Non-myeloablative Allogeneic Hematopoietic Stem Cell Transplantation (NST) for Patients With Refractory Crohn's Disease
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. The primary endpoint to be considered in this study is:
- Duration of disease remission defined as a CDAI < 100. 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.
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 45 mg/kg/day x 4 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.
CAMPATH-1H 30mg/day x 3 days (no dose adjustment) will be given IV over 2 hours in 100 cc of normal saline. Premedication with acetaminophen 650mg & benadryl 50mg PO/IV will be given 30-60min before infusion. These medications can be repeated as needed.
Fludarabine 25mg/m2 daily for 3 days (no dose adjustment) will be given IV over 30 minutes in 100 cc normal saline.
Hydration approximately 2 liters/m2/day should begin 6 hours before cyclophosphamide and continue until 24 hours after the last cyclophosphamide dose. BID weights will be obtained. Amount of fluid can be modified based on patient's fluid status.
G-CSF will be continued until absolute neutrophil count reaches at least 1,000/ul.
Cyclosporin will be started on day -2 at 200 mg po BID and adjusted by HPLC levels to between 150 - 250 or by toxicity (e.g., tremor, renal insufficiency, TTP, etc.). CSA will be continued for 30 days unless stopped for toxicity or needed to maintain donor engraftment.
Mycophenolate mofetil (MMF)* 1g PO/IV q 12hrs will be started on day -2 and continued for 6 months or longer if needed for engraftment. Then, dosage may be reduced to 250 mg or 500mg q 12hrs for toxicity.
Cyclosporine and MMF guidelines dosage and duration can be modified according to investigators discretion based on side effects, renal function, CBC and GVHD status.
Biological: Allogeneic Stem Cell Therapy
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Non-myeloablative Allogeneic Hematopoietic Stem Cell Transplantation (NST) for Patients With Refractory Crohn's Disease|
- Survival [ Time Frame: Five years ] [ Designated as safety issue: Yes ]Survival will be measured at 6 months, 1 , 2, 3, 4, and 5 years after transplant.
- Remission [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]Duration of disease remission is defined as a CDAI (Crohn's Disease Activity Index) < 100, and will be measured at 6 months, 1, 2, 3, 4 and 5 years after transplant.
- CDAI [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]Crohns Disease Activity Index will be measured at 6 months, 1, 2, 3, 4 and 5 years after transplant.Remission is defined as a CDAI < 100,Relapse is defined as a CDAI > 150
- CCSI [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]CCSI (Craig Crohn's Severity Index) will be performed at 6 months, 1, 2, 3, 4, and 5 years after the transplant.
- IBDQ [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]Inflammatory Bowel Disease Questionnaire (IBDQ)will be performed at 6 months, 1, 2, 3, 4, and 5 years after the transplant.
|Study Start Date:||January 2010|
|Estimated Study Completion Date:||January 2016|
|Estimated Primary Completion Date:||January 2015 (Final data collection date for primary outcome measure)|
Experimental: Allogeneic Stem Cell Therapy
Allogeneic Stem Cell Therapy will be performed after conditioning
Biological: Allogeneic Stem Cell Therapy
Donor stem cells will be given to subject diagnosed with Crohn's disease
Please refer to this study by its ClinicalTrials.gov identifier: NCT01288053
|Contact: Dzemila Spahovic, MDemail@example.com|
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|Principal Investigator: Richard Burt, MD|
|Principal Investigator:||Richard Burt, MD||Northwestern University|