Non-myeloablative Autologous Hematopoietic Stem Cell Transplantation in Patients With Chronic Inflammatory Demyelinating Polyneuropathy: A Phase II Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- Number of Participants With Survival
研究概览
简要总结
Chronic inflammatory demyelinating polyneuropathy is disease believed to be due to immune cells, cells which normally protect the body, but are now attacking the nerves in the body. As a result, the affected nerves fail to respond, or respond only weakly, to stimuli causing numbing, tingling, pain, and progressive muscle weakness.The likelihood of progression of the disease is high. This study is designed to examine whether treating patients with high dose cyclophosphamide (a drug which reduces the function of the immune system) and ATG (a protein that kills the immune cells that are thought to be causing disease), followed by return of the previously collected blood stem cells will stop the progression of CIDP. Stem cells are undeveloped cells that have the capacity to grow into mature blood cells, which normally circulate in the blood stream. The purpose of the high dose cyclophosphamide and ATG is to destroy the cells in the immune system. The purpose of the stem cell infusion is to evaluate whether this treatment will produce a normal immune system that will no longer attack the body.
详细描述
Selection of the Regimen for Immunosuppressive Therapy
Cyclophosphamide with ATG is a common conditioning regimen with two decades of experience in the treatment of aplastic anemia, and has been used safely without reported mortality in the treatment of autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis.Cy / ATG is not associated with late malignancies or cataracts. Both cyclophosphamide and anti-thymocyte globulin (horse or rabbit ATG) are potent immunosuppressive agents. ATG contributes additional immunosuppression without additional cytotoxicity. ATG given shortly pre-transplant will contribute to the elimination of host T lymphocytes that survive cyclophosphamide SLE, an autoimmune disease responsive to cyclophosphamide, responds well to a CY / ATG conditioning regimen, but we have recently found that patients with either systemic lupus erythematosus (SLE) or neuromyelitis optica respond faster and may have more durable remissions to a regimen of "rituxan sandwich" in which rituxan is infused before and after standard cytoxan, rATG. For these reasons, "rituxan sandwich" will be the conditioning regimen utilized in this study.
5.2 Method of Harvesting Stem Cells
Based on the experience of the pilot studies, the current protocol will mobilize stem cells with granulocyte-colony stimulating factor (G-CSF) and collect stem cells by apheresis, with subsequent bone marrow harvest performed only if needed to supplement the peripheral blood stem cells (PBSC). Based on experience of autoimmune flares in patients receiving G-CSF alone for mobilization, patients will be mobilized with cyclophosphamide 2.0 g/m2 and G-CSF 5-10 mcg/kg.
5.3 Cyclophosphamide
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
- 未提供
排除标准
- •Any evidence of hereditary cause for neuropathy that is known or likely hereditary demyelination neuropathy because of family history, foot deformity, mutilation of hands or feet, retinitis pigmentosa, ichthyosis, or liability to pressure palsies.
- •Diphtheria, drug, or toxin exposure likely to be cause of neuropathy
- •Conditions in which the pathogenesis of the neuropathy may be different from CIDP such as: Lyme disease (Borrelia burgdorferi infection), POEMS syndrome, Osteosclerotic myeloma, malignancies such as Waldenstrom macroglobulinemia, and Castleman's)
- •Multiple myeloma
- •HIV positive
- •Insulin dependent Diabetes mellitus
- •Chronic active hepatitis
- •Age > 65 years old or < 18 years old
- •Significant end organ damage such as (not caused by CIDP):
- •Left ventricular ejection fraction (LVEF) <40% or deterioration of LVEF during exercise test on multigated acquisition scan (MUGA) or echocardiogram.
- •Untreated life-threatening arrhythmia.
- •Active ischemic heart disease or heart failure or myocardial infarction within the last 6 months
- •Diffusing capacity of lung for carbon monoxide (DLCO) <40% or forced expiratory volume at one second (FEV1) / forced expiratory volume (FEV) < 50%
- •Serum creatinine >2.
- •Liver cirrhosis, transaminases > 2 x of normal limits or bilirubin >2.0 unless due to Gilbert disease.
- •Prior history of malignancy except localized basal cell or squamous skin cancer or other localized cancer considered cured only by surgery
- •Positive pregnancy test, inability or unwillingness to pursue effective means of birth control, or failure to willingly accept or comprehend irreversible sterility as a side effect of therapy.
- •Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible.
- •Inability to give informed consent.
- •Major hematological abnormalities such as platelet count less than 100,000/ul or absolute neutrophil count (ANC) less than 1000/ul.
- •Failure to collect at least 2.0 x 106 cluster of differentiation 34 (CD34+) cells by apheresis and, if necessary, bone marrow harvest is a contraindication to treatment, i.e., receiving the conditioning regimen.
结局指标
主要结局
Number of Participants With Survival
时间窗: up to 5 years
Survival of participants who survived the treatment and up to 5 years post treatment.
次要结局
- Disease Improvement - Medication Free Remission(6 months, 1, 2, 3, 4 and 5 years post transplant)
- Disease Improvement - Ambulatory Assistance(pre transplant, 6 months, 1, 2, 3, 4 and 5 years post transplant)
- Change in Disability and Strength Functional Scales(Pre Transplant, 6 months, 1, 2, 3, 4 and 5 years post transplant)
研究者
Richard Burt, MD
MD
Northwestern University