Autologous Hematopoietic Stem Cell Transplant for Neuromyelitis Optica Spectrum Disorder (NMOSD)
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- Progression-Free Survival
研究概览
简要总结
This study is designed to treat your disease with an autologous stem cell transplant using a regimen of immune suppressant drugs and chemotherapy to reset your immune system and to determine if your disease will go into long-term remission.
详细描述
The autologous stem cell transplant used in this research study is an investigational procedure that uses cyclophosphamide (chemotherapy), rabbit antithymocyte globulin (rATG) (a protein that kills the immune cells that are thought to be causing your disease), rituximab (a biologic drug that targets B cells of your immune system), and intravenous immunoglobulin (IVIg) (pooled IgG antibodies from plasma donors with immunomodulatory and anti-inflammatory effects), followed by return of your own previously collected blood stem cells (autologous stem cell transplant). One day of plasmapheresis will also be performed the day prior to admission for stem cell transplant to remove disease-causing antibodies. The ability of this experimental treatment to stop relapses and progression (worsening) of your NMOSD will be assessed.
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
- •Age 18 - 65 years old at the time of pre-transplant evaluation
- •An established diagnosis of NMOSD (with or without aquaporin 4 (AQP4)-IgG antibody)
排除标准
- •Under age of 18 or over age of 65
- •Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible, or any adult who is unable to consent (for adults cognitively impaired due to disease, consent may be obtained from the closest living relative).
- •Paraplegia or quadriplegia (must be able to use a walker if even for only a few feet)
- •Extensive subcortical white matter lesions
- •Uncontrolled diabetes mellitus or any other illness that in the opinion of the investigators would jeopardize the ability of the patient to tolerate aggressive treatment
- •Myocardial infarction within the last 12 months. If longer than 12 months, must pass a dobutamine stress test and be cleared by cardiology.
- •Active systemic lupus erythematous, Sjogren's, myasthenia gravis, or another autoimmune disease
- •Sickle cell disease, sickle cell disease, or coagulopathy
- •Prior history of malignancy that required any radiotherapy, chemotherapy, or biological therapy
- •Positive pregnancy test, inability or unable to pursue effective means of birth control, or failure to willingly accept or comprehend irreversible sterility as a side effect of therapy
- •Women who are breastfeeding
- •Untreated life-threatening cardiac arrhythmia on electrocardiogram (EKG) or 24-hour holter
- •Left ventricular ejection fraction (LVEF) <50%
- •Tiffeneau-Pinelli index (FEV1/FVC) <70% of predicted after bronchodilator therapy (if necessary), or diffusing capacity of lung for carbon monoxide (DLCO) hemoglobin corrected <70 % predicted
- •Serum creatinine >2.0 mg/dl
- •Liver cirrhosis, transaminases >2x of normal limits, or bilirubin >2.0 mg/dl unless due to Gilbert's disease
- •Major hematological abnormalities such as platelet count < 100,000/μl or absolute neutrophil count (ANC) < 1000/μl
- •Active infection except asymptomatic bacteriuria
- •Presence of metallic objects implanted in the body that would preclude the ability of the patient to safely have magnetic resonance imaging (MRI) exams
- •Known hypersensitivity to mouse, rabbit, or E. coli derived proteins
- •Human immunodeficiency virus (HIV) positive
- •Hepatitis B or C positive
- •Use of natalizumab (Tysabri) within the previous six months
- •Use of fingolimod (Gilenya) within the previous three months
- •Use of dimethyl fumarate (Tecfidera) within the previous three months
- •Use of teriflunomide (Aubagio) unless cleared from the body (plasma concentration <0.02mcg/ml) following elimination from the body with cholestyramine 8g three times a day for 11 days
- •Use of alemtuzumab (Lemtrada/Campath) within previous 12 months
- •Use of rituximab (Rituxan) or ocrelizumab (Ocrevus) within previous six months
- •Prior treatment with mitoxantrone (Novantrone)
研究组 & 干预措施
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cell Therapy will be performed as follows: Autologous stem cells will be infused after conditioning with rituximab, cyclophosphamide, mesna, rATG (rabbit), and methylprednisolone. Granulocyte-colony stimulating factor (G-CSF) and intravenous immunoglobulin (IVIg) will be administered post-transplant.
