Phase I/II Randomized Study of Clofarabine, Idarubicin, and Cytarabine (CIA) Versus Fludarabine, Idarubicin, and Cytarabine (FLAI) in Acute Myelogenous Leukemia and High-Risk Myelodysplastic Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 282
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Clofarabine, Idarubicin, and Cytarabine
研究概览
简要总结
The goal of this clinical research study is to learn if the combination of clofarabine, idarubicin, and cytarabine, or the combination of fludarabine, idarubicin, and cytarabine can help control Acute myeloid leukemia (AML) and Myelodysplastic syndromes (MDS). The safety of these study drug combinations will also be studied.
详细描述
The Study Drugs:
Clofarabine is designed to interfere with the growth and development of cancer cells.
Idarubicin is designed to cause breaks in both strands of DNA (the genetic material of cells). This may cause the cancer cells to die.
Cytarabine and Fludarabine are designed to insert themselves into the DNA of cancer cells and stop the DNA from repairing itself.
Study Groups:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Sign an Institutional Review Board (IRB)-approved informed consent document.
- •Patients above the age of 60 only with principal investigator (PI) approval
- •Diagnosis of newly diagnosed AML [other than acute promyelocytic leukemia (APL)] or high-risk (intermediate-2 or high by International Prostate Symptom Score (IPSS) or > 10% blasts, including CMML) MDS. Prior therapy with hydrea and the use of a single or a two day dose of cytarabine (up to 3 g/m2) for emergency use up to 24 hours prior to start of study therapy is allowed. Prior therapy for MDS or other AHD is not allowed.
- •Eastern Cooperative Oncology Group (ECOG) performance status of </= 3 at study entry.
- •Organ function as defined below (unless due to leukemia): Serum creatinine </= 3 mg/dL Total bilirubin </= 2.5 mg/dL , Alanine aminotransferase (ALT) (SGPT) </= 3 * upper limit of normal (ULN) or </= 5 * ULN if related to disease.
- •Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days and must agree to practice acceptable contraceptive methods. Men must agree not to father a child and agree to use a condom if his partner is of child bearing potential.
- •Cardiac ejection fraction >/= 40% (by either cardiac echo or multiple gated acquisition scan (MUGA) scan). Documentation of recent (</= 6 months from screening) outside reports is acceptable.
排除标准
- •Breast feeding females
- •Patients with uncontrolled active infections (viral, bacterial, and fungal are not eligible).
- •Patients with active secondary malignancy will not be eligible.
研究组 & 干预措施
Clofarabine + Idarubicin + Cytarabine
Phase I: Clofarabine Starting dose 15 mg/m2 by vein for 5 days (days 1-5) + Idarubicin 10 mg/m2 by vein on day 1-3 + Cytarabine 1 g/m2 by vein on day 1-5.
干预措施: Clofarabine (Drug)
Clofarabine + Idarubicin + Cytarabine
Phase I: Clofarabine Starting dose 15 mg/m2 by vein for 5 days (days 1-5) + Idarubicin 10 mg/m2 by vein on day 1-3 + Cytarabine 1 g/m2 by vein on day 1-5.
干预措施: Idarubicin (Drug)
Clofarabine + Idarubicin + Cytarabine
Phase I: Clofarabine Starting dose 15 mg/m2 by vein for 5 days (days 1-5) + Idarubicin 10 mg/m2 by vein on day 1-3 + Cytarabine 1 g/m2 by vein on day 1-5.
干预措施: Cytarabine (Drug)
Clofarabine + Idarubicin + Cytarabine
Phase I: Clofarabine Starting dose 15 mg/m2 by vein for 5 days (days 1-5) + Idarubicin 10 mg/m2 by vein on day 1-3 + Cytarabine 1 g/m2 by vein on day 1-5.
干预措施: Fludarabine (Drug)
Group 1 CIA
Phase II, Group 1 CIA (Clofarabine + Idarubicin + Cytarabine): Clofarabine Maximum Tolerated Dose (MTD) based on Phase I by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5.
干预措施: Clofarabine (Drug)
Group 1 CIA
Phase II, Group 1 CIA (Clofarabine + Idarubicin + Cytarabine): Clofarabine Maximum Tolerated Dose (MTD) based on Phase I by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5.
干预措施: Idarubicin (Drug)
Group 1 CIA
Phase II, Group 1 CIA (Clofarabine + Idarubicin + Cytarabine): Clofarabine Maximum Tolerated Dose (MTD) based on Phase I by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5.
干预措施: Cytarabine (Drug)
Group 2 FLAI
Phase II, Group 2 FLAI (Fludarabine + Idarubicin + Cytarabine): Fludarabine 30 mg/m2 by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5.
干预措施: Idarubicin (Drug)
Group 2 FLAI
Phase II, Group 2 FLAI (Fludarabine + Idarubicin + Cytarabine): Fludarabine 30 mg/m2 by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5.
干预措施: Cytarabine (Drug)
Group 2 FLAI
Phase II, Group 2 FLAI (Fludarabine + Idarubicin + Cytarabine): Fludarabine 30 mg/m2 by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5.
干预措施: Fludarabine (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Clofarabine, Idarubicin, and Cytarabine
时间窗: 28 days
MTD is highest dose level in which \<2 patients of 6 develop first cycle dose limiting toxicities (DLT). Toxicity defined as any treatment-related grade 3 or greater non-hematological toxicities.
次要结局
- Response Rates of Clofarabine, Idarubicin, and Cytarabine (CIA) Versus Fludarabine, Idarubicin, and Cytarabine (FLAI)(12 months)
- Overall Survival(up to 2 years)
- Event-Free Survival (EFS) at 2 Years(Up to 2 years or until relapse/death)