Hematopoietic Stem Cell Transplantation for Hurler Syndrome, Maroteaux Lamy Syndrome (MPS VI), and Alpha Mannosidase Deficiency (Mannosidosis)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Mean Percentage of Donor Cells in Study Population (Chimerism).
研究概览
简要总结
The purpose of this study is to determine the safety and engraftment of donor hematopoietic cells using this conditioning regimen in patients undergoing a hematopoietic (blood forming) cell transplant for Hurler syndrome, Maroteaux Lamy syndrome, Mannosidosis, or I-cell disease.
详细描述
Prior to transplantation, subjects will receive Busulfan intravenously (IV) via the Hickman line four times daily for 4 days, Cyclophosphamide intravenously via the Hickman line once a day for 4 days, and Anti-Thymocyte Globulin IV via the Hickman line twice daily for three days before the transplant. These three drugs are being given to subjects to help the new marrow "take" and grow.
On the day of transplantation, the donor's hematopoietic cells will be transfused via central venous catheter.
After hematopoietic cell transplant, subjects will then receive two drugs, cyclosporin and either methylprednisolone or Mycophenolate Mofetil (MMF). Cyclosporin and methylprednisolone or MMF are given to help prevent the complication of graft-versus-host disease and to decrease the chance that the new donor cells will be rejected.
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 Mucopolysaccharidosis, type I (e.g., Hurler syndrome), Maroteaux-Lamy syndrome (MPS VI), Alpha Mannosidosis, or mucolipidosis type II (I-cell disease) who have an HLA-identical or mismatched (at 1 antigen) related marrow, PBSC, or cord blood donor.
- •Patients with Mucopolysaccharidosis, type I, Maroteaux-Lamy syndrome (MPS VI), Alpha Mannosidosis, or mucolipidosis type II (I-cell disease) who have an HLA-identical or HLA-1 antigen mismatched unrelated marrow, PBSC, or HLA-0-2 antigen mismatched umbilical cord blood donor.
- •Patients with MPS type I, Maroteaux Lamy Syndrome (MPS VI), or mucolipidosis type II (I-cell disease) will have a mental developmental index within two standard deviations of the normal mean, as best as can be determined using Bayley scales of infant development or other standardized testing, recognizing that these may be affected by speech and/or hearing impairment.
- •Adequate organ function:
- •Cardiac: ejection fraction >40%; no decompensated congestive heart failure or uncontrolled arrhythmia
- •Renal: serum creatinine <2.0 mg/dl
- •Hepatic: total bilirubin <3x Upper limits of normal transaminases < 5.0 x Upper limits of normal
- •Signed consent.
排除标准
- •Presence of major organ dysfunction (see above)
- •Pregnancy
- •Evidence of HIV infection or known HIV positive serology
- •Patients or parents are psychologically incapable of undergoing BMT with associated strict isolation or documented history of medical non-compliance
- •Patients >50 kg may be at risk for having cell doses below the goal of ≥ 10 x 106 CD 34 cells/kg and therefore will not be eligible to receive unrelated PBSCs.
研究组 & 干预措施
Treatment Arm
All patients treated with chemotherapy and transplantation.
干预措施: Stem Cell Transplant (Procedure)
Treatment Arm
All patients treated with chemotherapy and transplantation.
干预措施: Busulfan, Cyclophosphamide, ATG (Drug)
结局指标
主要结局
Mean Percentage of Donor Cells in Study Population (Chimerism).
时间窗: at 21 days, 42 days, 60 days, 100 days, 6 months, and 1 year
Donor-derived engraftment determined by restriction fragment length polymorphism (RFLP).
次要结局
- Number of Patients Surviving on Study(at 100 days, 1 year, and 3 years post transplant)
- Number of Patients Who Failed Engraftment.(Day 42 Post Transplant)
- Number of Patients With Grade III-IV Acute Graft-versus-host Disease (aGVHD).(Day 100 Post Transplant)