Using dexrazoxane to protect the heart during chemotherapy for blood cancers

Cardioprotection With Dexrazoxane in Acute Myeloid Leukemia (AML), High-Risk Myelodysplastic Syndrome (MDS), Myeloid Blast Phase of Chronic Myeloid Leukemia (CML), Ph+ AML, and Myeloid Blast Phase of Myeloproliferative Neoplasms

This study is testing if a drug called dexrazoxane can help protect the hearts of people with blood cancers from damage caused by chemotherapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 12 Years and up
• Sex: All
• Sponsor: M.D. Anderson Cancer Center (Academic / other)
• Drugs / interventions: chemotherapy, gemtuzumab
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT03589729 on ClinicalTrials.gov

What this trial studies

This phase II trial investigates the effectiveness of dexrazoxane hydrochloride in preventing heart-related side effects caused by chemotherapy in patients with blood cancers such as acute myeloid leukemia and high-risk myelodysplastic syndrome. The study aims to measure the percentage of patients experiencing a significant decrease in heart function during treatment with chemotherapy drugs like cladribine and idarubicin. Secondary objectives include monitoring cardiac symptoms and assessing the safety profile of dexrazoxane. The trial also explores the potential benefits of metal chelation effects from dexrazoxane in conjunction with chemotherapy.

Who should consider this trial

Good fit: Ideal candidates include patients diagnosed with acute myeloid leukemia, high-risk myelodysplastic syndrome, or chronic myeloid leukemia in blast phase with a baseline left ventricular ejection fraction of 50% or higher.

Not a fit: Patients with pre-existing heart conditions or those with a baseline left ventricular ejection fraction below 50% may not benefit from this study.

Why it matters

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

How similar studies have performed: Other studies have shown promise in using chemoprotective agents like dexrazoxane, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* Baseline left ventricular ejection fraction (LVEF) is greater than or equal to 50% by echocardiography (echo) or multigated acquisition (MUGA) scan.
* Patients of child bearing potential should use contraception.
* Patients with a diagnosis of acute myeloid leukemia (AML), or high risk myelodysplastic syndrome (MDS) (\>= 10% blasts or International Prognostic Scoring System \[IPSS\] \>= intermediate-2) or high-risk myeloproliferative neoplasm will be eligible.
* Patients with untreated or previously untreated chronic myeloid leukemia (CML) in myeloid blast phase or (Philadelphia chromosome-positive (Ph+) AML are also eligible.
* Patients with myeloproliferative neoplasms in blast phase will be eligible.
* Patients with isolated extramedullary myeloid neoplasm will be eligible.
* Patients with active CNS (central nervous system) disease are eligible.
* Bilirubin \< 2mg/dL.
* AST (aspartate aminotransferase) and/or ALT (alanine aminotransferase) \< 3 x ULN (upper limit of normal) - or \< 5 x ULN if related to leukemic involvement.
* Creatinine \< 1.5 x ULN.
* Hyperbilirubinemia is allowed if due to Gilbert's hyperbilirubinemia.
* A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.
* Women of childbearing potential and men must agree to use contraception prior to study entry and for the duration of study participation.
* Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient or his legally authorized representative is required prior to their enrollment on the protocol.
* Prior therapy for any of the cohorts may include with hydroxyurea, rescue doses of cytarabine, various combination-chemotherapy regimens, hematopoietic growth factors, azacytidine, decitabine, ATRA (all-trans retinoic acid).
* Cohort 1: Frontline cohort patients are eligible in the frontline cohort if they are untreated or previously treated already in CR if they received 3 or fewer cycles of previous chemotherapy (including either 1 induction and 2 consolidations or 2 inductions and 1 consolidation).
* Cohort 2: Salvage cohort in 1st and 2nd salvage patients are eligible in the salvage cohort 2 if they have active disease after first or second relapse or if they are in CR after previously documented first or second relapse as long as they if they have received 3 or fewer cycles of chemotherapy to achieve the most current CR.
* Cohort 3: Salvage cohort in 3rd salvage and beyond patients may be eligible in salvage cohort 3 if they have active disease after 3rd or greater relapse or if they are in CR after a previously documented relapse (3rd or greater), but may have only received 3 or fewer cycles of chemotherapy to achieve the most current CR.
* Cohort 4: Maintenance cohort: Patients in CR who are considered by treating physician to benefit from maintenance therapy are eligible for maintenance therapy with dexrazoxane combined with idarubicin plus cytarabine.

Exclusion Criteria:

* Any condition, including the presence of laboratory abnormalities, which judged by the investigator, places the patient at unacceptable risk.
* Active heart disease defined as: Unstable coronary syndromes, unstable or severe angina, recent myocardial infarction (MI) within 6 months.
* Decompensated heart failure (HF).
* Clinically significant arrhythmias.
* Severe valvular disease.
* History of coronary artery disease (CAD).
* Pregnant women are excluded from this study because the agents used in this study have the potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with the chemotherapy agents, breastfeeding should also be avoided.
* Psychiatric illness/social situations that would limit compliance with study requirements per the judgment of the investigator.
* Patient with documented hypersensitivity to any of the components of the chemotherapy program.
* Men and women of childbearing potential who do not practice contraception.

Where this trial is running

Houston, Texas

• M D Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Maro Ohanian — M.D. Anderson Cancer Center
• Study coordinator: Maro Ohanian

Conditions Acute Myeloid Leukemia; Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Blasts 10 Percent or More of Bone Marrow Nucleated Cells; High Risk Myelodysplastic Syndrome; Myeloid Sarcoma; Myeloproliferative Neoplasm; Philadelphia Chromosome Positive