Dexrazoxane Hydrochloride in Preventing Heart-Related Side Effects of Chemotherapy in Patients with Blood Cancers

Inclusion Criteria

• 12 years or older
• 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 treated 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 < 2 mg/dL (unless due to leukemia/hematologic malignancy).
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN) – or < 5 x ULN if related to leukemic involvement).
• Creatinine < 1.5 x ULN unless due to leukemia/hematologic malignancy.
• Hyperbilirubinemia is allowed if due to Gilbert’s hyperbilirubinemia.
• A negative urine pregnancy test or blood test for pregnancy 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 but is not limited: hydroxyurea, rescue doses of cytarabine, various combination-chemotherapy regimens, targeted therapy, hematopoietic growth factors, azacytidine, decitabine, all-trans retinoic acid (ATRA).
• Cohort 1 (Frontline Cohort): Patients are eligible in the frontline cohort if they are untreated or previously treated and 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 with relapsed/refractory disease in 1st or 2nd salvage are eligible, including patients who are relapsed or refractory after 1 or 2 prior regimens.
• 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 with relapsed/refractory disease in 3rd salvage and beyond are eligible, including patients who are relapsed or refractory after 3 or more prior regimens.
• 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/CRi who are considered by treating physician to benefit from maintenance therapy are eligible for maintenance therapy with dexrazoxane combined with: * Mylotarg, low dose cytarabine, idarubicin OR * Mylotarg, idarubicin, azacytidine (75 mg/m2 subcutaneous [SQ] or IV over 10-40 minutes days 1-3 each cycle) OR * Mylotarg, idarubicin, decitabine (20 mg/m2 IV over 1 hour days 1-3 each cycle)

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.