Autologous Hematopoietic Stem Cell Transplant for Crohn's Disease
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Treatment-related mortality
研究概览
简要总结
This study is a new Phase II trial to assess the toxicity and efficacy of autologous hematopoietic stem cell transplantation (HSCT) utilizing a new non-myeloablative conditioning regimen in patients with high-risk Crohn's disease (CD). The regimen will include low-dose immunosuppressive therapy and a targeted antibiotic for six to twelve months post-HSCT.
详细描述
The autologous hematopoietic stem cell transplantation (HSCT) in this study utilizes a new non-myeloablative conditioning regimen in patients with high-risk Crohn's disease (CD). The regimen includes two types of chemotherapy (cyclophosphamide and fludarabine) as well as alemtuzumab. The regimen will include low-dose immunosuppressive therapy with tacrolimus (Prograf) for one year post-HSCT in attempt to prevent relapse and improve long-term remission. Patients will also receive rifaximin (Xifaxan) for six months post-HSCT to target abnormal intestinal microbiota that may trigger intestinal inflammation. The ability of these experimental treatments to stop relapses and progression (worsening) of Crohn's disease 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 49 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 years and less than age 50 years at the time of pre-transplant evaluation
- •Ability to give informed consent
- •An established clinical diagnosis of severe Crohn's Disease* that has failed therapy with prednisone or budesonide (Entocort) and either a or b below:
- •At least two anti-tumor necrosis factor (TNF) drugs (e.g., infliximab (Remicade), adalimumab (Humira), or certolizumab pegol (Cimzia))
- •One anti-TNF drug as above and either vedolizumab (Entyvio) or ustekinumab (Stelara)
- •Severe Crohn's Disease is defined as a CDAI (see Appendix A) of 250 to 400 or a Craig's Crohn's Severity Index (CCSI, see Appendix B) that is > 17.
排除标准
- •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
- •Prior history of malignancy (except localized basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix). Other malignancies for which the patient is judged to be cured by local surgical therapy, such as head and neck cancer, or stage I breast cancer will be considered on an individual basis
- •Positive pregnancy test, inability to pursue effective means of birth control, or failure to willingly accept or comprehend irreversible sterility as a side effect of therapy
- •HIV positive
- •Hepatitis B or C positive
- •Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible
- •Untreated life-threatening cardiac arrhythmia on EKG or 24-hour holter or history of coronary artery disease or congestive heart failure
- •Left ventricular ejection fraction (LVEF) <50%
- •Forced vital capacity (FVC) <60% of predicted after bronchodilator therapy (if necessary) or diffusing capacity of the lungs for carbon monoxide (DLCO) hemoglobin corrected <60 % predicted
- •Serum creatinine >2 mg/dl
- •24-hour urine creatinine clearance <90
- •Liver transaminases >2x of normal limits, or bilirubin >2 mg/dl unless due to Crohn's Disease
- •Major hematological abnormalities such as platelet count < 100,000/ul or absolute neutrophil count (ANC) < 1500/ul
- •Failure to collect at least 2 x10^6 cluster of differentiation 34 (CD34+) cells/kg
- •Any active infection
- •Known hypersensitivity to mouse, rabbit, or E. coli derived proteins
- •Short Bowel Syndrome defined as intestinal dysfunction with the presence of significant malabsorption of both macronutrients and micronutrients or when gastrointestinal function is inadequate to maintain nutrient and hydration status without intravenous or enteral supplementation.
- •History of anorexia nervosa (serum albumin ≤ 20 g/L, body mass index ≤ 18)
- •Patients presenting with intestinal perforation or toxic megacolon or a problem that will require urgent surgery. The presence of intestinal stomas, strictures, or fistulae does not exclude the patient from study.
