A Prospective Randomized Phase I/II Study of Clofarabine (Clo) and Ara-C vs Clo and Ida vs Clo Plus Ida and Ara-C in Patients With First Relapse or First Salvage of Primary Refractory AML; and High-Grade MDS(>/= 10% Blasts); or CML in Myeloid Blasts Phase as Front Line Therapy or in First Salvage.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 116
- 试验地点
- 1
- 主要终点
- Participants With a Response
研究概览
简要总结
The goal is to compare the drug combinations clofarabine/idarubicin/ara-C, clofarabine/ara-C, and clofarabine/idarubicin in the treatment of patients with Acute Myeloid Leukemia, high-grade MDS, or myeloid blast phase of Chronic Myeloid Leukemia who have relapsed following their initial therapy.
详细描述
Clofarabine is a new drug that was designed to help treat leukemia. Ara-C and idarubicin are drugs that are commonly used to help treat leukemia.
Before treatment starts, you will be asked questions about your medical history and have a complete physical exam. You will have blood samples (about 1 tablespoon) collected for routine lab tests. You will either have an echocardiogram or a multiple-gated acquisition (MUGA) scan to check on the function of your heart. You will have a sample of bone marrow collected to check on the status of the disease. To collect a bone marrow sample, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle. Women who are able to have children must have a negative blood or urine pregnancy test.
After each cycle of therapy, you will not receive the next cycle of chemotherapy until your blood counts have recovered and any possible side effects have gone away (for around 3 to 6 weeks). If the disease gets worse or side effects become too severe, treatment will stop. You must stay in Houston for the first 4 to 6 weeks (average) of treatment and are required to return to Houston to receive each additional cycle of chemotherapy (up to 6 days each cycle).
You will be assigned to receive treatment with clofarabine plus idarubicin and ara-C.
For participants in the clofarabine/idarubicin/ara-C group, the clofarabine will be given by vein over 1 hour once a day for 5 days in a row, on Days 2 to 6 of each cycle. Idarubicin will be given by vein over 30 minutes for 3 days in a row, on Days 1 to 3 of each cycle. Ara-C will be given by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle. Idarubicin is usually started around 1 hour after the completion of clofarabine, and ara-C about 4 hours after the start of the clofarabine infusion. This 6 day period is called a cycle of chemotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 59 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >/= 18 years and < 60 years.
- •Must be in first relapse of AML, or must receive treatment as first salvage in primary refractory AML; or have high-risk MDS (>/= 10% blasts) with not more than one prior regimen of chemotherapy (therapy with hematopoietic growth factors, biological or targeted therapies are not counted). Patients in CML myeloid blast phase may receive clofarabine as frontline therapy or in first salvage.
- •Total bilirubin </= 2mg/dL, Serum glutamic pyruvic transaminase (SGPT) </= 4 upper limit of normal (ULN), creatinine </= 2.0mg/dL.
- •Eastern Cooperative Oncology Group (ECOG) performance status </=
- •Signed informed consent.
- •Male and female patients who are fertile agree to use an effective barrier method of birth control (ie, latex condom, diaphragm, cervical cap, etc) to avoid pregnancy. Female patients need a negative serum or urine pregnancy test within 7 days of study enrollment (applies only if patient is of childbearing potential. Non-childbearing is defined as >= 1 year postmenopausal or surgically sterilized).
排除标准
- •Previous treatment with clofarabine.
- •Active, uncontrolled, systemic infection considered opportunistic, life threatening, or clinically significant at the time of treatment, or any severe, concurrent disease, which, in the judgment of the investigator and after discussion with the Principal Investigator, would make the patient inappropriate for study entry.
- •Symptomatic central nervous system (CNS) involvement.
- •Patients who receive other chemotherapy. Patients must have been off previous therapy of >/= 2 weeks and must have recovered from acute toxicity of all previous therapy prior to enrollment. Treatment may start earlier following discussion with the Principal Investigator.
- •Cardiac ejection fraction </= 30%.
研究组 & 干预措施
Clofarabine + Ara-C
Clofarabine 40 mg/m^2 by vein over 1 hour daily for 5 days.
Ara-C Starting dose: 1 g/m^2 by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle.
干预措施: Clofarabine 40mg/m^2 (Drug)
Clofarabine + Ara-C
Clofarabine 40 mg/m^2 by vein over 1 hour daily for 5 days.
Ara-C Starting dose: 1 g/m^2 by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle.
干预措施: Ara-C 1 g/m^2 (Drug)
Clofarabine + Idarubicin
Clofarabine 22.5 mg/m^2 by vein over 1 hour daily for 5 days.
Idarubicin 10 mg/m^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle.
干预措施: Idarubicin 10mg/m^2 (Drug)
Clofarabine + Idarubicin
Clofarabine 22.5 mg/m^2 by vein over 1 hour daily for 5 days.
Idarubicin 10 mg/m^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle.
干预措施: Clofarabine 22.5mg/m^2 (Drug)
Clofarabine + Idarubicin + Ara-C
Clofarabine 22.5 mg/m^2 by vein over 1 hour daily for 5 days.
Idarubicin 6 mg/m^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle.
Ara-C Starting dose: 0.75 g/m^2 by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle.
干预措施: Ara-C 0.75 g/m^2 (Drug)
Clofarabine + Idarubicin + Ara-C
Clofarabine 22.5 mg/m^2 by vein over 1 hour daily for 5 days.
Idarubicin 6 mg/m^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle.
Ara-C Starting dose: 0.75 g/m^2 by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle.
干预措施: Clofarabine 22.5mg/m^2 (Drug)
Clofarabine + Idarubicin + Ara-C
Clofarabine 22.5 mg/m^2 by vein over 1 hour daily for 5 days.
Idarubicin 6 mg/m^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle.
Ara-C Starting dose: 0.75 g/m^2 by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle.
干预措施: Idarubicin 6 mg/m^2 (Drug)
结局指标
主要结局
Participants With a Response
时间窗: Up to 6 years
Response assessed by blood test or bone marrow aspirate following day 21 of induction and then every 2 weeks thereafter until remission or non-response. Complete remission (CR): Disappearance all clinical and/or radiologic evidence of disease; Neutrophil count \> 1.0 x10\^9/L and platelet count \>100x10\^9/L, and normal bone marrow differential (\< 5% blasts). Complete remission without platelet recovery (CRp): Peripheral blood and bone marrow results as for CR, but with platelet counts of \> 20 x 10\^9/L and \< 100 x 10\^9/L. Partial remission (PR): Peripheral blood count recovery as for CR, but with decrease in marrow blasts of \> 50% and not more than 6-25% abnormal cells in the marrow. All other responses considered as failures.
次要结局
- Overall Response Rate (ORR)(Up to 6 years)