A Phase I/II Non-Myeloablative Allogeneic Hematopoietic Stem Cell Transplant for the Treatment of Patients With Hematologic Malignancies Using Busulfan, Fludarabine and Total Body Irradiation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 147
- 试验地点
- 1
- 主要终点
- Regimen-Related Toxicities
研究概览
简要总结
RATIONALE: Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
PURPOSE: This phase I/II trial is studying the side effects of giving busulfan and fludarabine together with total-body irradiation and to see how well they work in treating patients who are undergoing a donor stem cell transplant for hematologic cancer.
详细描述
OBJECTIVES:
Primary
- To assess safety and toxicity of the addition of busulfan added to an established fludarabine and low-dose total-body irradiation (TBI) conditioning regimen for non-myeloablative allogeneic transplantation in patients with hematologic malignancies. (Phase I)
- To assess the non-relapse mortality 1-year after conditioning with busulfan and fludarabine/TBI in patients with hematologic malignancies at moderate to high risk for graft rejection and/or relapse of underlying disease. (Phase II)
Secondary
- To assess overall survival 1-year survival. (Phase II)
- To assess the incidence of graft rejection. (Phase II)
- To assess the incidence of grade II-IV acute graft-vs-host disease (GVHD) and chronic extensive GVHD. (Phase II)
- To assess rates of disease progression and/or relapse-related mortality. (Phase II)
- To determine non-hematologic grade III-IV organ specific toxicity. (Phase II)
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 80 Years（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
- 未提供
研究组 & 干预措施
Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI)
Busulfan 3.2 mg/kg IV on day -5 Fludarabine 30 mg/m2/day x 3 (total dose 90 mg/m2, day -4 to day -2 TBI 200 centigray (cGy) x 1, day 0
干预措施: therapeutic allogeneic lymphocytes (Biological)
Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI)
Busulfan 3.2 mg/kg IV on day -5 Fludarabine 30 mg/m2/day x 3 (total dose 90 mg/m2, day -4 to day -2 TBI 200 centigray (cGy) x 1, day 0
干预措施: busulfan (Drug)
Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI)
Busulfan 3.2 mg/kg IV on day -5 Fludarabine 30 mg/m2/day x 3 (total dose 90 mg/m2, day -4 to day -2 TBI 200 centigray (cGy) x 1, day 0
干预措施: cyclosporine (Drug)
Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI)
Busulfan 3.2 mg/kg IV on day -5 Fludarabine 30 mg/m2/day x 3 (total dose 90 mg/m2, day -4 to day -2 TBI 200 centigray (cGy) x 1, day 0
干预措施: fludarabine phosphate (Drug)
Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI)
Busulfan 3.2 mg/kg IV on day -5 Fludarabine 30 mg/m2/day x 3 (total dose 90 mg/m2, day -4 to day -2 TBI 200 centigray (cGy) x 1, day 0
干预措施: Granulocyte colony-stimulating factor (G-CSF) (Drug)
Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI)
Busulfan 3.2 mg/kg IV on day -5 Fludarabine 30 mg/m2/day x 3 (total dose 90 mg/m2, day -4 to day -2 TBI 200 centigray (cGy) x 1, day 0
干预措施: mycophenolate mofetil (Drug)
Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI)
Busulfan 3.2 mg/kg IV on day -5 Fludarabine 30 mg/m2/day x 3 (total dose 90 mg/m2, day -4 to day -2 TBI 200 centigray (cGy) x 1, day 0
干预措施: peripheral blood stem cell transplantation (Procedure)
Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI)
Busulfan 3.2 mg/kg IV on day -5 Fludarabine 30 mg/m2/day x 3 (total dose 90 mg/m2, day -4 to day -2 TBI 200 centigray (cGy) x 1, day 0
干预措施: Total Body Irradiation (TBI) (Radiation)
Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI)
Busulfan 3.2 mg/kg IV on day -5 Fludarabine 30 mg/m2/day x 3 (total dose 90 mg/m2, day -4 to day -2 TBI 200 centigray (cGy) x 1, day 0
干预措施: Phenytoin (Drug)
Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI)
Busulfan 3.2 mg/kg IV on day -5 Fludarabine 30 mg/m2/day x 3 (total dose 90 mg/m2, day -4 to day -2 TBI 200 centigray (cGy) x 1, day 0
干预措施: Methotrexate (Drug)
结局指标
主要结局
Regimen-Related Toxicities
时间窗: 5 years post-transplant
Non-hematologic toxicities and adverse experiences ≥ Grade 3 occurrences measured up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant. The following data represents the number of regimen-related, grade 3 and 4 toxicities that occurred in each category.
Non-relapse Mortality
时间窗: Two years post-transplant
Percent of subjects with non-relapse mortality two years after conditioning with busulfan with fludarabine/200 cGy TBI in patients with hematologic malignancies at moderate to high risk for graft rejection and/or relapse of underlying disease.
次要结局
- Overall Survival(Years 1, 2, 3 and 5)
- Progression-Free Survival(Years 1, 2, 3, and 5)
- Relapse Mortality(Years 1 and 2)
- Acute Graft-Versus-Host Disease (aGVHD) Outcome(Day 100, Month 6)
- Chronic Graft-Versus-Host Disease (cGVHD) Outcome(Years 1, 2 and 3)
研究者
Richard Maziarz
Principal Investigator
OHSU Knight Cancer Institute