- •Unable or unwilling to stop using and/or smoking tobacco products
- •Abnormal peripheral blood cytogenetics
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 fludarabine, cyclophosphamide, mesna, and alemtuzumab. Granulocyte-colony stimulating factor (G-CSF) will be administered post-transplant until engraftment. Rifaximin and tacrolimus will be administered for 6 and 12 months, respectively, beginning one day before the infusion of stem cells.
干预措施: Fludarabine (Drug)
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cell Therapy will be performed as follows: Autologous stem cells will be infused after conditioning with fludarabine, cyclophosphamide, mesna, and alemtuzumab. Granulocyte-colony stimulating factor (G-CSF) will be administered post-transplant until engraftment. Rifaximin and tacrolimus will be administered for 6 and 12 months, respectively, beginning one day before the infusion of stem cells.
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 fludarabine, cyclophosphamide, mesna, and alemtuzumab. Granulocyte-colony stimulating factor (G-CSF) will be administered post-transplant until engraftment. Rifaximin and tacrolimus will be administered for 6 and 12 months, respectively, beginning one day before the infusion of stem cells.
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 fludarabine, cyclophosphamide, mesna, and alemtuzumab. Granulocyte-colony stimulating factor (G-CSF) will be administered post-transplant until engraftment. Rifaximin and tacrolimus will be administered for 6 and 12 months, respectively, beginning one day before the infusion of stem cells.
干预措施: Alemtuzumab (Drug)
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cell Therapy will be performed as follows: Autologous stem cells will be infused after conditioning with fludarabine, cyclophosphamide, mesna, and alemtuzumab. Granulocyte-colony stimulating factor (G-CSF) will be administered post-transplant until engraftment. Rifaximin and tacrolimus will be administered for 6 and 12 months, respectively, beginning one day before the infusion of stem cells.
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 fludarabine, cyclophosphamide, mesna, and alemtuzumab. Granulocyte-colony stimulating factor (G-CSF) will be administered post-transplant until engraftment. Rifaximin and tacrolimus will be administered for 6 and 12 months, respectively, beginning one day before the infusion of stem cells.
干预措施: Rifaximin (Drug)
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cell Therapy will be performed as follows: Autologous stem cells will be infused after conditioning with fludarabine, cyclophosphamide, mesna, and alemtuzumab. Granulocyte-colony stimulating factor (G-CSF) will be administered post-transplant until engraftment. Rifaximin and tacrolimus will be administered for 6 and 12 months, respectively, beginning one day before the infusion of stem cells.
干预措施: Tacrolimus (Drug)
结局指标
主要结局
Treatment-related mortality
时间窗: 3 years
Treatment-related mortality
Overall survival
时间窗: 3 years
Survival of participants
Clinical remission
时间窗: 6 months, 1 year, 2 years, 3 years
Change of Crohn's Disease Activity Index CDAI ≤ 150, Harvey-Bradshaw Index (HBI) ≤4, may be on immune suppressive drugs
Complete remission
时间窗: 1 year, 2 years, 3 years
Change of Clinical, endoscopic, and histologic remission on no immune modulating drugs
次要结局
- Histologic remission on colonoscopy with biopsy(6 months, 1 year, 2 years, 3 years)
- Endoscopic remission(6 months, 1 year, 2 years, 3 years)
- Craig's Crohn's Severity Index(6 months, 1 year, 2 years, 3 years)
- Endoscopic severity scales(6 months, 1 year, 2 years, 3 years)
- Drug-free clinical remission(1 year, 2 years, 3 years)
- Inflammatory Bowel Disease Questionnaire(6 months, 1 year, 2 years, 3 years)
- Crohn's Disease Endoscopic Index of Severity (CDEIS)(6 months, 1 year, 2 years, 3 years)
- Relapse-free survival(6 months, 1 year, 2 years, 3 years)
- Stool markers(6 months, 1 year, 2 years, 3 years)
- Quality of life short form Survey (SF-36)(6 months, 1 year, 2 years, 3 years)
研究者
Richard Burt, MD
Division Chief, Immunotherapy and Autoimmune Diseases
Northwestern University