High-dose Cyclophosphamide for Severe Refractory Crohn Disease
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Evaluation of safety of the High-Dose Cyclophosphamide (HDC) protocol
研究概览
简要总结
This research is being done to see if people with Crohn's disease who receive high-dose cyclophosphamide have an improvement of their disease, how long the benefit may last, and how safe cyclophosphamide is. This study is for patient with medically refractory disease that is not easily amenable to surgery.
Cyclophosphamide is an FDA-approved chemotherapy medication that is also frequently used to treat autoimmune illness; use of cyclophosphamide for autoimmune disease is not approved by the FDA. An autoimmune illness is when the immune system mistakenly attacks self, targeting the cells, tissues, and organs of a person's own body. There are many different autoimmune diseases and they can each affect the body is different ways. Crohn's disease is an autoimmune disease that primarily affects the small and large intestines. High dose-cyclophosphamide has been successfully used to treat Crohn's, primarily as part of a conditioning regimen for autologous stem cell transplantation. However, this therapy is limited in Crohn's because of it's serious infectious risks. This current study involves using high-dose cyclophosphamide without need for stem cell transplantation. This appears to be a safer approach in other autoimmune illnesses that have been studied.
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥ 18 years of age, males and females will be eligible
- •Moderate to severe Crohn's Disease (CD) with CDAI > 220, in addition to evidence of ulceration on ileocolonoscopy or active disease on small bowel imaging (in patients with an ostomy, CDAI criteria do not apply)
- •Disease progression (primary or secondary non-responder, or reaction to) to at least one anti-tumor necrosis factor (TNF) agent (infliximab, adalimumab, certolizumab pegol), and additionally had disease progression despite one of the following immunosuppressant drugs: azathioprine, 6-mercaptopurine, methotrexate, cyclosporine, natalizumab, vedolizumab
- •Willingness to participate in a clinical trial
- •Approval by Enrollment Panel, who will collectively decide on the appropriateness of possible study study participants
排除标准
- •Pregnant or nursing women
- •Sexually active men and women who do not agree to use effective means of birth control during treatment period
- •Evidence of primarily fibrostenosing disease without active inflammatory disease on disease staging
- •Co-morbid conditions including cardiac disease with an ejection fraction of < 45%, chronic renal failure with serum creatinine > 2.0, liver disease with total bilirubin > 2.0, (excluding hyperbilirubinemia secondary to Gilbert's disease) or transaminitis > 3x upper limit of normal.
- •History of serious allergic reaction to cyclophosphamide
- •History of malignancy in the last 5 years (excluding non-melanomatous skin cancers)
- •Patients who are pre-terminal
- •Toxic megacolon
- •Active infection
- •White blood cell count < 3000 cells/ul, platelets < 100K / ul, hemoglobin < 10.0 g/dL
- •Any use of thiopurines, methotrexate or anti-TNF agents in the previous four weeks prior to treatment
研究组 & 干预措施
High-dose Cyclophosphamide
High-dose Cyclophosphamide
干预措施: High-dose Cyclophosphamide (Drug)
结局指标
主要结局
Evaluation of safety of the High-Dose Cyclophosphamide (HDC) protocol
时间窗: 3 Years
Tablulation of serious adverse events associate with the HDC protocol
次要结局
- HDC-Induced Steroid-free remission(3 Years)
- HDC-Induced Mucosal Healing(3 Years)
- Improvement in patient reported quality of life(3 years)
- Molecular Mechanisms of High-dose Cyclophosphamide (HiCy) Therapy(3 Years)