Reduced-Intensity Conditioning for Children and Adults With Hemophagocytic Syndromes or Selected Primary Immune Deficiencies (RICHI) (BMT CTN #1204)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 47
- 试验地点
- 43
- 主要终点
- Percentage of Participants With Overall Survival (OS)
研究概览
简要总结
HLH, HLH-related disorders, Chronic Granulomatous (CGD), HIGM1, Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX) and severe LAD-I represent primary immune disorders that are typically fatal without Hematopoietic Cell Transplant (HCT). However, transplant is often complicated by inflammation, infection and other co-morbidities. In addition, these disorders have been shown to be cured with partial chimerism, making them an ideal target for the use of reduced intensity approaches, where a portion of patients may not achieve full donor chimerism, but instead achieve stable mixed chimerism. Reduced-intensity conditioning strategies have demonstrated improved survival with decreased Treatment Related Mortality (TRM) in institutional series for patients with HLH (Cooper et al., 2006; Marsh et al., 2010; Marsh et al., 2011). However, graft loss and unstable chimerism remain challenges. An institutional case series from Cincinnati Children's Hospital demonstrated full or high-level chimerism and improved durable engraftment using intermediate (Day -14) timing alemtuzumab (Marsh et al., 2013b). This study aims to test the efficacy of the Intermediate RIC strategy in a prospective multi-center study including HLH as well as other primary immunodeficiencies where allogeneic transplant with RIC has been shown to be feasible and stable chimerism is curative.
详细描述
The primary goal of this Phase II clinical trial is to determine the one-year overall survival of patients treated for immune deficiencies including HLH, HLH-like disorders, CGD, HIGM1, IPEX syndrome, and severe LAD-I with Matched Related Donor (MRD)/ Matched Unrelated Donor (MUD) bone marrow transplant using a reduced-intensity conditioning strategy including intermediate-timing of alemtuzumab. The donor choice is an unaffected related bone marrow donor who is a 6/6 match at HLA-A, -B (intermediate or higher resolution) and -DRB1 (at high resolution using DNA-based typing) OR a 7/8 or 8/8 match for human leukocyte antigen (HLA)-A, -B, -C and -DRB1 (at high resolution using DNA-based typing), OR an unrelated bone marrow donor who is a 7/8 or 8/8 match at HLA-A, -B, -C and -DRB1 (at high resolution using DNA-based typing). The transplant conditioning regimen will include fludarabine, melphalan, and alemtuzumab starting at Day -14 (Flu/Mel/Alem). Graft Versus Host Disease (GVHD) prophylaxis will consist of cyclosporine and corticosteroids through engraftment. Post-transplant supportive care will include infection surveillance and prophylaxis, and disease-specific supportive care.
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
- 4 Months 至 45 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Hematopoietic stem cell transplant within 6 months of enrollment.
- •Uncontrolled bacterial, viral or fungal infection (currently receiving appropriate antimicrobials and experiencing progression or no clinical improvement) at time of enrollment. We recognize that patients with CAEBV may have ongoing EBV viremia at the time of initiating transplant therapy, but other patients should have no uncontrolled bacterial, viral or fungal infections at the time of enrollment (or prior to initiating the preparative regimen).
- •Pregnant or breastfeeding.
- •Seropositive for human immunodeficiency virus (HIV).
- •Alemtuzumab within 2 weeks of enrollment.
- •History of prior or current malignancy, especially malignancies with a likelihood of relapse and progression, with the exception of (1) EBV-associated lymphomas related to immune deficiency or lymphomas associated with X-linked LPD in a good remission, as they are unlikely to relapse after treatment; (2) Resected basal cell carcinoma or treated cervical carcinoma in situ. Cancer treated with curative intent will not be allowed unless approved by the Protocol Officer or one of the Protocol Chairs.
结局指标
主要结局
Percentage of Participants With Overall Survival (OS)
时间窗: 1 year and 18 months post-transplant
Overall survival is defined as survival of death from any cause.
次要结局
- Percentage of Participants With Overall Survival (OS) by Disease Type(1 year and 18 months post-transplant)
- Percentage of HLH Participants With HLH Reactivation Post-Transplant(1 year post-transplant)
- Percentage of Participants With Chronic GVHD(1 year post-transplant)
- Percentage of Participants With Neutrophil Engraftment(Day 42 post-transplant)
- Percentage of Participants Alive With Sustained Engraftment(1 year post-transplant)
- Percentage of Participants With Platelet Engraftment(Day 100 post-transplant)
- Percentage of Participants Alive With Sustained Engraftment by Disease Type(1 year post-transplant)
- Number of Participants With Acute Graft-Versus-Host Disease (GVHD)(1 year post-transplant)
- Percentage of Participants With Grade II-IV and Grade III-IV Acute GVHD(Day 100 and 6 months post-transplant)
- Number of Participants With Chronic GVHD(1 year post-transplant)