Safety and Efficacy of an Immunoablative Nonmyeloablative Conditioning Protocol for Autologous Bone Marrow Transplantation in Patients With Multiple Sclerosis
试验速览
- 阶段
- 不适用
- 入组人数
- 20
- 主要终点
- Engraftment parameters of Neutrophils and Platelets
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of an immunoablative nonmyeloablative conditioning protocol for autologous bone marrow transplantation in patients with Multiple Sclerosis. Patients meeting inclusion and exclusion criteria will start an immunoablative nonmyeloablative conditioning regimen followed by autologous bone marrow transplantation. Patients will be followed for one year by a neurologist to evaluate the course of the disease after treatment.
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
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Consenting patients fulfilling the Poser's clinical criteria for definite MS
- •Age: 18-65, males and females
- •Relapsing and secondary progressive forms of MS with evidence of significant activity of MS (clinical and on the MRI).
- •EDSS score of 2.0 to 7.0 (see table 1).
- •Failure to at least one line of the currently available treatment, registered treatments (i.e. interferons, Copaxone, Tysabri, Gilenya, Tecfidera, immunosuppression) for MS. The lack of response to these treatments will be determined/defined by either an increase (deterioration) of one degree (or more) in the EDSS score, when baseline EDSS is less than 5.0 or 0.5 degree, when baseline EDSS is 5.0 or more, during the last year or the appearance of one major relapse of MS during the same period of time (under treatment), or evidence for new activity of MS (new T2 lesions or gadolinium enhancing lesions) during the last 12 months.
- •Duration of disease: >2 years, except cases with rapid progression, i.e. annual relapse rate ≥2 per 2 years on a conventional treatment or malignant multiple sclerosis with very intense symptoms (types is in most cases deadly).
排除标准
- •Patients suffering from significant cardiac, renal or hepatic failure or any other disease that may risk the patient or interfere with the ability to undergo high dose immunosuppression associated toxicities (according to the existing limitations for autologous transplantation).
- •Patients with active infections.
- •Patients with severe cognitive decline or inability to understand and sign the informed consent.
- •Patients who were treated with investigational protocols during the last 3 months prior to the inclusion.
- •Patients who received high dose immunosuppression with autologous stem cell rescue in the past with no effect.
研究组 & 干预措施
Experimental
Fludarabine 30mg/m2 for 4 days, Cyclophosphamide 50mg/kg for 2 days, Alemtuzumab administered subcutaneously 24mg total dose.
Autologous bone marrow transplantation
干预措施: Autologous bone marrow transplantation (Procedure)
Experimental
Fludarabine 30mg/m2 for 4 days, Cyclophosphamide 50mg/kg for 2 days, Alemtuzumab administered subcutaneously 24mg total dose.
Autologous bone marrow transplantation
干预措施: Fludarabine (Drug)
Experimental
Fludarabine 30mg/m2 for 4 days, Cyclophosphamide 50mg/kg for 2 days, Alemtuzumab administered subcutaneously 24mg total dose.
Autologous bone marrow transplantation
干预措施: Cyclophosphamide (Drug)
Experimental
Fludarabine 30mg/m2 for 4 days, Cyclophosphamide 50mg/kg for 2 days, Alemtuzumab administered subcutaneously 24mg total dose.
Autologous bone marrow transplantation
干预措施: Alemtuzumab (Drug)
结局指标
主要结局
Engraftment parameters of Neutrophils and Platelets
时间窗: 1 year
Absolute Neutrophil count \>500 /microliter, Platelets\>20,000/microliter
Transplant related mortality by Day 100
时间窗: Day 100
次要结局
- Changes in the Expanded Disability Status Scale (EDSS score, as compared to baseline)(1 year)
- Overall survival (OS) at 1 year(1 year)
- Progression-free survival (PFS) at 1 year(1 year)
- Changes in MRI activity(1 year)