Vascular Cardiotoxicity of Ponatinib

Cardiotoxicity Clinical Trial

Official title:

Vascular Cardiotoxicity of Ponatinib

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03930394
• Other study ID #: Ponatinib Cardiotoxicity
• Status: Recruiting
• Start date: May 15, 2019
• Est. completion date: May 1, 2022

Study information

• Verified date: June 2019
• Source: Oregon Health and Science University
• Contact: Melinda Wu, MD
• Phone: 503 494-4772
• Email: wume[@]ohsu.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Pre-clinical studies suggest that the third generation tyrosine kinase inhibitor ponatinib can result in microvascular angiopathy and acceleration of atherosclerosis. This study is intended to examine for myocardial microvascular angiopathy and changes in carotid plaque in patients receiving ponatinib as part of their clinical care.

Description:

In this study, we will perform serial echocardiography for ventricular function, myocardial contrast echocardiography for microvascular perfusion assessment, blood analysis for myocardial injury, and carotid US for plaque or IMT progression in subjects receiving ponatinib. This series of tests is intended to provide information on the presence of clinically-evident or subclinical microvascular angiopathy and plaque acceleration.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: May 1, 2022
• Est. primary completion date: May 1, 2021
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

• Diagnosis of CML or ALL

• Prescribed ponatinib

Exclusion Criteria:

• pregnancy or lactation

• major medical illness involving the heart or vasculature (CAD, PAD, DCM).

• hemodynamically unstable

• allergy to ultrasound contrast agents.

Related Conditions & MeSH terms

• Cardiotoxicity

Intervention

Diagnostic Test:
• Contrast ultrasound perfusion imaging
Contrast ultrasound perfusion imaging for microvascular perfusion, and carotid ultrasound data on intima-media thickness (or plaque size) will be serially assessed in subjects started on ponatinib.

Locations

Country	Name	City	State
United States	Oregon HSU	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Oregon Health and Science University

Country where clinical trial is conducted

United States, 

References & Publications (1)

Latifi Y, Moccetti F, Wu M, Xie A, Packwood W, Qi Y, Ozawa K, Shentu W, Brown E, Shirai T, McCarty OJ, Ruggeri Z, Moslehi J, Chen J, Druker BJ, López JA, Lindner JR. Thrombotic microangiopathy as a cause of cardiovascular toxicity from the BCR-ABL1 tyrosine kinase inhibitor ponatinib. Blood. 2019 Apr 4;133(14):1597-1606. doi: 10.1182/blood-2018-10-881557. Epub 2019 Jan 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Presence versus absence of any myocardial perfusion defect assessed by visual analysis for any abnormalities of microvascular flux rate (beta function) or microvascular blood volume during an infusion of ultrasound microbubble contrast agents.	Contrast ultrasound perfusion imaging will be performed using power-modulation imaging and infusion of an ultrasound contrast agent. Destruction replenishment kinetics will be assessed visually by examination of delayed replenishment of signal intensity (>5 seconds) after a high-mechanical index burst sequence, or abnormalities in plateau intensity reflecting regional abnormalities in myocardial microvascular blood volume.	6 months
Primary	Presence versus absence of any myocardial perfusion defect assessed by visual analysis for any abnormalities of microvascular flux rate (beta function) or microvascular blood volume during an infusion of ultrasound microbubble contrast agents.	Contrast ultrasound perfusion imaging will be performed using power-modulation imaging and infusion of an ultrasound contrast agent. Destruction replenishment kinetics will be assessed visually by examination of delayed replenishment of signal intensity (>5 seconds) after a high-mechanical index burst sequence, or abnormalities in plateau intensity reflecting regional abnormalities in myocardial microvascular blood volume.	12 months
Primary	Carotid plaque size	Changes in IMT or plaque size	6 months
Primary	Carotid plaque size	Changes in IMT or plaque size	12 months