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Cardioprotection in AML (AML 001)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04977180
Recruitment Status : Recruiting
First Posted : July 26, 2021
Last Update Posted : July 6, 2022
Sponsor:
Information provided by (Responsible Party):
Michael Keng, MD, University of Virginia

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.


Condition or disease Intervention/treatment Phase
AML Acute Myeloid Leukemia Drug: Cardioprotection Phase 2

Detailed Description:

Participants will know which group they are assigned to, and if someone in the group not receiving the preventive drugs needs these drugs for their clinical care, they will be able to receive them.

Participants in both groups will receive the standard clinical care medicines and lab tests for their AML. Everyone will have electrocardiograms (also called ECGs or EKGs) and echocardiograms before and at multiple timepoints during the study. They will also have a special blood test to see their levels of troponin, a protein that helps with muscle contractions in your heart. All participants will complete questionnaires at a few timepoints during the study to measure their quality of life. Participants in the preventive beta blocker and ACEi group will take these drugs when they're in the hospital and at home, keeping a diary of when they take it when they're at home.

The hypothesis of the study is that taking a beta blocker and ACEi during initial therapy for AML and through about 90 days after they last take an anthracycline will prevent the development of this heart problem.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: 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
Actual Study Start Date : March 4, 2022
Estimated Primary Completion Date : January 1, 2025
Estimated Study Completion Date : September 1, 2025


Arm Intervention/treatment
Experimental: Treatment arm (beta blocker and ACE inhibitor)
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
Drug: Cardioprotection
Preventive beta blocker (metoprolol or carvedilol) and an ACE inhibitor (lisinopril)

No Intervention: Standard Clinical Care
Participants will receive standard clinical care, but will also undergo regular assessments via ECG/EKG and echocardiogram, and to measure troponin levels



Primary Outcome Measures :
  1. Left ventricular ejection fraction (LVEF) [ Time Frame: Baseline through 90 days after first day of last cycle of anthracycline (usually up to 6 months later) ]
    As determined by echocardiogram


Secondary Outcome Measures :
  1. Congestive heart failure [ Time Frame: Baseline through 90 days after first day of last cycle of anthracycline (usually up to 6 months later) ]
    As diagnosed by treating physician

  2. Changes in quality of life [ Time Frame: Baseline through 90 days after first day of last cycle of anthracycline (usually up to 6 months later) ]
    As measured by the FACT-Leu questionnaire

  3. Global longitudinal strain [ Time Frame: Baseline through 90 days after first day of last cycle of anthracycline (usually up to 6 months later) ]
    As measured by echocardiogram

  4. Troponin levels [ Time Frame: Baseline through 90 days after first day of last cycle of anthracycline (usually up to 6 months later) ]
    Frequency of elevation in troponin and average troponin



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  10. 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. 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.
  6. 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.
  7. Radiographic evidence of extramedullary disease
  8. Acute Promyelocytic Leukemia (APL) or AML with active central nervous system (CNS) involvement.
  9. Active, untreated and/or severe infections as determined by the treating oncologist.
  10. Active and uncontrolled HIV infection, defined as infection possessing a PCR-detectable viral load
  11. Active infection with the Hepatitis B Virus, defined as having a positive Hepatitis B surface antigen or PCR-detectable viral load
  12. Active infection with the Hepatitis C Virus, defined as having a PCR-detectable viral load.
  13. 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
  14. Moderate or severe mitral or aortic valve disease, as determined by echocardiography
  15. Congestive heart failure as clinically diagnosed by treating oncologist at the time of presentation for induction chemotherapy, or documented diagnosed by a previous physician.
  16. History of (repaired or unrepaired) congenital heart disease
  17. Significant liver disease, including cirrhosis or history of transplant or hepatorenal syndrome)
  18. Bradycardia (defined as baseline resting heart rate ≤ 60 beats per minute) or third degree atrioventricular heart block at presentation for induction chemotherapy.
  19. Baseline resting systolic blood pressure < 95mmHg at presentation for induction chemotherapy.
  20. Documented allergy to beta blockers or ACE inhibitors.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04977180


Contacts
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Contact: Kelly Reed 434-297-7783 YVY8GE@hscmail.mcc.virginia.edu
Contact: Cory Caldwell 434-297-4182 CJC2P@hscmail.mcc.virginia.edu

Locations
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United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22903
Contact: Kelly Reed    434-297-7783    YVY8GE@hscmail.mcc.virginia.edu   
Contact: Cory Caldwell    4342974182    CJC2P@hscmail.mcc.virginia.edu   
Principal Investigator: Michael Keng, MD         
Sponsors and Collaborators
University of Virginia
Investigators
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Principal Investigator: Michael Keng UVA
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Responsible Party: Michael Keng, MD, Associate Professor, University of Virginia
ClinicalTrials.gov Identifier: NCT04977180    
Other Study ID Numbers: HSR210151
First Posted: July 26, 2021    Key Record Dates
Last Update Posted: July 6, 2022
Last Verified: July 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Michael Keng, MD, University of Virginia:
cardioprotection
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms