Detection of Cardiac Fibrosis in Patients With Lymphoma

Lymphoma Clinical Trial

Official title:

Non-invasive Detection of Cardiac Fibrosis After Administration of Doxorubicin-Based Chemotherapy in Patients With Lymphoma Using Cardiac Magnetic Resonance: A Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02055040
• Other study ID #: 11-443
• Status: Recruiting
• Phase: Phase 0
• First received: February 3, 2014
• Last updated: February 3, 2014
• Start date: March 2012

Study information

• Verified date: February 2014
• Source: Dana-Farber Cancer Institute
• Contact: Michael Jerosch-Herold, PhD
• Phone: 6175258959
• Email: mjerosch-herold[@]partners.org
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

This research study is a clinical trial. Clinical trials test the effectiveness of an investigational imaging technique to learn whether the investigational imaging technique works in detecting cardiac injury after the administration of certain chemotherapies, such as doxorubicin. "Investigational" means that the imaging technique is still being studied and that research doctors are trying to find out more about it-such as whether the technique can detect lower levels of cardiac injury after treatment with doxorubicin. It also means that the FDA has not yet approved the use of gadolinium or approved the use of CMR studies for detection of cardiac toxicity after doxorubicin.

The chemotherapy drug that you have been scheduled to be treated with, doxorubicin, has been associated with the development of heart failure in some patients.

Cardiac Magnetic Resonance (CMR) is a type of MRI scan that uses a magnetic field to produce pictures of the heart. The CMR scan has been used in other studies and information from those other research studies suggest that this imaging technique may help to better detect differences in the structure of the heart muscle after treatment with doxorubicin.

In this research study, the investigators hope that they can better detect changes in the heart muscle before and after treatment with doxorubicin with the CMR scan in hopes that cardiac injury can be detected and treated earlier to prevent heart failure.

Description:

If you decide to participate in this research study, you will be asked to undergo some screening procedures to determine if you are eligible. These procedures include: medical history, determination of kidney function and a pregnancy test (if applicable). The investigators will also ask you to sign a CMR safety screening form that makes sure it is safe for you to have the CMR scan. If you have metallic implants (pacemakers, defibrillators, or aneurysm clips) or metallic fragments in your eye, you should not have a CMR. If these tests show that you are eligible to participate in the research study, you will begin the study. If you do not meet the eligibility criteria, you will not be able to participate in this research study.

Visit 1 will take place prior to starting doxorubicin chemotherapy. The visit will take about 1.5 hours. The investigators will ask you to come to the Shapiro Cardiovascular Center at the Brigham and Women's Hospital for your study visit. For subjects that qualify, the investigators will bring you to the basement level of the hospital for the heart CMR scan, an echocardiogram and some blood work. Before your CMR scan the investigators will take some blood via the IV cannula. The investigators will take about 4 tubes of blood. This is equivalent to 2.5 tablespoons of blood. From this blood the investigators will test for blood markers of cardiac injury and compare these results to your other tests.

For the CMR scan, you will be asked to lie still on the scanner table that slides into a tunnel-shaped machine. Four electrocardiogram (EKG) patches with wires attached will be placed on your chest or your back to check your heart rate. The investigators will place an intravenous (IV) catheter in one of your arms. An IV catheter is a thin plastic tube that is put into a vein with a needle. The IV catheter will be used to give you a CMR contrast dye (gadolinium). The dye will help us to identify subtle changes within the heart muscle. This dye, gadolinium, is used routinely in CMR studies. The investigators will also draw a sample of blood from the IV catheter to measure your red blood cell count. Then, the scanner table will move slowly into the tunnel-shaped CMR machine so the pictures can be taken. The machine is slightly wider than your body and there may be little room to move. If you feel any discomfort or need to stop the test, you will be able to tell this to the research staff. You will be able to speak to them while you are having the CMR and they will be able to speak to you. If you think that you might be too anxious about being inside the narrow CMR scanner for a long period of time, the investigators may prescribe a drug to help you relax you if you think it might be helpful. The CMR scan will take one hour.

An echocardiogram is a test used by doctors to monitor heart function. An echocardiogram is a safe test that uses ultrasound to image the heart. After completion of the CMR test, you will have an echocardiogram. This test will take place in the same area as the CMR test. The echocardiogram test will take 40 minutes.

Visit 2 will take place about 2-4 weeks after your last cycle of doxorubicin chemotherapy. When you come back for Visit 2, you will have the same type of CMR scan, echocardiogram and blood testing that you had during Visit 1.

At Visit 3 the investigators will perform an exercise test on a bicycle. The test is designed to test the oxygen consumption of your body when exercising. It provides a way of quantifying the ability of the body to exercise. This test will take 30 minutes. During this test subjects sit on the bicycle for at least 3 minutes pedaling at a rate of 60 cycles per minute and slowly the work-load is increased until peak exercise is obtained. The investigators define peak exercise as being tired or breathless. Heart rate and blood pressure are recorded during the test. During the test you will breathe through a mouthpiece from which the investigators will measure oxygen levels.

It will take you 12-16 months to complete this research study, depending on the date and timing of your chemotherapy. During this time, the investigators will ask you to make 3 study visits. The investigators will call you after approximately six months to see how you are doing.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 77
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• New diagnosis of lymphoma

• Scheduled to undergo doxorubicin-based chemotherapy

Exclusion Criteria:

• Concurrent radiotherapy prior to the performance of both CMR studies

• Prior malignancy treated with chemotherapy or mediastinal radiotherapy

• Contraindications to performance of a magnetic resonance study: presence of implanted metallic object, implanted neural stimulator, ferromagnetic implants not deemed MRI safe, intra-ocular metallic foreign bodies, severe claustrophobia, pregnancy, inability to perform exercise test

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Lymphoma

Intervention

Procedure:
• Cardiac Magnetic Resonance Scan

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Early detection of DOX-induced cardiac injury	A novel cardiac magnetic resonance-based index of interstitial myocardial fibrosis. Dimensionless measure of extra-cellular volume fraction in myocardial tissue.	2 years	No
Secondary	Alteration of serum biomarkers after doxorubicin based chemotherapy	Serum biomarkers of cardiac stress, collagen turn-over, and myocardial injury. Values represent absolute serum concentrations.	2 years	No
Secondary	Alteration of echocardiographic indices after doxorubicin-based chemotherapy	Conventional and novel echocardiographic indices of cardiac function. Indices are dimensionless and represent ratios measured by echocardiography.	2 years	No
Secondary	Measurement of cardiopulmonary functional capacity	Measures of cardiopulmonary functional capacity.	2 years	No
Secondary	Determine association between measurements pre- and post-doxorubicin-based chemotherapy	Statistical measures of association between CMR, echocardiographic, serum and functional measures pre- and post-doxorubicin-based chemotherapy. Measures are unitless.	2 years	No