NCT04414046招募中2 期
Study of TCR Alpha Beta T-Cell and CD19 B-Cell Depletion for Hematopoietic Cell Transplantation From Haploidentical Donors in the Treatment of Primary Immunodeficiency and Inherited Metabolic Disorders in Children
适应症
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Incidence of successful donor engraftment
研究概览
简要总结
This research is being done to learn if a new type of haploidentical transplantation using TCR alpha beta and CD19 depleted stem cell graft from the donor is safe and effective to treat the patient's underlying condition. This study will use stem cells obtained via peripheral blood or bone marrow from parent or other half-matched family member donor. These will be processed through a special device called CliniMACS, which is considered investigational.
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
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient with any form of primary immune deficiency/dysregulatory disorders characterized by aberrant immune function, abnormal hematopoiesis, systemic or organ specific autoimmunity and/or non-malignant lymphoproliferation. This includes, but not limited to:
- •I. Disorders of phagocytes: Chronic granulomatous disease, Leukocyte adhesion deficiency, defects of IL-10 pathway, MonoMac syndrome
- •II. Defects of cellular and humoral immunity: Severe Combined Immunodeficiency Disorder (infants with classic SCID up to 2 years of age will be excluded due to other open protocol), X-linked hyper-IgM syndrome, DOCK8 deficiency, ZAP70 deficiency, common variable immunodeficiency (CVID), Wiskott-Aldrich syndrome, NEMO deficiency.
- •III. Disorder of immune dysregulation: Immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome, CTLA4 deficiency, LRBA deficiency, STAT1 GOF, STAT3 GOF, X-linked lymphoproliferative disease etc.
- •IV. Other PIDs and immune dysregulatory disorders who can be benefitted by HCT as deemed appropriate by the PI and the treating immunologist.
- •Histiocytic disorders including hemophagocytic lymphohistiocytosis (familial HLH (types 1-5), secondary HLH (refractory to therapy or with recurrent episodes of hyper inflammation) and multisystem refractory Langerhans cell histiocytosis.
- •Metabolic disorders that could improve or stabilize after stem cell transplantation such as mucopolysaccharidoses, neurodegenerative disorders, osteopetrosis, etc.
- •Inclusion Criteria:
- •Patient has a suitable genotypic identical match of 5/
- •The donor and recipient must be identical, as determined by high resolution typing, at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB
- •Patients must have adequate organ function measured by:
- •Cardiac: asymptomatic or if symptomatic then LVEF at rest must be ≥ 40% or SF ≥ 26%
- •Pulmonary: asymptomatic or if symptomatic DLCO ≥ 40% of predicted (corrected for hemoglobin) or pulse oximetry ≥ 92% on room air if the patient is unable to perform pulmonary function testing.
- •Renal: Creatinine clearance (CrCl) or glomerular filtration rate (GFR) must be > 50 mL/min/1.73 m
- •Hepatic: Serum conjugated (direct) bilirubin < 2.0 x ULN for age; AST and ALT < 5.0 x ULN for age.
- •Karnofsky or Lansky (age-dependent) performance score ≥ 50
- •Signed written informed consent
排除标准
- •Participants who have an HLA-matched sibling who is able and willing to donate bone marrow. Patients with a HLA-matched unrelated donors are not excluded.
- •Pregnant or breastfeeding females.
- •Patient has HIV or uncontrolled fungal, bacterial or viral infections.
- •Patient has received prior solid organ transplant.
- •Patient has active GVHD (> grade II) or chronic extensive GVHD due to a previous allograft at the time of inclusion.
研究组 & 干预措施
TCR alpha beta T cell depletion
Experimental
The leukapheresis product will undergo TCR alpha beta negative selection following a standardized protocol
干预措施: Haploidentical Hematopoietic Cell Transplantation (Biological)
结局指标
主要结局
Incidence of successful donor engraftment
时间窗: Day 100 after transplantation
The incidence of engraftment at day 100 will be described based on donor chimerism in the whole blood and or fractions sorted for T-cell and myeloid subsets. The donor chimerism will be scored as autologous reconstitution (\< 5% donor), mixed chimerism (5-49%=low mixed, 50-95%=high mixed), \> 95%=full donor chimerism.
次要结局
- Overall survival and Event-free survival(Up to 2 years post transplant)
- Acute grade II-IV GvHD(Up to 2 years post transplant)
- Chronic GvHD(Up to 2 years post transplant)
- Kinetics of platelet engraftment(Up to 42 days post transplant)
- Primary graft failure(Up to 2 years post transplant)
- Transplant-related complications(Up to 2 years post transplant)
- Transplant-related mortality(Up to 100 days post transplant)
- Cellular and Immunological reconstitution by laboratory evaluations(Up to 2 years post transplant)
- Kinetics of neutrophil engraftment(Up to 42 days post transplant)
- Secondary graft failure(Up to 2 years post transplant)
- Transplant-related infections(Up to 2 years post transplant)
研究者
研究点 (1)
Loading locations...
相似试验
招募中
2 期
TCR Alpha Beta T-cell Depleted Haploidentical HCT in the Treatment of Non-Malignant Hematological Disorders in ChildrenHemoglobinopathy (Disorder)Bone Marrow Failure SyndromeSevere Aplastic AnemiaNCT04356469Johns Hopkins All Children's Hospital17
招募中
2 期
Blinatumomab After TCR Alpha Beta/CD19 Depleted HCTB-cell Acute Lymphoblastic LeukemiaB-cell Childhood Acute Lymphoblastic LeukemiaB-Cell ALL, ChildhoodNCT04746209Medical College of Wisconsin25
终止
2 期
TCR Alpha Beta T-cell and CD19 B-cell Depleted Peripheral Blood Stem Cell Transplantation Using the CliniMACS System for Patients With Non-Malignant Hematologic Disorders From Matched or Mismatched, Related or Unrelated DonorsNon-Malignant Hematologic DisordersNCT03615144Memorial Sloan Kettering Cancer Center1
招募中
不适用
αβT Cell/CD19+ B Cell Depletion for Alternative Donor Allogeneic Hematopoietic Cell Transplantation (HSCT)Hematopoietic Stem Cell TransplantationHematologic MalignancyNCT06082947Nationwide Children's Hospital50
招募中
2 期
Alpha/Beta T Cell and CD19+ B Cell Depletion in Allogeneic Stem Cell Transplantation in Patients With Malignant DiseasesJuvenile Myelomonocytic LeukemiaMyelodysplastic SyndromesChronic Myeloid LeukemiaLymphoma, Non-HodgkinLymphoma, HodgkinAcute Myeloid LeukemiaAcute Lymphoblastic LeukemiaNCT05800210University of Florida20