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
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.
• 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.