Non-myeloablative Allogeneic Hematopoietic Stem Cell Transplantation (NST) for Patients With Refractory Crohn's Disease
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 2
- 主要终点
- Survival
研究概览
简要总结
Allogeneic transplantation has been a high-risk procedure, although non-myeloablative conditioning regimens (mini-transplantation) minimizes regimen related toxicity. The investigators, therefore, propose a phase I study of matched sibling allogeneic hematopoietic stem cell transplantation with non-myeloablative conditioning. In addition, graft versus host disease (GVHD) will be virtually eliminated by CAMPATH that removes donor T cells from the graft.
The goal is to assess the toxicity/efficacy (phase I) of allogeneic non-myeloablative hematopoietic stem cell transplantation for high-risk Crohn's disease. In simplistic terms, this protocol is designed to ablate an aberrant immune system and then, similar to the use of marrow transplants for immunodeficient patients, reconstitute a new immune system with lymphocyte depleted marrow.
详细描述
PBSC will be mobilized with G-CSF 10 mcg/kg/day (dose may be adjusted down to 5 mcg/kg/day by PI for toxicity, e.g. flu-like symptoms) with stem cell collection beginning on day 4 or 5. Leukapheresis may be repeated up to three consecutive days.
Cyclophosphamide 60 mg/kg/day x 2 days will be given IV over 1 hour in 500 cc of normal saline.
Dosage should be based on the lesser of adjusted body weight or actual weight. Mesna 50mg/day x 2 days will be given IV over 24 hours
CAMPATH-1H 30mg/day x 2 days (no dose adjustment) will be given IV over 2 hours in 100 cc of normal saline. Premedication with Solumedrol 1g IV, Acetaminophen 650mg & benadryl 50mg PO/IV will be given 30-60min before infusion. Also while on CAMPATH, Chlorphenamine 4 mg PO TID, Singular 10 mg PO daily, Pepcid 40 mg PO BID and Claritin 10 mg PO daily will be given, adjusted as needed. These medications can be repeated or changed as needed.
Fludarabine 30mg/m2 daily for 3 days (no dose adjustment) will be given IV over 30 minutes in 100 cc normal saline.
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 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >18 years and less than age 45 years at time of pretransplant evaluation and,
- •Ability to give informed consent.
- •And either A or B A)An established clinical diagnosis of severe CD with disease onset before 16 years old (at least 71 genetic loci predispose to pediatric CD, Limbergen, JV. Annu. Rev. Genom. Human Genet. 2009; 10:89-116) that has failed therapy with prednisone, 5 ASA products and has failed an anti-TNF therapy. Failure is defined as a CDAI (appendix A) 250-400 or a Craig Severity Score that is > 17 (appendix C).
- •B)Relapse after an autologous HSCT with a CDAI (appendix A) 250-400 or a Craig Severity Score that is > 17 (appendix C).
排除标准
- •HIV positive.
- •History of coronary artery disease, or congestive heart failure.
- •Uncontrolled diabetes mellitus or any other illness that in the opinion of the investigators would jeopardize the ability of the patient to tolerate aggressive chemotherapy.
- •Prior history of malignancy except localized basal cell or squamous skin cancer. 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, lactation, inability or unwillingness to pursue effective means of birth control, failure to accept or comprehend irreversible sterility as a side effect of therapy.
- •Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible.
- •FEV 1/FVC < 50% of predicted, DLCO < 50% of predicted.
- •Resting LVEF < 50%.
- •Bilirubin > 2.0 mg/dl, transferase (AST) > 2x upper limit of normal, unless the abnormalities are secondary to Crohn's disease.
- •Serum creatinine > 2.0 mg/dl.
- •Platelet count less than 100,000/ul, ANC less than 1500/ul.
- •Patients presenting with intestinal perforation or toxic megacolon, or a suppurative problem that will require urgent surgery. In addition, the patient may not have any active infection. The presence of intestinal stomas does not exclude the patient from study.
- •Pre-study peripheral blood counts must include a platelet count greater than 100,000/ul and an absolute neutrophil count greater than 1500/ul.
- •Creatinine clearance more than 20% below lower limit of normal for age and sex.
- •Short gut syndrome.
- •Donor eligibility
- •Inclusion criteria
- •Donor must be an HLA 6 out of 6 matched sibling
- •Exclusion criteria of HLA matched sibling donor
- •Physiologic age > 50 years old or <18 years old
- •HIV positive
- •Active ischemic heart disease or heart failure
- •Acute or chronic active hepatitis
- •Uncontrolled diabetes mellitus or any other illness that in the opinion of the investigators would jeopardize the ability of the donor to tolerate stem cell collection
- •Prior history of malignancy except localized basal cell or squamous skin cancer. Other malignancies for which the patient is judged to be cured by local surgical therapy, such as (but not limited to) head and neck cancer, or stage I or II breast cancer will be considered on an individual basis.
- •Positive pregnancy test
- •Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible
- •Major hematological abnormalities such as platelet count less than 100,000/ul, ANC less than 1000/ul
- •Donor has history of Crohn's or ulcerative colitis
结局指标
主要结局
Survival
时间窗: Up to five years
The number of participants who survived treatment
次要结局
未报告次要终点
研究者
Richard Burt, MD
MD
Northwestern University