapy on daily life in patients with CP-CML being treated with first line therapy with dasatinib and those receiving first line therapy with imatinib. | (outcome measure: European Organization for Research and EORTC QLQ-CML24 Impact on daily life scale) | 24 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in Patient-reported outcomes between imatinib- and dasatinib- treated CP- CML patients in the following QoL domains: Fatigue, Physical, Social and Role Functioning and Impact on worry and mood and Symptom burden. | (outcome measure: EORTC QLQ-C30 and EORTC QLQ-CML24) | 24 months. | 
| Proportion of patients considered as low, medium and high adheres by type of therapy. | (outcome measure: Morisky-Medication Adherence Scale-MMAS) | 24 months. | 
| Relationship between patient's perception of disease-/treatment-related information received , QoL profile and adherence to therapy. | (defined according to the EORTC-QLQ-INFO25) | 24 months. | 
| Degree of agreement in the assessment of symptom severity, for a set of core CML treatment related symptoms , between patients and their treating physicians. | (according to the EORTC-QLQ-CML24) | 24 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Quality of Life, Chronic Myeloid Leukemia, Imatinib, Dasatinib