Cardioprotective Drugs for Acute Myeloid Leukemia
(AML 001 Trial)
Recruiting in Palo Alto (17 mi)
Overseen byMichael Keng, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Virginia
Must not be taking: Beta blockers, ACE inhibitors
Disqualifiers: Pregnancy, Congestive heart failure, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?
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.
Will I have to stop taking my current medications?
If you are currently using any beta blockers, ACE inhibitors, or angiotensin II receptor blockers, you will need to stop taking them before joining this trial. The trial does not specify about other medications, so it's best to discuss your current medications with the study team.
What data supports the effectiveness of cardioprotective drugs for preventing heart damage in patients with acute myeloid leukemia?
Research shows that cardioprotective drugs like beta-blockers and ACE inhibitors can help prevent heart damage caused by certain cancer treatments. These drugs have been found to reduce heart problems in patients receiving chemotherapy, which suggests they might also help protect the heart in acute myeloid leukemia patients.12345
Is it safe to use cardioprotective drugs like ACE inhibitors and beta-blockers in humans?
How is the cardioprotective drug treatment for acute myeloid leukemia different from other treatments?
This treatment is unique because it uses beta blockers and ACE inhibitors, which are typically used to protect the heart from damage, to prevent heart problems caused by chemotherapy in acute myeloid leukemia patients. Unlike traditional cancer treatments that focus solely on attacking cancer cells, this approach aims to protect the heart from the harmful side effects of chemotherapy.13568
Eligibility Criteria
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.Inclusion Criteria
I agree to use birth control or abstain from sex during my treatment.
I can take care of myself and am up and about more than half of my waking hours.
I am 18 or older and have been recently diagnosed with AML.
See 6 more
Exclusion Criteria
I have been diagnosed with congestive heart failure by my oncologist.
I do not have any severe or untreated infections.
I have moderate or severe heart valve disease.
See 11 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Induction Treatment
Participants receive induction therapy for AML, including daunorubicin and potentially beta blocker and ACE inhibitor for cardioprotection
6 weeks
Multiple visits for chemotherapy administration and monitoring
Consolidation Treatment
Continuation of AML treatment and cardioprotective measures, with regular assessments via ECG/EKG and echocardiogram
Up to 6 months
Regular visits for treatment and monitoring
Follow-up
Participants are monitored for safety and effectiveness after treatment, including assessments of heart function and quality of life
90 days after last anthracycline cycle
Regular follow-up visits
Treatment Details
Interventions
- Cardioprotection (ACE Inhibitor and Beta Blocker)
Trial OverviewThe 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.
Participant Groups
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). 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.
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
Cardioprotection is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Beta blockers and ACE inhibitors for:
- Heart failure
- Hypertension
- Prevention of anthracycline-induced cardiotoxicity
🇪🇺 Approved in European Union as Beta blockers and ACE inhibitors for:
- Heart failure
- Hypertension
- Prevention of anthracycline-induced cardiotoxicity
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of VirginiaCharlottesville, VA
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Who Is Running the Clinical Trial?
University of VirginiaLead Sponsor
References
Prevention of chemotherapy-induced left ventricular dysfunction with enalapril and carvedilol: rationale and design of the OVERCOME trial. [2018]The current treatment of hematologic malignancies includes diverse potentially cardiotoxic chemotherapy agents, including high-dose myeloablative regimens used in autologous hematopoietic stem cell transplantation (HSCT). Many of these treatments could induce left ventricular dysfunction (LVD), and limit their efficacy. Angiotensin-converting enzime inhibitors and beta-blockers prevent LVD and prolong survival after infarction, and recent animal and pilot clinical studies suggest that they can prevent the development of chemotherapy-induced cardiac toxicity.
Management of cardiovascular health in acute leukemia: a national survey. [2020]Cardiovascular (CV) disease is a common comorbidity in acute leukemia (AL) patients and can be worsened by the use of anthracyclines. Interruptions and underutilization of CV medications during AL treatments may negatively impact the CV health of these patients. A 30-question electronic survey was distributed to Canadian hematologists who treat adults with AL to determine the frequency, timing and rationale for interruptions in statins, antiplatelets and angiotensin antagonists in patients undergoing intensive chemotherapy. Strategies for mitigating anthracycline cardiotoxicity, methods of establishing baseline CV risk and utilization of clinical pharmacists were also assessed. Results indicate that it is common for AL patients undergoing intensive chemotherapy to require CV medication interruptions. This highlights the need for collaboration between hematology and cardiology healthcare teams and utilization of multidisciplinary healthcare professionals to improve CV care during AL.
