The EMPATHY Pilot Study

Study Overview
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Brief Summary
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The proposed study, may significantly contribute to improve healthcare delivery in patients with Chronic Myeloid Leukemia (CML) treated with modern tyrosine kinase inhibitors (TKIs) in two ways. First, it may provide novel empirical data on the positive effects of systematically monitoring of patient-reported adverse events (AEs) in routine practice for improving symptom management and adherence to therapy. Second, it will inform the development of a large international randomized controlled trial (RCT) to test whether systematic collection of patient-reported AEs, could improve clinical response to TKI therapy.

Detailed Description
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The evolution in the understanding of the biology of Chronic Myeloid Leukemia (CML), that eventually translated into highly effective molecular targeted therapies, is unparalleled in cancer medicine. This knowledge led the development of a number of orally active molecule tyrosine kinase inhibitors (TKIs) that have dramatically improved clinical outcomes. In less than two decades, the 10-year survival probability increased from 20 to 53% with previous (IFN)-therapies to about 90% in the TKI era. Life expectancy of these patients now approaches that of the general population. While oral TKIs are now the standard of care for CML, it should be considered that therapy is lifelong and patients are requested to take medication on a daily basis. Importantly, there is convincing evidence that full adherence to therapy is a critical factor to obtain and maintain an optimal response to therapy. However, non-adherence is a major challenge in CML, since side effects induced by these drugs negatively impact on patient's quality of life (QoL), seriously undermine full adherence with treatment schedule and thereby often lead to sub-optimal clinical responses to drugs. From previous Preliminary Data we extrapolated the following evidences: Systematic monitoring of Patient-Reported Outcomes (PRO) in routine care has several advantages, such as improved symptom control, enhanced patient-physician communication, as well as patient satisfaction and wellbeing. Furthermore, it was found that Adverse Events (AEs) are the most frequent cause for non-adherence to CML therapy and that even experienced physicians tend to underestimate burden of TKIs of their patients. This mismatch might have major clinical implications in disease management, as physicians might not be able to early identify those patients who might be at heightened risk of poor adherence behavior. Given these findings, we hypothesized that systematic electronic monitoring of Patient-Reported AEs in CML routine practice may improve adherence to therapy, quality of life, and clinical response to therapy. This hypothesis will be addressed in the experiments of the following Specific Aims: 1) To develop an online platform for systematic monitoring of patient-reported AE assessment that is tailored to the unique demands of TKI therapy for CML. 2) To assess patient and physician acceptability and satisfaction with use of this platform in CML routine practice and evaluate its value in improving symptom management, quality of life, adherence to therapy as well as preliminary efficacy. We anticipate this study will provide unprecedented information on the value of systematically collecting patient-reported AEs information in CML routine care. If positive, our results will inform the development of large international randomized controlled trial (RCT) to investigate whether this experimental approach can improve depth and rates of clinical responses to TKI therapies in CML patients. Dr. Fabio Efficace is also a Principal Investigator on this study. He is also a Professor in the Department of Medical Social Sciences at Northwestern University, Feinberg School of Medicine.

Official Title
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Evaluating Patient-Reported Outcomes Monitoring in Routine Care of Patients With Chronic Myeloid Leukemia for Increasing Adherence and Clinical Response to THerapY: The EMPATHY Pilot Study

Conditions
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Cancer, Leukemia, Chronic Myeloid

Intervention / Treatment
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* Other: EMPATHY Pilot


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Philadelphia chromosome positive and/or BCR-ABL positive CML confirmed by cytogenetic and/or molecular analysis; Newly diagnosed chronic phase (CP)-CML Patients planned to receive one of the following TKI approved as first line treatment: imatinib, dasatinib, nilotinib or bosutinib; Adult Patients (≥18 years) at the time of study entry; Children under the age of 18 will be excluded from the study. The exclusion of children is justified by the following circumstances: a) The condition is relatively rare in children, as compared to adults; b) Issues of study preclude direct applicability of hypotheses and/or interventions to both adults and children. Written informed consent. Written informed consent from Patient's physician as a participant. Newly diagnosed Chronic Phase (CP)-CML Patients who are within 4 weeks of first line TKI therapy (anyone of the TKI approved in the USA and Europe, that is: imatinib, dasatinib, nilotinib or bosutinib). Ability to read/converse in English (Northwestern University and Augusta University Sites). Ability to read/converse in Italian (GIMEMA Centers). Patient exclusion criteria will include: Major cognitive deficits or psychiatric problems hampering a self-reported evaluation; Having received any CML treatment - other than TKI - for more than 3 months prior to receiving current TKI therapy. This project will focus on CML, which affect both men and women. Therefore, there are no exclusion/inclusion criteria based on sex/gender. In addition, there are no exclusion/inclusion criteria based on race and ethnicity. Physician inclusion criteria will include: 1)Provider of clinical care for Patient who meets inclusion criteria for the study Please note that Physician consent is requisite for the Patient to be enrolled as a participant in the study. Exclusion Criteria: Major cognitive deficits or psychiatric problems hampering a self-reported evaluation Having received any CML treatment prior to therapy with imatinib, dasatinib, bosutinib or nilotinib 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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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chronic myeloid leukemia (CML) patients<br>CML patients undergoing first-line tyrosine kinase inhibitor (TKI) therapy | Other: EMPATHY Pilot<br>* The goal of this pilot is to develop and pilot a tailored monitoring intervention targeting symptomatic, Patient-reported adverse events (AEs) in chronic myeloid leukemia (CML) Patients undergoing first-line tyrosine kinase inhibitor (TKI) therapy. The tailored monitoring intervention will draw primarily from the PRO-CTCAE Item Library, with additional items drawn from the FACIT and EORTC Item libraries as necessary. After identifying the full set of AEs to be monitored, we will load the Patient assessment and report program into tablets for electronic administration in the busy clinic setting. We will then pilot a six-month intervention aimed to monitor and manage emerging AEs, coupled with assessment of intervention feasibility, Patient acceptability and satisfaction, provider acceptability and clinical management utility, adherence to TKI therapy, and HRQoL. We expect that adherence to therapy, clinical response, and HRQoL will be enhanced by such an intervention.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Medication Adherence | Adherence to Refills and Medications Scale | 6 months | 
| Medication Adherence | Prescription refill data extracted from hospital pharmacy records. Prescription refill data will be evaluated over 6 months. Missed refills, for reasons other than mortality or physician change of medication, will count as non-adherence | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Health-Related Quality of Life | Functional Assessment of Cancer Therapy-General | 6 months | 
| Fatigue | Functional Assessment of Chronic Illness Therapy-Fatigue | 6 months | 
| Patient Satisfaction | Patient satisfaction with the study platform. Author-constructed items include questions on overall satisfaction and acceptability with the study website. | 6 months | 
| Cytogenetic response | Cytogenetic response (CyR) is defined based on the percentage of Ph pos metaphases, as evaluated by chromosome banding analysis of at least 20 marrow cell metaphases (cytogenetics). Complete CyR is when the percentage of Ph pos metaphases is 0; Partial CyR is when the percentage of Ph pos metaphases ranges from 1 to 35, Minor CyR if the percentage of Ph pos metaphases ranges from 36 to 65, minimal CyR if the percentage of Ph pos metaphases ranges from 66 to 95, No CyR if the percentage of Ph pos metaphases is higher than 95. | 6 months | 
| Physician acceptability | physician acceptability of study platform. Author-constructed questionnaire includes items assessing physician satisfaction and acceptability of the study website. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Leukemia, Chronic Myeloid, Health-Related Quality Of Life, Patient Reported Outcome