Official Title: “Crohn's Disease Non-Myeloablative Autologous Hematopoietic Stem Cell Transplantation (CDNST) Versus Standard Therapy”

Crohn's disease (CD) is a chronic illness, immunologically mediated, probably induced by the exposure of the intestine to an antigen or antigens similar to the intestine, to which immunologic tolerance is lost or a dysregulated immunity ensues. The disease has a variable course, from a mild, intermittently active illness requiring only symptomatic therapy to a fulminant illness requiring potentially dangerous immunosuppressive therapy, surgery or both.

The molecular defect causing CD has not been characterized, but probably involves aberrant T cell function. Although CD often responds to immunosuppressive medication including corticosteroids, azathioprine and 6-mercaptopurine, to anti inflammatory drugs such as 5 aminosalicylate (5 ASA), or to some antimicrobial agents, including metronidazole, no therapy has been curative. In patients with severe CD, who have been unresponsive to corticosteroids, azathioprine, 5 ASA, metronidazole, and infliximab, we propose to compare the efficacy of Crohn's disease non-myeloablative autologous hematopoietic stem cell transplantation (CDNST) to standard therapy. Subsequent disease activity will be followed by (1) Crohn's disease activity index (CDAI), (2) a more global severity index, the Crohn's Severity Index, (3) type and amount of therapy for CD, and (4) clinical, hematologic and biochemical studies.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: April 2010

Intervention(s) in this Clinical Trial

• Procedure: stem cell transplantation
  • Autologous Hematopoietic Stem Cell Transplantation will be performed on all participants randomized to transplant arm.

Primary Measures

• CDAI
  • Time Frame: Clinical remission defined as a CDAI less than 150 and clinical improvement defined as decline in CDI> or = 70 one year following entry.
    Safety Issue?: Yes

Inclusion Criteria:

• Age 18 years or older and less than age 55 years at time of pretransplant evaluation.
• An established clinical diagnosis of severe CD that has failed therapy with prednisone, azathioprine, 5 ASA products and metronidazole, and has failed an anti-TNF alpha inhibitor. Failure is defined as a CDAI (appendix A) 225-400.
• Pre-study peripheral blood counts must include a platelet count greater than 100,000/ul and an absolute neutrophil count greater than 1500/ul.
• In those randomized to receive the transplant, a stem cell harvest greater than 2.0 x 106 CD34 cells/kg is required.
• Ability to give informed consent.

Exclusion Criteria:

• 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 < 40%.
• Bilirubin > 2.0 mg/dl, transferase (AST) > 2x upper limit of normal.
• 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.
• Splenomegaly (palpable spleen on physical exam).
• Inability to collect > 2.0 x 106 CD34+ cells/kg.
• Positive pregnancy test.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 55 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Northwestern University

Overall Clinical Trial Officials and Contacts

Robert Craig, MD Principal Investigator Northwestern University  

Overall Contact: Dzemila Spahovic, MD 312-908-0059 d-spahovic@northwestern.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00271947

Study ID Number: CD Randomized

ClinicalTrials.gov Identifier: NCT00271947

Health Authority: United States: Food and Drug Administration