Cardioprotection in AML

NCT04977180 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HSR210151
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

AML; Acute Myeloid Leukemia

Keywords

cardioprotection

Outcome Measures

Primary Outcomes (1)

• Left ventricular ejection fraction (LVEF)

  As determined by echocardiogram

  Baseline through 90 days after first day of last cycle of anthracycline (usually up to 6 months later)

Secondary Outcomes (4)

• Congestive heart failure

  Baseline through 90 days after first day of last cycle of anthracycline (usually up to 6 months later)

• Changes in quality of life

  Baseline through 90 days after first day of last cycle of anthracycline (usually up to 6 months later)

• Global longitudinal strain

  Baseline through 90 days after first day of last cycle of anthracycline (usually up to 6 months later)

• Troponin levels

  Baseline through 90 days after first day of last cycle of anthracycline (usually up to 6 months later)

Study Arms (2)

Treatment arm (beta blocker and ACE inhibitor)

EXPERIMENTAL

Participants will receive a beta blocker (either metoprolol or carvedilol) and an ACE inhibitor (lisinopril) at standard doses based on tolerance starting from when they start induction therapy for AML through 90 days after the first day of the last cycle of therapy that includes an anthracycline (whether that is in the induction, re-induction, or consolidation phase of treatment). If participants are unable to tolerate either beta blocker (e.g., heart rate is low at baseline or is lowered to an unsafe level with the beta blocker), no beta blocker may be administered as part of this study treatment. They will also undergo regular assessments via ECG/EKG and echocardiogram, and to measure troponin levels.

Drug: Cardioprotection

Standard Clinical Care

NO INTERVENTION

Participants will receive standard clinical care, but will also undergo regular assessments via ECG/EKG and echocardiogram, and to measure troponin levels

Interventions

Cardioprotection DRUG

Preventive beta blocker (metoprolol or carvedilol) and an ACE inhibitor (lisinopril)

Treatment arm (beta blocker and ACE inhibitor)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• \. Females who are pregnant or lactating.
• \. 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
• Moderate or severe mitral or aortic valve disease, as determined by echocardiography
• \. 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 that precludes recommendation for or administration of additional anthracyclines
• \. Significant liver disease, including cirrhosis or history of transplant or hepatorenal syndrome)
• \. Bradycardia (defined as baseline resting heart rate ≤ 60 beats per minute) or third degree atrioventricular heart block at presentation for induction chemotherapy.

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22903, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Michael Keng, MD

  UVA

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cory Caldwell, RN

CONTACT

434-297-4182; CJC2P@uvahealth.org

Avani Hopkins, RN

CONTACT

AJH7JQE@uvahealth.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 19, 2021
• First Posted: July 26, 2021
• Study Start: March 4, 2022
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)