Induction of Mixed Hematopoietic Chimerism in Patients With Severe Combined Immunodeficiency Disorders Using Allogeneic Bone Marrow and Post-Transplant Immunosuppression With Cyclosporine and Mycophenolate Mofetil
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Mixed hematopoietic chimerism in a population of pediatric patients with immunodeficiency diseases
研究概览
简要总结
This pilot clinical trial studies total-body irradiation followed by cyclosporine and mycophenolate mofetil in treating patients with severe combined immunodeficiency (SCID) undergoing donor bone marrow transplant. Giving total-body irradiation (TBI) before a donor bone marrow transplant using stem cells that closely match the patient's stem cells, helps stop the growth of abnormal cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may mix with the patient's immune cells and help destroy any remaining abnormal cells. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
详细描述
PRIMARY OBJECTIVES:
I. To safely establish partial lymphoid chimerism (1-95% donor cluster of differentiation [CD]3+ cells) using a non-lethal conditioning regimen in patients with severe combined immunodeficiency syndrome.
II. To define the kinetics of immune reconstitution following a non-lethal conditioning regimen in patients with immunodeficiency diseases.
OUTLINE:
Patients receive cyclosporine orally (PO) or intravenously (IV) on days -3 to 100 followed by a taper until day 180 and mycophenolate mofetil PO or IV on days 0-40 with a taper until day 96 in the absence of unacceptable toxicity. Unrelated donor recipients also undergo TBI on day 0. Patients undergo bone marrow transplant on day 0.
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 severe combined immunodeficiency syndrome:
- •SCID with presence of B lymphocytes
- •X-linked SCID (presence of B lymphocytes)
- •Autosomal recessive SCID
- •Patients with severe combined immunodeficiency syndrome:
- •SCID with absence of T and B lymphocytes
- •Patients with severe combined immunodeficiency syndrome:
- •Purine metabolite deficiencies, deficiencies of the purine metabolites
- •Adenosine deaminase (ADA) deficiency
- •Purine nucleoside phosphorylase (PNP) deficiency
- •DONOR: Related donor who is human leukocyte antigen (HLA) genotypically identical at least at one haplotype and may be genotypically or phenotypically identical for serological typing for HLA-A, B, C, and at the allele level for DRB1 and DQB1; related donors other than siblings must be matched at HLA-A, B, and C (at highest resolution available at the time of donor selection) and at DRB1 and DQB1 by deoxyribonucleic acid (DNA) typing; if more than one HLA-identical sibling is available, priority will be given to the oldest normal donor
- •DONOR: Unrelated donors who are prospectively matched for HLA-A, B, C, DRB1 and DQB1 by DNA typing at the highest resolution routinely available at the time of donor selection; only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing
排除标准
- •Patients with viral associated T cell immunodeficiency disorders, such as human immunodeficiency virus (HIV)
- •Patients with other disease or organ dysfunction that would limit survival to less than 30 days
- •DONOR: Identical twin
- •DONOR: Pregnancy
- •DONOR: HIV seropositive
- •DONOR: A positive anti-donor cytotoxic cross match is absolute donor exclusion
- •DONOR: Patient and donor pairs homozygous at a mismatched allele in the graft rejection vector are considered a two-HLA allele mismatch, i.e., the patient is A*0201, and this type of mismatch is not allowed
- •DONOR: < 6 months old, > 75 years old
研究组 & 干预措施
Treatment (cyclosporine, mycophenolate mofetil, transplant)
Patients receive cyclosporine PO or IV on days -3 to 100 followed by a taper until day 180 and mycophenolate mofetil PO or IV on days 0-40 with a taper until day 96 in the absence of unacceptable toxicity. Unrelated donor recipients also undergo TBI on day 0. Patients undergo bone marrow transplant on day 0.
干预措施: Allogeneic Bone Marrow Transplantation (Procedure)
Treatment (cyclosporine, mycophenolate mofetil, transplant)
Patients receive cyclosporine PO or IV on days -3 to 100 followed by a taper until day 180 and mycophenolate mofetil PO or IV on days 0-40 with a taper until day 96 in the absence of unacceptable toxicity. Unrelated donor recipients also undergo TBI on day 0. Patients undergo bone marrow transplant on day 0.
干预措施: Cyclosporine (Drug)
Treatment (cyclosporine, mycophenolate mofetil, transplant)
Patients receive cyclosporine PO or IV on days -3 to 100 followed by a taper until day 180 and mycophenolate mofetil PO or IV on days 0-40 with a taper until day 96 in the absence of unacceptable toxicity. Unrelated donor recipients also undergo TBI on day 0. Patients undergo bone marrow transplant on day 0.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (cyclosporine, mycophenolate mofetil, transplant)
Patients receive cyclosporine PO or IV on days -3 to 100 followed by a taper until day 180 and mycophenolate mofetil PO or IV on days 0-40 with a taper until day 96 in the absence of unacceptable toxicity. Unrelated donor recipients also undergo TBI on day 0. Patients undergo bone marrow transplant on day 0.
干预措施: Mycophenolate Mofetil (Drug)
Treatment (cyclosporine, mycophenolate mofetil, transplant)
Patients receive cyclosporine PO or IV on days -3 to 100 followed by a taper until day 180 and mycophenolate mofetil PO or IV on days 0-40 with a taper until day 96 in the absence of unacceptable toxicity. Unrelated donor recipients also undergo TBI on day 0. Patients undergo bone marrow transplant on day 0.
干预措施: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation (Procedure)
Treatment (cyclosporine, mycophenolate mofetil, transplant)
Patients receive cyclosporine PO or IV on days -3 to 100 followed by a taper until day 180 and mycophenolate mofetil PO or IV on days 0-40 with a taper until day 96 in the absence of unacceptable toxicity. Unrelated donor recipients also undergo TBI on day 0. Patients undergo bone marrow transplant on day 0.
干预措施: Total-Body Irradiation (Radiation)
结局指标
主要结局
Mixed hematopoietic chimerism in a population of pediatric patients with immunodeficiency diseases
时间窗: Up to 5 years
It will be established whether a non-lethal conditioning regimen can successfully induce mixed hematopoietic chimerism in a population of pediatric patients with immunodeficiency diseases, without adverse effects on mortality.
次要结局
未报告次要终点