What side effects are associated with this type of intervention?

Common treatments for Acute Myeloid Leukemia (AML) often include anthracyclines such as daunorubicin, which are associated with cardiotoxicity, potentially leading to heart failure. Preventive use of beta blockers and ACE inhibitors can help reduce this risk. Other side effects of AML treatments, including cytarabine and clofarabine, may include myelosuppression, leading to increased risk of infections, anemia, and bleeding. Gastrointestinal issues like nausea, vomiting, and diarrhea, as well as liver and kidney toxicity, are also common. Patients may experience fatigue, mucositis, and hair loss as well.

What prior FDA approvals exist?

The FDA has approved several treatments for Acute Myeloid Leukemia (AML), including anthracyclines like daunorubicin, which are standard chemotherapy agents but carry a risk of cardiotoxicity. To mitigate this risk, beta blockers and ACE inhibitors are being studied for their preventive use. Other FDA-approved treatments for AML include hypomethylating agents such as azacitidine and decitabine, which are used for patients who are not candidates for intensive chemotherapy. Additionally, targeted therapies like venetoclax, which inhibits the BCL2 protein, are used in combination with low-dose cytarabine for certain AML patients.

What other types of research exist?

As of 2024, promising novel alternatives to beta blockers and ACE inhibitors for preventing anthracycline-induced cardiotoxicity in AML patients include the use of cardioprotective agents such as dexrazoxane, which has shown efficacy in reducing cardiotoxicity. Additionally, ongoing research into the use of statins, such as atorvastatin and rosuvastatin, and the potential role of angiotensin receptor-neprilysin inhibitors (ARNIs) like sacubitril/valsartan, may offer new preventive strategies. These alternatives are being explored for their ability to mitigate cardiac damage while maintaining the efficacy of anthracycline chemotherapy.

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ACE Inhibitor and Beta Blocker

Cardioprotective Drugs for Acute Myeloid Leukemia (AML 001 Trial)

Phase 2

Recruiting

Led By Michael Keng

Research Sponsored by University of Virginia

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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 for females of reproductive potential and males

ECOG performance status must be ≤ 2

Must not have

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

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

Timeline

Screening 3 weeks

Treatment Varies

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

Awards & highlights

No Placebo-Only Group

Summary

This trial tests if taking beta blockers and ACE inhibitors can prevent heart damage in AML patients receiving daunorubicin chemotherapy. These medications help protect the heart by reducing stress and preventing damage. The study will compare heart health and quality of life between those who take these medications and those who do not.

Who is the study for?

Adults over 18 with newly-diagnosed Acute Myeloid Leukemia (AML) who are about to start or have just started induction therapy without anthracycline can join. They must be able to take oral meds, have good organ function, and an ejection fraction ≥ 50%. Women of childbearing age and men must use contraception. Can't join if already using heart meds like beta blockers or ACEi, have severe illnesses/heart issues, pregnant/lactating women, or those with certain medical conditions.

What is being tested?

The trial is testing whether taking a beta blocker and ACE inhibitor before starting chemotherapy can prevent heart damage caused by the drug daunorubicin in AML patients. Participants will either receive these drugs as prevention or not. The study measures how often heart damage occurs and monitors overall heart health and quality of life.

What are the potential side effects?

Potential side effects from beta blockers may include fatigue, cold hands/feet, weight gain; while ACE inhibitors might cause coughing, increased blood potassium levels, low blood pressure, dizziness. Side effects vary among individuals.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I agree to use birth control or abstain from sex during my treatment.

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I can take care of myself and am up and about more than half of my waking hours.

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I am 18 or older and have been recently diagnosed with AML.

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My organ functions are within normal ranges according to recent tests.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been diagnosed with congestive heart failure by my oncologist.

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I do not have any severe or untreated infections.

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I have moderate or severe heart valve disease.

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I don't have any severe illnesses or uncontrolled conditions that could risk my safety or affect the study.

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I am currently taking medication for blood pressure or heart conditions.

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I am not pregnant or breastfeeding.

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I have a very slow heartbeat or a specific heart block.

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I have a serious liver condition, such as cirrhosis, or have had a liver transplant.

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I have a heart condition that prevents me from receiving certain chemotherapy drugs.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline through 90 days after first day of last cycle of anthracycline (usually up to 6 months later)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline through 90 days after first day of last cycle of anthracycline (usually up to 6 months later)

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline through 90 days after first day of last cycle of anthracycline (usually up to 6 months later) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Left ventricular ejection fraction (LVEF)

Secondary study objectives

Changes in quality of life

Congestive heart failure

Global longitudinal strain

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Treatment arm (beta blocker and ACE inhibitor)Experimental Treatment1 Intervention

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). They will also undergo regular assessments via ECG/EKG and echocardiogram, and to measure troponin levels

Group II: Standard Clinical CareActive Control1 Intervention

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

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Acute Myeloid Leukemia (AML) include anthracyclines like daunorubicin and cytarabine. These drugs work by intercalating DNA and inhibiting topoisomerase II, causing DNA damage and inducing apoptosis in leukemic cells. However, anthracyclines can lead to cardiotoxicity, which is why preventive treatments such as beta blockers and ACE inhibitors are important. These cardioprotective agents reduce oxidative stress and improve cardiac function, helping AML patients tolerate and complete their chemotherapy regimen more effectively.

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