Low-Dose Total Body Irradiation and Fludarabine Followed By Unrelated Donor Stem Cell Transplantation for Patients With Fanconi Anemia - A Multicenter Trial
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 2
- 试验地点
- 5
- 主要终点
- Engraftment, defined as donor chimerism (mixed or complete)
研究概览
简要总结
Based on success in other diseases, the Fred Hutchinson Cancer Research Center (FHCRC) has developed a transplant procedure for Fanconi anemia (FA), which does not completely destroy the patient's remaining bone marrow. It should also be less harmful (toxic). Researchers wish to test whether this approach can overcome the graft failure often seen when bone marrow or peripheral blood stem cells from an unrelated donor are used. Researchers also will look at whether the procedure is less toxic than a conventional bone marrow transplant (BMT).
详细描述
PRIMARY OBJECTIVES:
I. To determine whether donor chimerism can be achieved in patients with Fanconi anemia receiving marrow or peripheral blood stem cell (PBSC) grafts from unrelated donors following low dose total body irradiation (TBI), fludarabine (fludarabine phosphate), mycophenolate mofetil, and cyclosporine.
II. To determine the lowest dose of TBI necessary to achieve donor chimerism in at least 80% of patients.
III. To determine the incidence of severe regimen-related toxicity.
SECONDARY OBJECTIVES:
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Any patient with marrow failure and increased chromosome fragility as determined in the diepoxybutane (DEB) or mitomycin C test
- •Any patient with Fanconi anemia (FA) with marrow failure meeting the following criteria:
- •Granulocyte count < 0.2 x 10^9/L
- •Platelet count < 20 x 10^9/L
- •Hemoglobin < 8 g/dl
- •Corrected reticulocyte count <1%
- •Any patient with FA as determined by DEB fragility, who has life-threatening marrow failure involving a single hematopoietic lineage
- •Any patient with FA and pre-existing cytogenetic abnormality including hematopoietic malignancy (myelodysplastic syndromes [MDS] or acute myeloid leukemia [AML]) in remission
- •DONOR: Unrelated Donors who are prospectively: Matched for human lymphocyte antigen (HLA)-DRB1 and DQB1 alleles (must be defined by high resolution typing); only a single allele disparity will be allowed for HLA -A, B, or C as defined by high resolution typing
- •DONOR: HLA typing will be performed at the highest level of resolution available at the time of transplant
排除标准
- •Evidence for hematopoietic malignancy in relapse
- •Heart or lung disease that would prevent compliance with conditioning and GvHD regimen or would severely limit the probability of survival
- •Human immunodeficiency virus (HIV) seropositive patients
- •Females who are pregnant or breastfeeding, or unwilling to use contraceptive techniques during and for the 12 months following treatment
- •DONOR: Donors who by DEB testing are found to have FA
- •DONOR: Donors who test positive in the lymphocytotoxic crossmatch assay
- •DONOR: Donors who are HIV positive
- •DONOR: Donors who for other medical or psychological reasons are not suitable as donors
研究组 & 干预措施
Treatment (allogeneic bone marrow or PBSC transplantation)
NON-MYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2, cyclosporine IV every 8-12 hours on days -3 to 0, and undergo low-dose TBI on day 0.
TRANSPLANTATION: Patients undergo allogeneic bone marrow or PBSC transplantation on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine PO or IV every 8-12 hours on days 1-100 with taper to day 177, and mycophenolate mofetil PO or IV every 8 hours on days 0-40 with taper to day 96.
干预措施: fludarabine phosphate (Drug)
Treatment (allogeneic bone marrow or PBSC transplantation)
NON-MYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2, cyclosporine IV every 8-12 hours on days -3 to 0, and undergo low-dose TBI on day 0.
TRANSPLANTATION: Patients undergo allogeneic bone marrow or PBSC transplantation on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine PO or IV every 8-12 hours on days 1-100 with taper to day 177, and mycophenolate mofetil PO or IV every 8 hours on days 0-40 with taper to day 96.
干预措施: cyclosporine (Drug)
Treatment (allogeneic bone marrow or PBSC transplantation)
NON-MYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2, cyclosporine IV every 8-12 hours on days -3 to 0, and undergo low-dose TBI on day 0.
TRANSPLANTATION: Patients undergo allogeneic bone marrow or PBSC transplantation on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine PO or IV every 8-12 hours on days 1-100 with taper to day 177, and mycophenolate mofetil PO or IV every 8 hours on days 0-40 with taper to day 96.
干预措施: total-body irradiation (Radiation)
Treatment (allogeneic bone marrow or PBSC transplantation)
NON-MYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2, cyclosporine IV every 8-12 hours on days -3 to 0, and undergo low-dose TBI on day 0.
TRANSPLANTATION: Patients undergo allogeneic bone marrow or PBSC transplantation on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine PO or IV every 8-12 hours on days 1-100 with taper to day 177, and mycophenolate mofetil PO or IV every 8 hours on days 0-40 with taper to day 96.
干预措施: allogeneic bone marrow transplantation (Procedure)
Treatment (allogeneic bone marrow or PBSC transplantation)
NON-MYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2, cyclosporine IV every 8-12 hours on days -3 to 0, and undergo low-dose TBI on day 0.
TRANSPLANTATION: Patients undergo allogeneic bone marrow or PBSC transplantation on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine PO or IV every 8-12 hours on days 1-100 with taper to day 177, and mycophenolate mofetil PO or IV every 8 hours on days 0-40 with taper to day 96.
干预措施: allogeneic hematopoietic stem cell transplantation (Procedure)
Treatment (allogeneic bone marrow or PBSC transplantation)
NON-MYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2, cyclosporine IV every 8-12 hours on days -3 to 0, and undergo low-dose TBI on day 0.
TRANSPLANTATION: Patients undergo allogeneic bone marrow or PBSC transplantation on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine PO or IV every 8-12 hours on days 1-100 with taper to day 177, and mycophenolate mofetil PO or IV every 8 hours on days 0-40 with taper to day 96.
干预措施: peripheral blood stem cell transplantation (Procedure)
Treatment (allogeneic bone marrow or PBSC transplantation)
NON-MYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2, cyclosporine IV every 8-12 hours on days -3 to 0, and undergo low-dose TBI on day 0.
TRANSPLANTATION: Patients undergo allogeneic bone marrow or PBSC transplantation on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine PO or IV every 8-12 hours on days 1-100 with taper to day 177, and mycophenolate mofetil PO or IV every 8 hours on days 0-40 with taper to day 96.
干预措施: mycophenolate mofetil (Drug)
结局指标
主要结局
Engraftment, defined as donor chimerism (mixed or complete)
时间窗: Day 180
Mixed chimerism is defined as presence of 5-95%, complete chimerism as \> 95% donor derived cells in the peripheral blood. Patient data will be summarized using standard statistical methods.
Acute GvHD defined using the Seattle criteria
时间窗: Day 84
For the evaluation of GvHD, time of onset, severity, and treatment will be recorded. Patient data will be summarized using standard statistical methods.
Regimen toxicity assessed using the Bearman scale
时间窗: Up to day 100
Patient data will be summarized using standard statistical methods.
次要结局
未报告次要终点