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 (AML 001)

  • STATUS
    Recruiting
  • End date
    Sep 1, 2025
  • participants needed
    28
  • sponsor
    University of Virginia
Updated on 23 October 2022
hydroxyurea
ejection fraction
gilbert's syndrome
induction chemotherapy
daunorubicin
anthracyclines

Summary

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.

Description

Participants will know which group they are assigned to, and if someone in the group not receiving the preventive drugs needs these drugs for their clinical care, they will be able to receive them.

Participants in both groups will receive the standard clinical care medicines and lab tests for their AML. 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. Participants in the preventive beta blocker and ACEi group will take these drugs when they're in the hospital and at home, keeping a diary of when they take it when they're at home.

The hypothesis of the study is that taking a beta blocker and ACEi during initial therapy for AML and through about 90 days after they last take an anthracycline will prevent the development of this heart problem.

Details
Condition AML, Acute Myeloid Leukemia
Treatment Cardioprotection, Cardioprotection
Clinical Study IdentifierNCT04977180
SponsorUniversity of Virginia
Last Modified on23 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Signed informed consent obtained prior to conducting any study-specific screening procedures
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
Age ≥ 18 years old with newly-diagnosed Acute Myeloid Leukemia (AML)
ECOG performance status must be ≤ 2
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
Adequate organ function as evidenced by the following laboratory findings
Total bilirubin ≤ 1.5 x upper limit of normal (ULN) or < 3 x ULN for patients with Gilbert's Syndrome
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
Creatinine clearance > 60 mL/min
Ability to take oral medication and a willingness to adhere to the beta blocker and
lisinopril regimen
Echocardiogram demonstrating an ejection fraction ≥ 50% prior to the initiation of induction chemotherapy
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

Ongoing use of any beta blocker, ACEi, or angiotensin II receptor agonist (ARB) at the time of pre-enrollment screening
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
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
Active, untreated and/or severe infections as determined by the treating
oncologist
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
History of (repaired or unrepaired) congenital heart disease 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
Baseline resting systolic blood pressure < 95mmHg at presentation for induction
chemotherapy
Documented allergy to beta blockers or ACE inhibitors
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