干预措施: Rituximab (Drug)
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cell Therapy will be performed as follows: Autologous stem cells will be infused after conditioning with rituximab, cyclophosphamide, mesna, rATG (rabbit), and methylprednisolone. Granulocyte-colony stimulating factor (G-CSF) and intravenous immunoglobulin (IVIg) will be administered post-transplant.
干预措施: Cyclophosphamide (Drug)
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cell Therapy will be performed as follows: Autologous stem cells will be infused after conditioning with rituximab, cyclophosphamide, mesna, rATG (rabbit), and methylprednisolone. Granulocyte-colony stimulating factor (G-CSF) and intravenous immunoglobulin (IVIg) will be administered post-transplant.
干预措施: Mesna (Drug)
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cell Therapy will be performed as follows: Autologous stem cells will be infused after conditioning with rituximab, cyclophosphamide, mesna, rATG (rabbit), and methylprednisolone. Granulocyte-colony stimulating factor (G-CSF) and intravenous immunoglobulin (IVIg) will be administered post-transplant.
干预措施: rATG (Drug)
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cell Therapy will be performed as follows: Autologous stem cells will be infused after conditioning with rituximab, cyclophosphamide, mesna, rATG (rabbit), and methylprednisolone. Granulocyte-colony stimulating factor (G-CSF) and intravenous immunoglobulin (IVIg) will be administered post-transplant.
干预措施: Methylprednisolone (Drug)
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cell Therapy will be performed as follows: Autologous stem cells will be infused after conditioning with rituximab, cyclophosphamide, mesna, rATG (rabbit), and methylprednisolone. Granulocyte-colony stimulating factor (G-CSF) and intravenous immunoglobulin (IVIg) will be administered post-transplant.
干预措施: G-CSF (Drug)
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cell Therapy will be performed as follows: Autologous stem cells will be infused after conditioning with rituximab, cyclophosphamide, mesna, rATG (rabbit), and methylprednisolone. Granulocyte-colony stimulating factor (G-CSF) and intravenous immunoglobulin (IVIg) will be administered post-transplant.
干预措施: IVIg (Biological)
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cell Therapy will be performed as follows: Autologous stem cells will be infused after conditioning with rituximab, cyclophosphamide, mesna, rATG (rabbit), and methylprednisolone. Granulocyte-colony stimulating factor (G-CSF) and intravenous immunoglobulin (IVIg) will be administered post-transplant.
干预措施: Autologous Stem Cells (Biological)
结局指标
主要结局
Progression-Free Survival
时间窗: 5 years
Disease progression defined as: 1.0-point increase in the Expanded Disability Status Scale (EDSS) on consecutive evaluations at least six months apart and not due to a non-NMO disease process. The EDSS scale ranges from 0 to 10 in 0.5 increments that represent higher levels of disability.
次要结局
- Relapse-Free Survival(5 years)
- Expanded Disability Status Scale (EDSS) Improvement(6 months, 1 year, 2 years, 3 years, 4 years, 5 years)
- Scripps Neurological Rating Scale (NRS) Improvement(6 months, 1 year, 2 years, 3 years, 4 years, 5 years)
- Improvement in Quality of Life(6 months, 1 year, 2 years, 3 years, 4 years, 5 years)
- Paced Auditory Serial Addition Test (PASAT) Improvement(6 months, 1 year, 2 years, 3 years, 4 years, 5 years)
- Ambulation Index Improvement(6 months, 1 year, 2 years, 3 years, 4 years, 5 years)
- 9 Hole Peg Test (9-HPT) Improvement(6 months, 1 year, 2 years, 3 years, 4 years, 5 years)
- Change in NMO IgG (aquaporin-4) Antibody Titer(6 months, 1 year, 2 years, 3 years, 4 years, 5 years)
- Improvement in Visual Acuity(6 months, 1 year, 2 years, 3 years, 4 years, 5 years)
研究者
Richard Burt, MD
Professor
Northwestern University