New perspectives on treatment strategies for patient with acute myeloid leukemia and complex karyotype abnormalities after percutaneous coronary intervention: A case report. [2022]Acute myeloid leukemia (AML), in patients with coronary heart disease (CHD) and treated percutaneous coronary intervention (PCI), is rarely seen in clinic. There are few similar cases reported, and there are no evidence-based medicine guidelines for the treatment.
Effect of Dexrazoxane on Left Ventricular Systolic Function and Treatment Outcomes in Patients With Acute Myeloid Leukemia: A Report From the Children's Oncology Group. [2021]To determine whether dexrazoxane provides effective cardioprotection during frontline treatment of pediatric acute myeloid leukemia (AML) without increasing relapse risk or noncardiac toxicities of the chemotherapy regimens.
Prevention of anthracycline-induced cardiotoxicity: a systematic review and meta-analysis. [2021]Anthracyclines are extensively used in oncologic patients, in particular for breast cancer and hematological malignancies. Cardiac injury is a potentially dangerous side effect of these drugs. In this systematic review, we analyzed published randomized controlled trials (RCTs) to assess if potential cardioprotective drugs (i.e., renin-angiotensin-aldosterone system [RAAS] blockers and β-blockers) may prevent heart damage by anthracyclines. Studies were identified by electronic search of MEDLINE and EMBASE database until August 2020. The impact of cardioprotective drugs to prevent anthracyclines-induced cardiac injury was expressed as mean difference (MD) or odds ratio (OR) and 95% confidence intervals (95% CI). Statistical heterogeneity was assessed with the I2 statistic. Twelve RCTs for a total of 1.035 cancer patients treated with anthracyclines were included. RAAS blockers, β-blockers, and aldosterone antagonists showed a statistically significant benefit in preventing left ventricular ejection fraction (LVEF) reduction (MD 3.57, 95% CI 1.04, 6.09) in 11 studies. A non-statistically significant difference was observed in preventing E/A velocity decrease (MD 0.09, 95% CI 0.00, 0.17; 9 studies), left ventricular end-systolic diameter (LVESD) increase (MD - 0.88, 95% CI, - 2.75,0.99; 6 studies), left ventricular end-diastolic diameter (LVEDD) increase (MD -0.95, 95% CI - 2.67,0.76; 6 studies), and mitral A velocity decrease (MD - 1.42, 95% CI - 3.01,0.17; 4 studies). Heart failure was non-significantly reduced in the cardioprotective arm (OR 0.31, 95% CI 0.06, 1.59; 5 studies). Hypotension was non-significantly increased in the cardioprotective arm (OR 3.91, 95% CI 0.42, 36.46, 3 studies). Cardioprotective drugs reduce anthracycline-induced cardiac damage as assessed by echocardiographic parameters. The clinical relevance of this positive effect is still to be defined.
Protective Effects of ACEI/ARB on Left Ventricular Function in Anthracycline-Induced Chronic Cardiotoxicity: A Meta-Analysis of Randomized Controlled Trials. [2021]Cardiotoxicity is an important side effect of anthracycline. Cardioprotective drugs for anthracycline remain inconclusive. We attempted to determine the role of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-receptor blockers (ARB) in the prevention of anthracycline-induced cardiotoxicity.
[AT1 blockers - comparability with ACE inhibitors]. [2018]The reduction in overall mortality, cardiovascular mortality and the occurrence of myocardial infarction in patients treated with AT1 blockers is comparable with the use of ACE inhibitors. In addition, there is a lower proportion of AT1 blockers withdrawal of treatment due to adverse reactions.Key words: ACE inhibitors - AT1 blockers - cardioprotection - hypertension - renin-angiotensin-aldosteron system.
Heart failure from cancer therapy: can we prevent it? [2021]Conventional cytotoxic chemotherapy is still among the most effective treatment options for many types of cancer. However, cardiotoxicity, notably the decrease in left ventricular function under these regimens, can impair prognosis. Thus, prevention and treatment of cardiotoxicity are crucial. The present meta-analysis aims to assess the efficacy of beta-blockers or angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs) for prevention of cardiotoxicity.