Ivabradine in the Management of Cardiac Autonomic Dysfunction Associated With Thoracic Radiation Therapy.

This research study is a Phase II clinical trial. Phase II clinical trials test the safety
and effectiveness of an investigational intervention to learn whether the intervention works
in treating a specific disease. "Investigational" means that the intervention is being
studied.

This research study is a Pilot Study, which is the first time investigators are examining
this study intervention for this particular problem.

In this research study, the investigators are studying a drug called ivabradine. The
investigators are exploring whether ivabradine can be used to reduce heart rate, increase
exercise duration, and improve quality of life in survivors of lymphoma who received
radiation to their chest as a part of their cancer treatment.

The U.S. Food and Drug Administration (FDA) has not approved ivabradine for this specific
disease, but it has approved the drug as an oral medication to lower heart rate in heart
failure patients.

Survivors of lymphoma who were treated with neck and/or chest radiation can have an elevated
resting heart rate and an abnormal rate of decline in their heart rate after exercise, also
known as cardiac autonomic dysfunction. These abnormalities can limit exercise duration and
worsen quality of life in some radiation treated survivors of lymphoma

Inclusion Criteria:

- Survivors of mediastinal lymphoma (either Non-Hodgkin's Lymphoma or Hodgkin's
Lymphoma) with no active malignancy

- Prior mediastinal or mantle radiation ≥ 5 years prior to enrollment in the study

- Age 18-80 years.

- Participants must have normal organ function as defined below:

- AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal

- creatinine clearance ≥ 15 mL/min/1.73 m2 for participants with creatinine levels
above institutional normal.

- Normal sinus rhythm with resting heart rate ≥ 80 bpm on screening EKG

- Based on findings in animals, ivabradine may cause fetal harm when administered to a
pregnant woman. For this reason, women of child-bearing potential must agree to use
adequate contraception.

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Participants who are receiving any other investigational agents.

- History of allergic reaction to ivabradine.

- Participants receiving any medications or substances that are inhibitors or inducers
of cytochrome P450 3A4 are ineligible.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, acute coronary syndrome, symptomatic
known coronary artery disease, severe valvular heart disease, active malignancy, or
psychiatric illness/social situations that would limit compliance with study
requirements.

- Pregnant women are excluded from this study because ivabradine is an agent with the
potential for teratogenic effects. Because there is an unknown but potential risk for
adverse events in nursing infants secondary to treatment of the mother with
ivabradine, breastfeeding should be discontinued if the mother is treated with
ivabradine.

- HIV-positive participants on combination antiretroviral therapy.

- Patients with systolic blood pressure < 90 mm Hg.

- Patients with sick-sinus syndrome, sino-atrial block, third degree heart block, atrial
fibrillation, and those with permanent pacemakers.

- Patients with other established indications for ivabradine: stable, symptomatic
chronic HF with a left ventricular ejection fraction ≤ 35% and in sinus rhythm with a
resting HR ≥ 70 bpm, who are taking maximally tolerated doses of beta-blockers or have
contraindications to beta-blocker use.

- Patients with severe hepatic dysfunction (Child Pugh Class C).

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier.