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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Percentage of patients experiencing a decrease in left ventricular ejection fraction (LVEF)
研究概览
简要总结
This phase II trial studies how well dexrazoxane hydrochloride works in preventing heart-related side effects of chemotherapy in participants with blood cancers, such as acute myeloid leukemia, myelodysplastic syndrome, chronic myeloid leukemia, and myeloproliferative neoplasms. Chemoprotective drugs, such as dexrazoxane hydrochloride, may protect the heart from the side effects of drugs used in chemotherapy, such as cladribine, idarubicin, cytarabine, and gemtuzumab ozogamicin, in participants with blood cancers.
详细描述
PRIMARY OBJECTIVES:
I. To estimate the percentage of patients experiencing a decrease in left ventricular ejection fraction (LVEF) of 10 percent from baseline or decrease in LVEF below the normal limit of 50% during treatment with dexrazoxane (dexrazoxane hydrochloride) combined with cladribine, idarubicin, cytarabine, and Mylotarg (gemtuzumab ozogamicin) within the first 6-months of treatment.
SECONDARY OBJECTIVES:
I. To estimate the incidence of these cardiac symptoms while on dexrazoxane combined with idarubicin-based treatment: clinical heart failure, exertional dyspnea, orthopnea, S3 gallop, acute coronary syndrome, acute pulmonary edema and life-threatening arrhythmias.
II. To assess and monitor the change of troponin I (while still standard of care at MD Anderson) and high-sensitivity troponin T during treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Supportive care (dexrazoxane hydrochloride, chemotherapy)
See detailed description.
干预措施: Dexrazoxane Hydrochloride (Drug)
Supportive care (dexrazoxane hydrochloride, chemotherapy)
See detailed description.
干预措施: Idarubicin (Drug)
Supportive care (dexrazoxane hydrochloride, chemotherapy)
See detailed description.
干预措施: Cladribine (Drug)
Supportive care (dexrazoxane hydrochloride, chemotherapy)
See detailed description.
干预措施: Cytarabine (Drug)
Supportive care (dexrazoxane hydrochloride, chemotherapy)
See detailed description.
干预措施: Gemtuzumab Ozogamicin (Drug)
结局指标
主要结局
Percentage of patients experiencing a decrease in left ventricular ejection fraction (LVEF)
时间窗: Baseline up to 6 months
Will assess a decrease in LVEF of 10 percent from baseline or decrease in LVEF below the normal limit of 50% during treatment with dexrazoxane hydrochloride combined with cladribine, idarubicin, cytarabine, and gemtuzumab ozogamicin.
次要结局
- Incidence of adverse events(Up to 1 year)
- Incidence of cardiac symptoms(Up to 1 year)
- Event-free survival (Cohorts 1-3)(Up to 1 year)
- Assessment of change in troponin I and high-sensitivity troponin T(Up to 1 year)
- Overall response (Cohorts 1-3)(Up to 1 year)
- Overall survival (Cohorts 1-3)(Up to 1 year)
- Complete remission (CR) /complete remission with incomplete blood count recovery (CRi) rates (Cohorts 1-3)(Up to 1 year)
- Remission duration (Cohorts 1-3)(Up to 1 year)
- Recurrence-free survival(Up to 6 months)