Scientific Abstract

Proposal No. IBD-0170R
Principal Investigator:  Robert M. Craig, M.D.
Applicant Organization:  Northwestern University (Chicago, Illinois, U.S.A.)
Project Title: Immune ablation and hematopoietic stem cell support in patients with refractory Crohn’s. A randomized, controlled study.
Period of Award:  June 1, 2006 – September 30, 2008

We will ascertain the role of immune ablation and hematopoietic autologous stem cell transplantation in refractory Crohn's disease and compare it to a randomized control group of patients. We will compare response and safety of the experimental therapy to standard therapy in patients with refractory Crohn's disease. Subjects with a Crohn's severity index of 17 or greater (defined in published manuscripts), who have failed usual management, including immunosuppression and infliximab, will be randomized to receive the experimental therapy versus standard therapy. Standard therapy could include 5-ASA products, antibiotics, immunosuppressive therapy, anti-TNF infusions, surgery and corticosteroids, decided in concert with the managing physicians and the investigators. In both the experimental therapy and the standard therapy groups, the stem cells will be harvested immediately from the peripheral blood following cyclophosphamide treatment and GCSF administration. The CD34 positive stem cells will be selected by the Isolex system. Following recovery of the bone marrow, the subjects randomized to the experimental arm will undergo the conditioning regimen of cyclophosphamide and anti-lymphocyte CD52 antibody (Campath 1H). Their stem cells will be re-infused and GCSF will be administered. Platelet and red blood cell transfusions, antibiotics and other supportive therapy are used as needed. The patients in the control group will not receive stem cell infusion. The subjects in both groups will be followed with clinical observation, colonoscopy, upper endoscopy if initial upper endoscopy shows Crohn's, small intestinal radiography, hemoglobin, CRP, serum albumin, sedimentation rate, CDAI, ASCA and the Crohn's severity index at six months and one, two and three years following entry. A fall in the severity index of ten points at one year will be considered an excellent response. Subjects randomized to receive standard therapy who have not shown a fall in the severity index of ten, one-year following entry, will be offered stem cell therapy and will be followed as a third group for the next three years.