Protecting the heart during treatment for acute myeloid leukemia

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

This study is testing if giving heart-protecting medications to people with acute myeloid leukemia who are being treated with daunorubicin can help prevent heart damage during their treatment.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 70 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Virginia (Academic / other)
• Drugs / interventions: chemotherapy, prednisone
• Locations: 1 site (Charlottesville, Virginia)
• Trial ID: NCT04977180 on ClinicalTrials.gov

What this trial studies

This study investigates the potential cardioprotective effects of beta blockers and ACE inhibitors in patients undergoing treatment for acute myeloid leukemia (AML) with the drug daunorubicin. Participants will be randomly assigned to receive either these preventive medications or standard care without them. The study aims to assess the frequency of heart damage caused by anthracycline chemotherapy and will monitor heart function through electrocardiograms, echocardiograms, and blood tests. Additionally, quality of life will be evaluated through questionnaires at various time points during the study.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with newly diagnosed acute myeloid leukemia who are planning to receive anthracycline-based induction therapy.

Not a fit: Patients who are not newly diagnosed with AML or those who are not planning to receive anthracycline therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could significantly reduce the risk of heart damage in AML patients undergoing chemotherapy.

How similar studies have performed: While the cardioprotective use of beta blockers and ACE inhibitors has been explored in other populations, this specific approach in AML patients is novel and has not been extensively tested.

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.

Where this trial is running

Charlottesville, Virginia

• University of Virginia — Charlottesville, Virginia, United States (Recruiting)

Study contacts

• Principal investigator: Michael Keng, MD — Uva
• Study coordinator: Cory Caldwell, RN

Conditions AML; Acute Myeloid Leukemia; cardioprotection