Vascular Cardiotoxicity of Ponatinib

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.

Study Overview

• Status: Unknown
• Conditions: Cardiotoxicity
• Intervention / Treatment: Diagnostic test: Contrast ultrasound perfusion imaging

Detailed 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.

• Study Type: Observational
• Enrollment (Anticipated): 32

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97221
      • Recruiting
      • Oregon HSU
      • Contact: Melinda Wu, MD; Phone Number: 503-494-9000; Email: wume@ohsu.edu
      • Contact: Jonathan Lindner, MD; Phone Number: 503494900; Email: lindnerj@ohsu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Subjects diagnosed with CML or ALL who are to be treated with ponatinib.

Description

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.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Carotid plaque size	Changes in IMT or plaque size	6 months
Carotid plaque size	Changes in IMT or plaque size	12 months

Collaborators and Investigators

• Sponsor: Oregon Health and Science University

Publications and helpful links

General Publications

• 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, Lopez 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2019
• Primary Completion (Anticipated): May 1, 2021
• Study Completion (Anticipated): May 1, 2022

Study Registration Dates

• First Submitted: April 24, 2019
• First Submitted That Met QC Criteria: April 26, 2019
• First Posted (Actual): April 29, 2019

Study Record Updates

• Last Update Posted (Actual): June 7, 2019
• Last Update Submitted That Met QC Criteria: June 5, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Wounds and Injuries; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Cardiotoxicity
• Other Study ID Numbers: Ponatinib Cardiotoxicity

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No