A Non-Myeloablative Conditioning Regimen for Allogeneic Transplantation With Clofarabine, Cytarabine, and Thymoglobulin for Myelodysplastic Syndrome and Acute Myeloid Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Six-month Treatment Related Mortality
研究概览
简要总结
This study will test the combination of clofarabine, cytarabine, and thymoglobulin as a non-myeloablative conditioning regimen for patients with myelodysplastic syndromes or acute myeloid leukemia undergoing allogeneic stem cell transplant.
详细描述
Current reduced intensity conditioning regimens have been able to decrease TRM (treatment related mortality) but suffer from increased rates of disease relapse. Disease burden at transplantation, as measured by percent myeloblasts, predicts relapse. Current regimens employ fludarabine and busulfan with various adjutants, but these agents are not part of the usual armamentarium used versus leukemia and have questionable anti-leukemic activity. By substituting clofarabine and cytarabine, a combination with proven anti-leukemic activity in the relapsed and refractory setting as well as activity versus MDS, as the back bone of the regimen we hope overcome residual disease and improve post-transplant relapse rates. Furthermore the principal toxicity of this regimen is myelosuppression, which should be abrogated by the infusion of stem cells. Thymoglobulin is included due to its minimal contribution to toxicity but significant benefits in engraftment, and controlling acute and chronic GVHD, which are major contributors to TRM and disease specific activity in MDS.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Pregnant or nursing.
- •Active systemic infection considered opportunistic, life threatening or clinically significant at the time of treatment.
- •Severe concurrent disease, including severe insulin-dependent diabetes, uncontrolled hypertension, transient ischemic attacks, uncontrolled symptomatic coronary artery disease, or symptomatic CNS involvement or psychiatric illness/social situations that would limit compliance with study requirements.
- •Known HIV disease.
- •History of other malignancy except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast unless the subject has been off treatment and free from disease for > 3 years.
- •Active disease at the time of transplant.
研究组 & 干预措施
Arm 1: Non-myeloablative conditioning regimen
- Clofarabine 40mg/m2/day IV over two hours daily x 5 days on Days -6 thru -2
- Cytarabine 1gm/m2/day IV over two hours daily x 5 days on Days -6 thru -2 after the START of Clofarabine.
- Thymoglobulin 1.0mg/kg IV over 6 hours X 1 day on Day -4, then 2.5mg/kg/day x 2 days on Days -3 and -2.
- Stem Cell Transplant - On day 0 a minimum of total CD34+ cell dose of 2 x10E6/kg (actual weight of recipient) will be infused.
干预措施: Clofarabine (Drug)
Arm 1: Non-myeloablative conditioning regimen
- Clofarabine 40mg/m2/day IV over two hours daily x 5 days on Days -6 thru -2
- Cytarabine 1gm/m2/day IV over two hours daily x 5 days on Days -6 thru -2 after the START of Clofarabine.
- Thymoglobulin 1.0mg/kg IV over 6 hours X 1 day on Day -4, then 2.5mg/kg/day x 2 days on Days -3 and -2.
- Stem Cell Transplant - On day 0 a minimum of total CD34+ cell dose of 2 x10E6/kg (actual weight of recipient) will be infused.
干预措施: Cytarabine (Drug)
Arm 1: Non-myeloablative conditioning regimen
- Clofarabine 40mg/m2/day IV over two hours daily x 5 days on Days -6 thru -2
- Cytarabine 1gm/m2/day IV over two hours daily x 5 days on Days -6 thru -2 after the START of Clofarabine.
- Thymoglobulin 1.0mg/kg IV over 6 hours X 1 day on Day -4, then 2.5mg/kg/day x 2 days on Days -3 and -2.
- Stem Cell Transplant - On day 0 a minimum of total CD34+ cell dose of 2 x10E6/kg (actual weight of recipient) will be infused.
干预措施: Thymoglobulin (Drug)
Arm 1: Non-myeloablative conditioning regimen
- Clofarabine 40mg/m2/day IV over two hours daily x 5 days on Days -6 thru -2
- Cytarabine 1gm/m2/day IV over two hours daily x 5 days on Days -6 thru -2 after the START of Clofarabine.
- Thymoglobulin 1.0mg/kg IV over 6 hours X 1 day on Day -4, then 2.5mg/kg/day x 2 days on Days -3 and -2.
- Stem Cell Transplant - On day 0 a minimum of total CD34+ cell dose of 2 x10E6/kg (actual weight of recipient) will be infused.
干预措施: Stem cell infusion (Procedure)
结局指标
主要结局
Six-month Treatment Related Mortality
时间窗: 6 months
次要结局
- Disease Specific Response Rates(One, three, six and twelve months.)
- Rate of Acute Graft-versus-host Disease (GVHD)(Up to 100 days after transplant)
- Engraftment as Measured by Percent Donor Chimerism(Day +80-+90)
- Overall Survival(5 years from time of restaging)
- Rate of Chronic Graft-versus-host Disease (GVHD)(100 days-1 year after transplant)
- Disease-free Survival(5 years from time of restaging)
- Use Conventional STR-PCR Method for Monitoring Engraftment(Up to 1 year after transplant)
- Median Time to Progression(5 years from time of restaging)