CD45 and Alemtuzumab Monoclonal Antibody Conditioning Regimen For Allogeneic Donor Stem Cell Transplantation Of Patients With Severe Combined Immunodeficiency Disease (SCID) And Other Primary Immunodeficiency Disorders
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Number of Patients With Donor Engraftment
研究概览
简要总结
This study is to discover whether children with severe combined immunodeficiency disease (SCID) or other primary immunodeficiency disorder (PID) for which no satisfactory treatment other than stem cell transplantation (SCT) exists can be safely and effectively transplanted from HLA mismatched (up to one haplotype) related donors or unrelated matched or mismatched (up to one antigen) donors, when leukocytolytic monoclonal antibodies (MAb) and Fludarabine are the sole conditioning agents. Three monoclonal antibodies will be used in combination. Two of them are rat IgG1 (immunoglobulin G1) antibodies directed against two contiguous epitopes on the CD45 (common leucocyte) antigen. They have been safely administered as part of the conditioning regimen for 12 patients receiving allografts (HLA matched and mismatched) at this center. They produce a transient depletion of >90% circulating leucocytes. The third MAb is Campath 1H, a humanized rat anti-CD52 MAb. Campath 1H, Alemtuzumab, has been licensed to treat B-cell chronic lymphocytic leukemia (B-CLL) and more recently has been safely given at this and other centers as part of a sub-ablative conditioning regimen to patients with malignant disease. Because these MAb produce both profound immunosuppression and significant, though transient, myelodestruction we believe they may be useful as the sole conditioning regimen in patients with SCID, in whom the use of conventional chemotherapeutic agents for conditioning may produce or aggravate unacceptable and even lethal short term toxicity. We anticipate MAb mediated subablative conditioning will permit engraftment in a high percentage of these patients with little or no immediate or long term toxicity. Campath IH persists in vivo for several days after administration and so will be present over the transplant period to deplete donor T cells as partial GvHD prophylaxis. Additional Graft versus Host Disease (GvHD) prophylaxis may be provided by administration of FK506.
详细描述
Donor Stem Cell Processing for Mismatched Donors: Harvested peripheral blood stem cells will be enriched for CD34 cells using the CliniMACS CD34 Reagent system, according to Center for Cell and Gene Therapy (CAGT) SOPs.
Stem Cell Transplant Conditioning
Campath-1H will be given as 3 daily intravenous infusions and will be followed by Anti-CD45 which will be given as four daily intravenous infusions that will be completed two days prior to stem cell infusion. Diphenydramine will be administered i.v. q4h during the period of the course of the Campath and Anti-CD45 infusions.
Day
8 Campath 1H as per CAGT SOP Fludarabine 10 kg or less: 1 mg/kg; > 10 kg: 30 mg/m2
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
- •Patients with a diagnosis of: Severe combined immunodeficiency disease
- •This includes patients whose SCID is characterized by gene specific mutations as well as patients with clinically severe combined immunodeficiency without a defined genetic cause in which the diagnosis will be determined by a combination of clinical course with lymphocyte quantification and function assays.
- •Severe primary immunodeficiency disorder, including undefined T cell deficiency disorder, Wiskott-Aldrich syndrome, and other severe immunodeficiencies for which satisfactory conventional therapy does not exist.
- •Availability of an HLA mismatched (up to one haplotype) family member or an HLA matched or mismatched (up to one antigen) unrelated donor.
- •Creatinine < 2.5 x normal for age.
- •Life expectancy greater than 6 weeks
- •Lansky/Karnofsky greater than or equal to 70%
排除标准
- •Patients with an HLA matched related donor
- •Patients with symptomatic cardiac disease, or evidence of significant cardiac disease by echocardiogram (i.e., shortening fraction less than 25%)
- •Patients with known allergy to rat serum products
- •Patients with a severe infection that on evaluation by the Principal Investigator precludes ablative chemotherapy or successful transplantation
- •HIV positive
研究组 & 干预措施
Participants With SCID or Primary Immunodeficiency Disorder
all patient will receive an allogeneic transplant with the following conditioning regimen Campath -1H, Fludarabine, Anti-CD45
干预措施: Campath -1H (Biological)
Participants With SCID or Primary Immunodeficiency Disorder
all patient will receive an allogeneic transplant with the following conditioning regimen Campath -1H, Fludarabine, Anti-CD45
干预措施: Fludarabine (Drug)
Participants With SCID or Primary Immunodeficiency Disorder
all patient will receive an allogeneic transplant with the following conditioning regimen Campath -1H, Fludarabine, Anti-CD45
干预措施: Anti-CD45 (Biological)
Participants With SCID or Primary Immunodeficiency Disorder
all patient will receive an allogeneic transplant with the following conditioning regimen Campath -1H, Fludarabine, Anti-CD45
干预措施: Stem cell infusion (Procedure)
结局指标
主要结局
Number of Patients With Donor Engraftment
时间窗: 100 Days
次要结局
- Patients Alive at 1 Year(1 Year)
- Number of Patients With Grade III or IV Toxicity(100 days)
- Number of Patients With Grade III to IV Acute GVHD(100 days)
研究者
Robert Krance
Professor Pediatrics Hematology Oncology Center for Cell and Gene Therapy
Baylor College of Medicine