Busulfan, Cyclophosphamide, Imatinib Mesylate and Autologous Stem Cell Transplantation in Patients With Chronic Myelogenous Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Number of participants with CML alive in cytogenetic remission at one year following treatment
研究概览
简要总结
The goal of this clinical research is to learn if treatment with high-dose busulfan and cyclophosphamide plus autologous bone marrow transplantation followed by treatment with Gleevec (imatinib mesylate) is effective in treating chronic myelogenous leukemia (CML).
Objectives:
- To assess the efficacy of high dose busulfan-cyclophosphamide and autologous hematopoietic transplantation with post transplant Imatinib mesylate for the treatment of CML. The primary endpoint of the study is to determine the proportion of patients with CML alive in cytogenetic remission at one year following this treatment.
- Secondary endpoints are time to progression and survival.
详细描述
Busulfan and cyclophosphamide are chemotherapy drugs which were designed to kill leukemia cells. An autologous bone marrow transplant is given after treatment with busulfan and cyclophosphamide to help in the recovery of blood and immune cells after this treatment. Imatinib mesylate is a drug which helps to stop the growth of leukemia cells. It is given after the transplant to help kill any remaining leukemia cells.
Before treatment, you will have a complete physical exam. You will have approximately 4 tablespoons of blood drawn for tests to check on the status of the disease, to check organ functions, and to check for infectious diseases (hepatitis, HIV, etc.). You will have a sample of bone marrow collected. To collect a bone marrow sample, an area of the hip or chest bone is numbed with anaesthetic and a small amount of bone marrow is withdrawn through a large needle. All of these tests are being done to make sure you are eligible for this treatment. If you are found to have a "blast crisis," you will not be eligible to continue on this study.
If you are eligible or if it has not already been done recently, you will be taken to the operating room and have around 4-6 cups of bone marrow collected. The procedure will be performed under general anesthesia. The procedure is similar to the bone marrow collection at the start of the study, however, more bone marrow will be collected. The bone marrow that is collected will be frozen and stored to be given back to you after high dose chemotherapy. Before the procedure, you will be asked to donate blood (if possible). This blood will be given back to you after the procedure to replace the bone marrow that was collected. You may also need a blood transfusion from another donor.
For patients who cannot undergo the procedure of bone marrow harvesting or if not enough bone marrow was collected during the bone marrow harvesting procedure, stem cells may be collected from the blood. Normally, there are very few stem cells in the blood. Most of them are in the bone marrow. To help move or "mobilize" the cells needed from your bone marrow to your blood, you will be given injections under the skin once a day of a drug called G-CSF. The injections may given by a nurse in the hospital, in the outpatient setting, or you may learn how to give the injection yourself. Blood samples (1 tablespoon) will be drawn every day to see if there are enough stem cells in your blood. After 4-6 days of treatment with G-CSF, you will undergo a procedure called leukapheresis. This procedure is similar to donating blood to a blood bank. Blood is collected and run through a machine that processes the blood and separates the cells needed for transplantation, giving the rest back to you. The separated cells are frozen and stored to give back you after high dose chemotherapy. You may need up to 3 leukapheresis procedures to collect enough cells.
Patients who had adequate amounts of their bone marrow or blood stem cells harvested in the past will not need additional harvesting of stem cells.
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
- — 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Criteria for hematopoietic stem cell collection and cryopreservation: a- Patients with Philadelphia chromosome positive CML < age 70 who achieve a cytogenetic remission (no Ph+ cells on bone marrow cytogenetics, at least twenty metaphases counted) are eligible for hematopoietic stem cell collection and cryopreservation. b- Patients must have a Zubrod PS <
- •c.Creatinine < 1.8 mg/dl d.Serum bilirubin < 1.5 mg/dl e. SGPT < 3 x normal values f. Patients with an HLA identical sibling are eligible if they refuse allogeneic transplantation.
- •Patients are eligible for high dose therapy and autologous transplantation if they meet the following criteria (numbered 2-13): - Cytogenetic relapse characterized by > 10% Ph+ metaphases (by FISH analysis or > 2 of 20 Ph+ metaphases on 2 consecutive cytogenetic studies at least 1 month apart).
- •Cytogenetic relapse (as above) with hematologic remission or chronic phase disease, or
- •Accelerated phase or second or subsequent chronic phase.
- •Availability of stored autologous hematopoietic stem cells collected when the patient was in cytogenetic complete remission (0 of >= 20 metaphases positive for Ph+ cells).A minimum of 0.5 x 10 6 CD34 positive cells/kg or 1 x 10 8 total nucleated cells/Kg must be available.
- •Age < 70 years.
- •Zubrod PS <=
- •Creatinine < 1.8 mg/dL.
- •Cardiac ejection fraction > 40%.
- •DLCO > 50% of the predicted value.
- •Serum bilirubin < 1.5 mg/dL.
- •SGPT < 3 x normal values.
- •Patients with an HLA identical sibling are eligible if they refuse allogeneic transplantation.
排除标准
- •Uncontrolled life-threatening infections or comorbid condition that could impair tolerance to the regimen.
- •HIV positivity.
- •Pregnant or lactating women.
- •Blast crisis (>30% blasts in blood or marrow)
- •Hepatitis B or C positivity.
研究组 & 干预措施
Autologous Transplantation
Busulfan 130 mg/m^2 intravenous (IV) every 24 hours Days -7 to -4; Cyclophosphamide 60 mg/kg over 4 hours Day -3 and -2; Imatinib Mesylate Starting dose 100 mg/day, and Autologous Stem Cell Transplantation on Day 0.
干预措施: Busulfan (Drug)
Autologous Transplantation
Busulfan 130 mg/m^2 intravenous (IV) every 24 hours Days -7 to -4; Cyclophosphamide 60 mg/kg over 4 hours Day -3 and -2; Imatinib Mesylate Starting dose 100 mg/day, and Autologous Stem Cell Transplantation on Day 0.
干预措施: Cyclophosphamide (Drug)
Autologous Transplantation
Busulfan 130 mg/m^2 intravenous (IV) every 24 hours Days -7 to -4; Cyclophosphamide 60 mg/kg over 4 hours Day -3 and -2; Imatinib Mesylate Starting dose 100 mg/day, and Autologous Stem Cell Transplantation on Day 0.
干预措施: Imatinib Mesylate (Drug)
Autologous Transplantation
Busulfan 130 mg/m^2 intravenous (IV) every 24 hours Days -7 to -4; Cyclophosphamide 60 mg/kg over 4 hours Day -3 and -2; Imatinib Mesylate Starting dose 100 mg/day, and Autologous Stem Cell Transplantation on Day 0.
干预措施: Autologous Stem Cell Transplantation (Procedure)
结局指标
主要结局
Number of participants with CML alive in cytogenetic remission at one year following treatment
时间窗: Baseline to 1 Year post treatment, up to 18 months
Cytogenetic complete remission confirmed via bone marrow examination for morphology, cytogenetics or Fluorescence in situ hybridization (FISH).
次要结局
未报告次要终点