Phase II Window Evaluation of the Farnesyl Transferase Inhibitor (R115777) Followed by 13-CIS Retinoic Acid, Cytosine Arabinoside and Fludarabine Plus Hematopoietic Stem Cell Transplantation in Children With Juvenile Myelomonocytic Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Response rate (CR or PR)
研究概览
简要总结
Giving chemotherapy drugs, such as R115777, isotretinoin, cytarabine, and fludarabine, before a donor bone marrow transplant or an umbilical cord transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. This phase II trial is studying how well giving combination chemotherapy together with donor bone marrow or umbilical cord blood transplant works in treating children with newly diagnosed juvenile myelomonocytic leukemia
详细描述
PRIMARY OBJECTIVES:
I. Determine the response rate of children with newly diagnosed juvenile myelomonocytic leukemia treated with R115777, isotretinoin, cytarabine, and fludarabine followed by allogeneic bone marrow or umbilical cord blood transplantation.
II. Determine the safety and toxicity of this regimen in these patients. III. Determine the tolerability of this regimen in these patients. IV. Determine the rate of 2-year event-free survival of patients treated with this regimen.
V. Determine whether prognostic subsets of these patients can be identified based on expression of clinical, genetic (NFI, monosomy 7, RAS gene), or hematopoietic characteristics.
OUTLINE: This is a multicenter study.
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
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Newly diagnosed, previously untreated juvenile myelomonocytic leukemia
- •Presenting with all of the following:
- •Absence of t(9;22) or bcr/abl by PCR
- •Absolute monocyte count greater than 1,000/mm^3
- •Less than 20% bone marrow blasts
- •Presenting with at least 2 of the following:
- •Elevated F hemoglobin
- •Myeloid precursors in peripheral blood
- •WBC greater than 10,000/mm^3
- •Sargramostim (GM-CSF) hypersensitivity
- •See Disease Characteristics
- •Bilirubin no greater than 2.0 mg/dL
- •ALT no greater than 3 times normal
- •Creatinine no greater than 2 times normal
- •No concurrent sargramostim (GM-CSF)
- •No concurrent proton pump inhibitors
排除标准
- 未提供
研究组 & 干预措施
Treatment (tipifarnib, bone marrow/umbilical cord transplant)
See detailed description.
干预措施: tipifarnib (Drug)
Treatment (tipifarnib, bone marrow/umbilical cord transplant)
See detailed description.
干预措施: isotretinoin (Drug)
Treatment (tipifarnib, bone marrow/umbilical cord transplant)
See detailed description.
干预措施: fludarabine phosphate (Drug)
Treatment (tipifarnib, bone marrow/umbilical cord transplant)
See detailed description.
干预措施: cytarabine (Drug)
Treatment (tipifarnib, bone marrow/umbilical cord transplant)
See detailed description.
干预措施: radiation therapy (Radiation)
Treatment (tipifarnib, bone marrow/umbilical cord transplant)
See detailed description.
干预措施: cyclophosphamide (Drug)
Treatment (tipifarnib, bone marrow/umbilical cord transplant)
See detailed description.
干预措施: anti-thymocyte globulin (Biological)
Treatment (tipifarnib, bone marrow/umbilical cord transplant)
See detailed description.
干预措施: allogeneic bone marrow transplantation (Procedure)
Treatment (tipifarnib, bone marrow/umbilical cord transplant)
See detailed description.
干预措施: double-unit umbilical cord blood transplantation (Procedure)
Treatment (tipifarnib, bone marrow/umbilical cord transplant)
See detailed description.
干预措施: umbilical cord blood transplantation (Procedure)
Treatment (tipifarnib, bone marrow/umbilical cord transplant)
See detailed description.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Response rate (CR or PR)
时间窗: Up to 6 years
The response rates in the up-front window with respect to whether or not patients had vas activating mutations will also be estimated by proportions.
Duration of response
时间窗: Up to 6 years
Will be estimated by Kaplan-Meier method.
Progression-free survival
时间窗: 2 years
Will be estimated by Kaplan-Meier method.
Evaluation of prognostic importance of genetic marker
时间窗: Up to 6 years
Logrank test and Cox proportional hazards model will be applied.
Grade 3 or greater toxicities assessed using CTC version 2.0
时间窗: Up to 6 years
次要结局
- Survival of patients receiving the window vs. not(Up to 6 years)
- Response status on end of course reports (pre vs.post)(Up to 6 years)