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. 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.
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 2018|
|Estimated Primary Completion Date:||January 2017 (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
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01288053
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|Principal Investigator:||Richard Burt, MD||Northwestern University|