Phase II Trial of Gleevec and Low-Dose Ara-C for Elderly Patients With C-Kit Positive Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndromes
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Efficacy of a combination of imatinib and low dose ara-C in elderly or high-risk patients with AML and MDS, as measured by the rate of early mortality or progression.
研究概览
简要总结
The goal of this clinical research study is to learn if the combination of Gleevec (imatinib mesylate) and low doses of Cytarabine (ara-C) may help to control leukemia while causing fewer side effects than standard high dose chemotherapy.
详细描述
Imatinib mesylate is a drug that blocks a certain protein. This protein is thought to be important in the growth of leukemia cells. Ara-C is a chemotherapy drug that has been used for many years to treat AML and MDS.
Imatinib mesylate (Gleevec) is a protein-tyrosine kinase inhibitor that inhibits the Bcr-Abl tyrosine kinase, as well as the receptor tyrosine kinases for platelet- derived growth factor (PDGF) and stem cell factor (SCF), c-Kit, and inhibits PDGF- and SCF-mediated cellular events. c-Kit is expressed in over 90% of patients with AML.
The treatment of AML for patients age 65 or older with AML or high-risk MDS (age ³ 60 if high-risk cytogenetics) have a poor prognosis with induction chemotherapy. Response rate is no more than 45% with an induction mortality of at least 25%, and 1-year survival no better than 20%. Indeed, most patients in these age groups are not even offered therapy and are managed with supportive care only. Thus, new therapies that are better tolerated are needed.
Imatinib alone can induce response in nearly 20% of patients, and there is synergy with low concentrations of ara-C. In this study we plan to investigate the combination of imatinib and low-dose ara-C.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients who are not candidates for intensive chemotherapy with any of the following diagnosis:
- •AML or MDS (with >/=5% blasts) age >/= 65 years old (or age >/= 60 if high-risk cytogenetics), or
- •AML or MDS (RAEB or RAEBT) of any cytogenetic group age 60 or older with minimally treated disease who have relapsed disease or are refractory to therapy and not likely to require cytoreductive therapy within one month, and, or
- •Patients with WHO performance status of 0 to 2
- •Patients must have recovered from prior cytotoxic chemotherapy; treatment with hydrea is allowed up to 24 hours prior to day 1 of study drug administration
- •Written informed consent obtained according to local guidelines
- •Patients must have a serum creatinine of </= 1.5 x ULN, SGPT </= 3 x ULN and total bilirubin </= 2.0 x ULN.
- •Patients with >/= 20% blasts positive for c-kit (CD117) (except for CMML)
- •Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients of childbearing potential must agree to employ an effective method of birth control throughout the study and for up to 3 months following discontinuation of study drug.
排除标准
- •Patients with uncontrolled active infection
- •Patients with NYHA class III or IV
- •Women who are pregnant
- •Women who are breast feeding
研究组 & 干预措施
Gleevec + Low-Dose Ara-C
干预措施: Gleevec (Drug)
Gleevec + Low-Dose Ara-C
干预措施: Ara-C (Drug)
结局指标
主要结局
Efficacy of a combination of imatinib and low dose ara-C in elderly or high-risk patients with AML and MDS, as measured by the rate of early mortality or progression.
时间窗: April 2007
次要结局
- Rate of overall response, including CRp and PR.(April 2007)
- To determine the safety profile of this combination.(April 2007)
- To determine the impact on long-term survival of this therapy.(April 2007)
- To determine the duration of responses obtained with this therapy.(April 2007)
- To determine the impact of this therapy in cognitive function.(April 2007)
- To determine the effect of this approach in quality of life of this patient population.(April 2007)
- To determine the overall costs (health economic analysis) associated with this combination therapy.(April 2007)