Cardioprotection in AML
Phase II Trial of Cardioprotective Prophylaxis With Combination of Beta Blocker and Angiotensin-Converting Enzyme Inhibitors During Intensive Chemotherapy for Patients With Newly Diagnosed Acute Myeloid Leukemia
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years and older
- Sex
- All sexes
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
- Procedures mentioned: Heart tracing (ECG), Blood draws, Questionnaires
Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.
Show the study's own words
- "Everyone will have electrocardiograms (also called ECGs or EKGs) and echocardiograms before and at multiple timepoints during the study."
- "They will also have a special blood test to see their levels of troponin, a protein that helps with muscle contractions in your heart."
- "All participants will complete questionnaires at a few timepoints during the study to measure their quality of life."
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This study tests whether two heart medicines, a beta blocker and an ACE inhibitor, can prevent heart damage from AML cancer treatment. It is for adults with newly diagnosed acute myeloid leukemia (AML), a blood cancer. Participants are assigned by chance to take these heart medicines or not take them.
Patients with acute myeloid leukemia (AML) often receive a drug called daunorubicin. Daunorubicin is a type of drug called an anthracycline, which increases the risk of some damage to the heart. Beta blockers and angiotensin-converting enzyme inhibitors (ACEi) are two types of drugs that are often used (and are FDA approved) to treat the type of damage to the heart caused by anthracyclines. They have also been used in some populations to prevent this type of heart damage. In this study, participants will be randomly assigned to either preventively take a beta blocker and ACEi or not to receive these. The primary purpose of the study is to look at how often people in each group develop this type of heart damage. The study investigators will also collect data about your quality of life and other changes in your heart function. Frequency and severity of anthracycline-induced cardiotoxicity among patients receiving acute myeloid leukemia (AML) chemotherapy is unknown. We hypothesize that up-titrating study agents to maximum tolerated dosage at the time of induction (starting treatment for AML) will prevent the development of systolic dysfunction as determined on serial echocardiography.
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- You are 18 or older and have newly diagnosed AML.
- You sign a consent form before study screening, understand the study, and can follow its treatment and follow-up steps.
- You can care for yourself and are out of bed or a chair for at least half of your waking hours (ECOG score of 0–2).
- You plan to start AML treatment with an anthracycline, a type of cancer drug. You may have started other parts of treatment, but not the anthracycline.
- Your liver and kidney tests meet study limits: bilirubin no more than 1.5 times normal, or less than 3 times normal with Gilbert's syndrome; AST and ALT liver tests no more than 2.5 times normal; and kidney clearance above 60 mL/min.
- You can swallow medicine and agree to follow the beta blocker and lisinopril treatment plan.
- Before starting AML treatment, a heart ultrasound shows your heart pumps out at least 50% of the blood in its main pumping chamber with each beat.
- Men and women who can become pregnant agree to avoid sex or use reliable birth control during chemotherapy or ACE inhibitor treatment, which can harm an unborn baby.
Who can't join
- You already take a beta blocker, ACE inhibitor, or ARB heart or blood pressure medicine, or you are allergic to beta blockers or ACE inhibitors.
- You have uncontrolled chest pain or heart rhythm problems, had a heart attack in the past 6 months, or have mental health or social problems that could keep you from following study steps.
- You take another study drug now or took one within the past week. An exception is allowed if its side effects are well known and it is not known to protect or harm the heart.
- You are pregnant or breastfeeding.
- You have a life-threatening illness other than AML, uncontrolled illness, or organ problems that could affect safety or study results; an active, untreated, or severe infection; or serious liver disease, including liver scarring, a past liver transplant, or liver-related kidney failure.
- You have had a blood stem cell transplant with active graft-versus-host disease, where donor cells attack your body, or have used immune-suppressing drugs other than low-dose prednisone (5 mg or less) or calcineurin inhibitors in the past 4 weeks.
- You have moderate or severe disease of the heart's mitral or aortic valve, current or past heart failure, or a heart defect present at birth that prevents more anthracycline treatment.
- At the start of AML treatment, your resting pulse is 60 beats per minute or lower, you have a complete block of electrical signals in your heart, or your top blood pressure number is below 95.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
Inclusion Criteria: 1. Signed informed consent obtained prior to conducting any study-specific screening procedures. 2. Willing and able to understand the nature of this study and to comply with both the study as well as follow-up procedures for the duration of the study. 3. Age ≥ 18 years old with newly-diagnosed Acute Myeloid Leukemia (AML) 4. ECOG performance status must be ≤ 2 5. Planning to receive initial induction therapy containing an anthracycline for AML. Participants may have started initial induction therapy if anthracycline has not yet been administered. 6. Adequate organ function as evidenced by the following laboratory findings: 1. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) or \< 3 x ULN for patients with Gilbert's Syndrome 2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN 3. Creatinine clearance \> 60 mL/min 7. Ability to take oral medication and a willingness to adhere to the beta blocker and lisinopril regimen 8. Echocardiogram demonstrating an ejection fraction ≥ 50% prior to the initiation of induction chemotherapy 9. For females of reproductive potential and males: Agree to abstain from sexual activity or use reliable contraception while undergoing treatment with chemotherapy and/or ACE inhibitors due to the risk of teratogenicity to the fetus. Exclusion Criteria: 1. Ongoing use of any beta blocker, ACEi, or angiotensin II receptor agonist (ARB) at the time of pre-enrollment screening. 2. Uncontrolled, intercurrent illnesses including but not limited to symptomatic unstable angina pectoris, cardiac arrhythmias not well controlled with medications, myocardial infarction in the 6 months preceding registration or psychiatric illness/social situations that would limit compliance with study requirements as determined by the study personnel, all at the discretion of the treating oncologist. 3. Patient receiving concurrent investigational agents, or those who have received an investigational agent within one week of registration. Exception - Participants may receive concurrent investigational agents, or have done so within one week of registration if: * The side effects of the drug are well studied and well known AND * The drug is not known to be cardioprotective or cardiotoxic 4\. Females who are pregnant or lactating. 5\. Life-threatening illnesses other than AML, uncontrolled medical conditions or organ system dysfunction that, in the investigator's opinion, could compromise the patient's safety or study outcomes. 6\. Active, untreated and/or severe infections as determined by the treating oncologist. 7\. History of hematopoietic stem cell transplant (HSCT) with active graft vs host disease, immunosuppression other than low-dose prednisone (≤ 5mg) or calcineurin inhibitors within the four weeks preceding registration 8 Moderate or severe mitral or aortic valve disease, as determined by echocardiography 9\. Congestive heart failure as clinically diagnosed by treating oncologist at the time of presentation for induction chemotherapy, or documented diagnosed by a previous physician. 10\. History of (repaired or unrepaired) congenital heart disease that precludes recommendation for or administration of additional anthracyclines 11\. Significant liver disease, including cirrhosis or history of transplant or hepatorenal syndrome) 12\. Bradycardia (defined as baseline resting heart rate ≤ 60 beats per minute) or third degree atrioventricular heart block at presentation for induction chemotherapy. 13\. Baseline resting systolic blood pressure \< 95mmHg at presentation for induction chemotherapy. 14\. Documented allergy to beta blockers or ACE inhibitors.
Study sites (1)
VA
- University of Virginia · Charlottesville, VA 22903Cory Caldwell · Study contact · 434-297-4182 · CJC2P@uvahealth.orgAvani Hopkins · Study contact · AJH7JQE@uvahealth.orgMichael Keng, MD · Principal investigatorMore trials in Charlottesville