Phase II Study for Patients With Primary Immunodeficiencies Using and Cd19+ Depleted Unrelated Donor or Partially Matched Related Donor Peripheral Stem Cells
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Event free survival
研究概览
简要总结
This is a Phase II trial to determine the ability of a reduced intensity conditioning regimen to allow successful engraftment with alpha/beta T and CD19+ depleted peripheral stem cell grafts from unrelated or partially matched related donors. There are two conditioning regimens depending upon patient diagnosis and age.
详细描述
This is a Phase II trial to determine the ability of a reduced intensity conditioning regimen to allow successful engraftment with alpha/beta T and CD19+ depleted peripheral stem cell grafts from unrelated or partially matched related donors. There are two conditioning regimens depending upon patient diagnosis and age.
The study will include patients 0-25 years with PID, including immune dysregulation syndromes for which hematopoietic stem cell transplant is indicated.
Treatment: Either conditioning regimen (listed below) followed by alpha/beta T and CD19+ depleted donor peripheral stem cells
- Reduced intensity conditioning with busulfan x 8 doses, fludarabine 40 mg/m2 x 4, thiotepa 5 mg/kg x 2, anti-thymocyte globulin (ATG) 3 mg/kg x 3.
OR 2. Myeloablative regimen with busulfan x 16 doses or Daily for four days, fludarabine 30 mg/m2 x 5, thiotepa 5 mg/kg x 2, ATG 3 mg/kg x 2.
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 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ages 0-25 years at time of enrollment
- •Immunodeficiencies for which allogeneic hematopoietic stem cell transplant is indicated, including severe combined immunodeficiencies, immunodeficiency polyendocrinopathy X-linked syndrome (IPEX), X-linked lymphoproliferative disease, chronic granulomatous disease, Wiskott-Aldrich syndrome (WAS), hyperIgM, and other life-threatening immunodeficiencies.
- •Immune dysregulation syndromes, including refractory or recurrent hemophagocytic lymphohistiocytosis, hemophagocytic lymphohistiocytosis (HLH) with genetic mutations, refractory multisystemic Langerhans cell histiocytosis, other macrophage activating syndrome (MAS) refractory to standard therapy.
- •Clinical status
- •Lansky or Karnofsky performance >=60
- •Organ Function:
- •Serum creatinine <1.5 x upper limit of normal for age Hepatic: ALT <=250; AST <=350
- •Cardiac shortening fraction >=27%
- •Bilirubin <2.5x normal (unless elevation due to Gilberts disease).
- •No active untreated infection
- •Signed informed consent
- •No HLA matched related donor available.
- •Females of childbearing potential must have negative pregnancy test.
排除标准
- •Uncontrolled bacterial, viral or fungal infections
- •HLA matched related or unrelated donor able to donate mobilized peripheral stem cells.
- •Pregnant Females
- •Matched related donor available for bone marrow donation
- •Donors Selection Criteria:
- •Donor selection will comply with 21 CFR 1271
- •Unrelated donor matched or up to one antigen mismatch as per National Marrow Donor Program (NMDP).
- •Haploidentical parent or sibling able to undergo mobilization for peripheral stem cell collection. Maternal donor preferred over paternal donor if both equally haploidentical.
- •Children's Hospital of Philadelphia (CHOP) Blood and Marrow Transplant (BMT) procedures apply for determining donor eligibility, including donor screening and testing for relevant communicable disease agents and diseases.
- •Unrelated donor identified through the National Marrow Donor Program (NMDP) and fulfills the NMDP criteria for donation. Unrelated donor willing and able to undergo mobilization of peripheral stem cells and apheresis
结局指标
主要结局
Event free survival
时间窗: One year
Event free survival in greater than 20 percent donor cells at one year for patients with primary immunodeficiencies (PID) who receive unrelated or partially matched related donor peripheral stem cell grafts which have been alpha/beta T depleted and CD19 depleted
Stable engraftment
时间窗: One year
Stable engraftment in greater than 20 percent donor cells at one year for patients with primary immunodeficiencies (PID) who receive unrelated or partially matched related donor peripheral stem cell grafts which have been alpha/beta T depleted and CD19 depleted
次要结局
- Severity of graft vs. host disease (GVHD)(One and two years)
- Incidence of graft vs. host disease (GVHD)(One and two years)
研究者
Timothy Olson
Medical Director, Hematopoietic Stem Cell Transplantation (HSCT) Program
Children's Hospital of Philadelphia