Cardioprotection in AML

• Status: Not yet recruiting
• Trial end date: 2025-05-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Virginia

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. Peripheral white blood cell (WBC) count < 30,000/µL. For those patients with a WBC count above this threshold who are requiring cytoreduction, hydroxyurea is permitted during screening and through Cycle 1, Day 7 in order to reduce WBC count to < 30,000/µL.

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. QT interval corrects to < 480ms on one electrocardiogram (ECG) at screening

9. Echocardiogram demonstrating an ejection fraction ≥ 50% prior to the initiation of induction chemotherapy

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.

4. Females who are pregnant or lactating.

5. For females of reproductive potential: a negative pregnancy test is traditionally required prior to initiation of induction chemotherapy, due to the risk of teratogenicity to the fetus, and patients are advised to either abstain from sexual activity or use reliable contraception while undergoing treatment. All patients will additionally be counseled on the teratogenic effects of ACE inhibitors, in addition to their induction chemotherapy, and counseled to adhere to the recommendations outlined above.

6. History of other malignancies in the 12 months preceding registration with the exception of in-situ cancers, non-muscle invasive bladder cancer, prostate cancer basal or squamous cell skin cancers.

7. 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.

8. Radiographic evidence of extramedullary disease

9. Acute Promyelocytic Leukemia (APL) or AML with active central nervous system (CNS) involvement.

10. Active, untreated and/or severe infections as determined by the treating oncologist.

11. Active and uncontrolled HIV infection, defined as infection possessing a PCR-detectable viral load

12. Active infection with the Hepatitis B Virus, defined as having a positive Hepatitis B surface antigen or PCR-detectable viral load

13. Active infection with the Hepatitis C Virus, defined as having a PCR-detectable viral load.

14. 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

15. Moderate or severe mitral or aortic valve disease, as determined by echocardiography

16. Congestive heart failure as clinically diagnosed by treating oncologist at the time of presentation for induction chemotherapy, or documented diagnosed by a previous physician.

17. History of (repaired or unrepaired) congenital heart disease

18. Significant liver disease, including cirrhosis or history of transplant or hepatorenal syndrome)

19. Bradycardia (defined as baseline resting heart rate ≤ 60 beats per minute) or third degree atrioventricular heart block at presentation for induction chemotherapy.

20. Baseline resting systolic blood pressure < 95mmHg at presentation for induction chemotherapy.

21. Documented allergy to beta blockers or ACE inhibitors.