Scientific Abstract
Proposal No. IBD-0155
Principal Investigator: Christopher J. Hawkey, DM
Applicant Organization: University of Nottingham (United Kingdom)
Project Title: Autologous stem cell transplantation: international Crohn’s syndrome (ASTICS) trial
Period of Award: March 1, 2006 – February 29, 2013
We will perform a controlled clinical trial of immunoablation and hemopoietic stem cell transplantation (HSCT) in 40 patients with severe Crohn’s disease. All patients will undergo stem cell mobilization before randomization to an early or late HSCT group. Those receiving early HSCT will be compared over the first year with those whose HSCT has been delayed.
Suitable patients will have relapsing disease (>1 exacerbation/year) despite attempts at control with thiopurines, methotrexate and infliximab maintenance therapy given alone or on separate occasions or clear demonstration of intolerance/toxicity to these drugs. Otherwise, the patients will be in a good enough clinical condition to minimize risks from HSCT. They will undergo extensive phenotyping and genotyping at baseline.
Stem cell mobilization will be achieved using cyclophosphamide 4g/m² (2g/m2 on two consecutive days) followed five days later by filgrastim (G-CSF)10 μg/kg/ for five days.
Leukapheresis will be performed to a target of 3-8 x106 CD34+ cells/kg, starting at latest when PBSC exceed 2 x 109/L.
Approximately one month later, patients randomized to early HSCT will undergo immunoablative conditioning with cyclophosphamide 200 mg/kg (50mg daily on four consecutive days) and anti-thymocyte globulin (rbATG) 2,5 mg/kg/day and intravenous methylprednisolone 1 mg/kg for three days, starting on the third day of cylophosphamide. One day later, thawed stem cells (3-8 x 106/kg CD34 +ve) will be reinfused.
One year later, patients randomized to late HSCT will undergo conditioning and stem cell infusion to the same protocol as the early transplant group. The status of patients undergoing early HSCT will be evaluated after one year and compared to those about to undergo delayed HSCT
By studying 40 patients, the study will have 90% power to detect a rise in the rate of sustained remission from 30% to 75% (80% power for 70%). Other analyses will include quality of life, with further intensive assessments in the second year and formal follow-up to five years.