Treatment of Severe (Types II and III) Osteogenesis Imperfecta by Allogeneic Bone Marrow Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- To investigate the safety and toxicity of allogeneic bone marrow transplantation (BMT) in children with severe Osteogenesis Imperfecta (OI)
研究概览
简要总结
This protocol was a prospective, Phase I study of allogeneic bone marrow transplantation (BMT) as the primary therapy for Osteogenesis Imperfecta Types II and III. Compatible sibling donors and unrelated donors were stratified and analyzed according to the type of donor. All patients with a sibling donor will received a chemotherapy conditioning regimen; a non-T cell depleted allogeneic marrow, and GVHD prophylaxis. All patients with an unrelated donor will receive a chemoradiotherapy conditioning regimen, a T-cell depleted allogeneic marrow, and GVHD prophylaxis. The primary objective of this study was to investigate the safety and toxicity of these BMT procedures in this particular population.
详细描述
The secondary objective of the protocol assessed the engraftment of donor mesenchymal cells and their ability to increase the synthesis of normal type I procollagen relative to the synthesis of mutated type I procollagen and to assess whether BMT improves the bone structure and the clinical condition of these patients with OI.
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
- 3 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient has diagnosis of OI Type II or III. Because there are no specific, defined clinical criteria consistently used to make this diagnosis, we provide the following clinical guidelines to assist in diagnosis. Any appropriate combinations of the following clinical findings will be acceptable.
- •Diagnosis of OI Type II
- •Antenatal ultrasonography (if performed for other indications) by established obstetric impressions including short femurs, a small thoracic cage and poorly mineralized bones. Analysis of collagen synthesized from cultured cells obtained from chorionic villus sampling (CVS) may establish the diagnosis; however, no CVS will be performed specifically for enrollment into this study.
- •Clinical examination including prematurity, low birth weight, characteristic facies (blue sclera, beaked nose, extremely soft calvarium), "frog-leg" hips, small thoracic cavity, fractures at birth or shortly thereafter, loose skin or lax joints that cannot be readily explained by other factors.
- •Radiographic evaluation demonstrating various aspects of the characteristic picture of telescoped femur, bowed tibias, beaded ribs, flattened vertebral bodies and virtual absence of calvarial mineralization.
- •Diagnosis of OI Type III
- •Antenatal ultrasonography (performed for other indications) by established obstetric impressions for this more moderate form of OI. Chorionic villus sampling will be accepted as above.
- •Clinical examination including short stature, bony deformities, many fractures at birth or shortly thereafter. Blue scleras and dental abnormalities are also common.
- •Radiographic abnormalities including thin, osteopenic bones of the limbs with evidence of fractures, growth plate abnormalities, and an undermineralized calvarium.
- •Diagnosis of other diseases with possibly similar presentation to OI (e.g. hypophosphatasia and rickets) should be excluded by obtaining a serum calcium, phosphate and alkaline phosphatase. These parameters can be expected to be within normal limits (alkaline phosphatase may be somewhat elevated) in patients with OI.
- •Age less than 3 years at time of transplant.
- •Parents or legal guardians must sign an informed consent indicating that they are aware this is a research study and have been told of its possible benefits and toxic side effects, including treatment related mortality. Patients or their guardians will be given a copy of the consent form.
- •Identification of a suitable bone marrow donor.
- •Any donor must be of sufficient size so that adequate bone marrow may be harvested.
- •HLA mismatched sibling or unrelated donor. DNA typing will be per- formed on unrelated donors. Donors must be a 6/6 match or a 5/6 match (with serologic mismatch at a single Class I allele or mismatch at a single DR1 allele).
排除标准
- •Patients who are ventilatory dependent due to primary lung parenchymal disease prior to BMT.
- •Patients with evidence of basilar invagination/compression.
研究组 & 干预措施
2
干预措施: Irradiation, Total Body (Radiation)
2
干预措施: Cyclophosphamide (Drug)
2
干预措施: Mesenchymal Stem Cell Transplantation (Procedure)
2
干预措施: Busulfan (Drug)
2
干预措施: Bone Marrow Cell Transplantation (Other)
1
干预措施: Busulfan (Drug)
1
干预措施: Bone Marrow Cell Transplantation (Other)
1
干预措施: Cyclophosphamide (Drug)
1
干预措施: Cyclosporin (Drug)
1
干预措施: Mesenchymal Stem Cell Transplantation (Procedure)
结局指标
主要结局
To investigate the safety and toxicity of allogeneic bone marrow transplantation (BMT) in children with severe Osteogenesis Imperfecta (OI)
时间窗: 1 year
次要结局
未报告次要终点