Determining Change in Cardiovascular and Metabolic Risks in Patients With Chronic Phase Chronic Myeloid Leukemia Receiving BCR-ABL Tyrosine Kinase Inhibitor First-Line Therapy in the United States

Study Overview
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Brief Summary
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This non-interventional, prospective study will characterize the impact of three approved first and second generation BCR-ABL1 tyrosine kinase inhibitors on cardiovascular and metabolic risk factors in chronic phase CML (CP-CML) patients who are TKI naive and initiating first-line TKIs in routine clinical practice in the US. All treatment decisions will be determined at the discretion of the treating physician(s) and data identifying the cardiovascular and metabolic risk factors will be collected. Additional fasting blood samples (collected following 8 hours of fasting) will be collected during standard of care (SOC)/routine office visits. Additional research imaging will be performed and will be reviewed by core imaging laboratory. As the study is collecting data on management of CML, this study will not influence the prescribing or management practices at participating sites.

Detailed Description
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This non-interventional, prospective study will characterize the impact of three approved first and second generation BCR-ABL1 tyrosine kinase inhibitors on cardiovascular and metabolic risk factors in chronic phase CML (CP-CML) patients who are TKI naive and initiating first-line TKIs in routine clinical practice in the US. All treatment decisions will be determined at the discretion of the treating physician(s) and data identifying the cardiovascular and metabolic risk factors will be collected. Additional fasting blood samples (collected following 8 hours of fasting) will be collected during standard of care (SOC)/routine office visits. Additional research imaging will be performed and will be reviewed by core imaging laboratory. As the study is collecting data on management of CML, this study will not influence the prescribing or management practices at participating sites.

Official Title
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Determining Change in Cardiovascular and Metabolic Risks in Patients With Chronic Phase Chronic Myeloid Leukemia Receiving BCR-ABL Tyrosine Kinase Inhibitor First-Line Therapy in the United States

Conditions
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Chronic Phase Chronic Myeloid Leukemia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years at the time of Ph+ CP-CML diagnosis Newly diagnosed chronic phase of Ph+ CP-CML, confirmed with cytogenetic and/or molecular testing at baseline Treatment-naïve and initiating treatment with dasatinib, imatinib, nilotinib or bosutinib Willingness and ability to comply with routine office visits Exclusion Criteria: Any other prior or active non-CML active malignancy for which the patient is receiving treatment Participation in a therapeutic clinical trial for CML disease

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 |
| --- | --- |
| dasatinib cohort<br>Intended to characterize the impact of dasatinib on cardiovascular and metabolic risk factors in CP-CML treated patients who are TKI naive and initiating first line TKIs in routine clinical practice in the US. | |
| imatinib cohort<br>Intended to characterize the impact of imatinib on cardiovascular and metabolic risk factors in CP-CML treated patients who are TKI naive and initiating first line TKIs in routine clinical practice in the US. | |
| nilotinib cohort<br>Intended to characterize the impact of nilotinib on cardiovascular and metabolic risk factors in CP-CML treated patients who are TKI naive and initiating first line TKIs in routine clinical practice in the US. | |
| bosutinib cohort<br>Intended to characterize the impact of bosutinib on cardiovascular and metabolic risk factors in CP-CML treated patients who are TKI naive and initiating first line TKIs in routine clinical practice in the US. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in cardiovascular risk from baseline using the Framingham Coronary Heart Disease Score |  | up to 24 months | 
| changes in metabolic risk from baseline using metabolic lab values |  | up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| echocardiography to assess left ventricular function |  | up to 24 months | 
| urinary protein excretion to assess early vascular endothelial changes |  | up to 24 months | 
| coronary calcium scoring to assess coronary artery narrowing |  | up to 24 months | 
| metabolic labs (Plasma Glucose, HbA1c, Fasting Lipids) for assessing the metabolic disease |  | up to 24 months | 
| safety and tolerability of first-line BCR-ABL TKIs in adults with CP-CML based on the number of treatment-related adverse events collected in the medical records |  | up to 24 months | 
| clinical outcomes as described by the number of deaths from clinical assessments of disease status and mutational analysis |  | up to 24 months | 
| clinical outcomes as described by the major molecular response from clinical assessments of disease status and mutational analysis |  | up to 24 months | 
| clinical outcomes as described by the cytogenetic response from clinical assessments of disease status and mutational analysis |  | up to 24 months | 
| time to development of clinical outcomes from baseline to time of clinical outcome event based on clinical assessments |  | up to 24 months | 
| description of treatment patterns based on the number of changes in treatment dosing, interruptions, changes in therapy, duration of therapy and treatment discontinuations through the management of adverse events and comorbid disease |  | up to 24 months | 
| description of the demographic and clinical patient characteristics associated with initial treatment choice and changes of treatment based on the medical records |  | up to 24 months | 
| measurement of serum biomarkers that are predictive of an increased risk for cardiovascular or metabolic disease |  | up to 24 months |