Phase I/II Study of Decitabine (DAC) Followed by Clofarabine, Idarubicin, and Cytarabine (CIA) in Acute Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 65
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Clofarabine
研究概览
简要总结
The goal of Phase I of this clinical research study is find the highest tolerable dose of clofarabine that can be given with decitabine, idarubicin, and cytarabine to patients with acute leukemia.
The goal of Phase II of this study is to learn if decitabine followed by the combination of clofarabine, idarubicin, and cytarabine can help to control acute leukemia. The safety of this drug combination will also be studied.
Decitabine and idarubicin are designed to damage the DNA (the genetic material of cells). This may cause cancer cells to die.
Clofarabine is designed to interfere with the growth and development of cancer cells.
Cytarabine is designed to insert itself into DNA and stop the DNA from repairing itself.
详细描述
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 3 groups of 6 participants will be enrolled in the Phase I portion of the study. Up to 74 participants will be enrolled in Phase II.
Phase I:
If you are enrolled in the Phase I portion, the number of days of clofarabine you receive will depend on when you joined this study. The first group of participants will receive clofarabine for 4 days. Each new group will receive clofarabine for the same number of days, if no intolerable side effects were seen. The number of days may be reduced to 3. The clofarabine dose per day is the same from group to group.
All participants will receive the same dose level of decitabine, idarubicin and cytarabine.
研究设计
- 研究类型
- Interventional
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Sign an IRB-approved informed consent document.
- •Age >/= 18 years and <65 years.
- •Diagnosis of AML [other than acute promyelocytic leukemia] with refractory/relapsed disease (Patients must be primary refractory, in relapse 1, or in relapse 2). NOTE: Patients with AML arising from prior MDS or MPN would be eligible even if they have not received treatment for the AML. NOTE: Patients with relapsed/refractory ALL would also be eligible for the phase II part of the study. NOTE: Use of hydroxyurea and/or up to 4 doses of cytarabine, for emergent cytoreduction is allowed
- •ECOG performance status of </=2 at study entry.
- •Organ function as defined below (unless due to leukemia):Serum creatinine </= 3 mg/dL;Total bilirubin </= 2.5 mg/dL; ALT (SGPT) </= 3 x ULN or </= 5 x ULN if related to disease
- •Cardiac ejection fraction ≥ 40% (by either cardiac ECHO or MUGA scan)
- •Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days. Men must agree not to father a child and agree to use a condom if his partner is of child bearing potential.
排除标准
- •Breast feeding women
- •Patients with uncontrolled active infections (viral, bacterial, and fungal are not eligible).
- •Patients with active secondary malignancy will not be eligible unless approved by the PI.
- •NOTE: Prior therapy with decitabine, clofarabine, idarubicin, or cytarabine is allowed, unless the prior therapy is identical to the schema/schedule proposed in this study
研究组 & 干预措施
Clofarabine + Cytarabine + Decitabine + Idarubicin
Phase I - Decitabine 20 mg/m2 by vein over approximately 1 hour daily for 5 days (days 1-5) Idarubicin 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 6-8) Cytarabine 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 6-10)
Phase II - Clofarabine 15 mg/m2 by vein over approximately 1 hour daily (number of days selected based on Phase I portion).
Decitabine 20 mg/m2 by vein over approximately 1 hour daily for 5 days (days 1-5) Idarubicin 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 6-8) Cytarabine 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 6-10)
干预措施: Decitabine (Drug)
Clofarabine + Cytarabine + Decitabine + Idarubicin
Phase I - Decitabine 20 mg/m2 by vein over approximately 1 hour daily for 5 days (days 1-5) Idarubicin 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 6-8) Cytarabine 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 6-10)
Phase II - Clofarabine 15 mg/m2 by vein over approximately 1 hour daily (number of days selected based on Phase I portion).
Decitabine 20 mg/m2 by vein over approximately 1 hour daily for 5 days (days 1-5) Idarubicin 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 6-8) Cytarabine 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 6-10)
干预措施: Idarubicin (Drug)
Clofarabine + Cytarabine + Decitabine + Idarubicin
Phase I - Decitabine 20 mg/m2 by vein over approximately 1 hour daily for 5 days (days 1-5) Idarubicin 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 6-8) Cytarabine 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 6-10)
Phase II - Clofarabine 15 mg/m2 by vein over approximately 1 hour daily (number of days selected based on Phase I portion).
Decitabine 20 mg/m2 by vein over approximately 1 hour daily for 5 days (days 1-5) Idarubicin 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 6-8) Cytarabine 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 6-10)
干预措施: Cytarabine (Drug)
Clofarabine + Cytarabine + Decitabine + Idarubicin
Phase I - Decitabine 20 mg/m2 by vein over approximately 1 hour daily for 5 days (days 1-5) Idarubicin 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 6-8) Cytarabine 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 6-10)
Phase II - Clofarabine 15 mg/m2 by vein over approximately 1 hour daily (number of days selected based on Phase I portion).
Decitabine 20 mg/m2 by vein over approximately 1 hour daily for 5 days (days 1-5) Idarubicin 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 6-8) Cytarabine 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 6-10)
干预措施: Clofarabine (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Clofarabine
时间窗: After second, 33 day cycle
Maximum tolerated dose (MTD) defined as the highest dose schedule in which 6 patients were treated with at most 1 experiencing a dose-limiting toxicity (DLT). Clofarabine 15 mg/m2 IV over approximately 1 hour daily (number of days selected based on Phase I portion).
Number of Participants With a Response
时间窗: 56 days
Primary endpoint is overall response defined as the best response either complete response, complete remission without platelet recovery, or complete remission without incomplete blood count recovery within 56 days.
次要结局
- To Determine the Disease-free Survival (DFS).(Up to 2 years after participants off study date)
- Overall Survival(Up to 2 years after participants off study date)