Crohn's Disease Stem Cell Transplantation
Condition: Crohn's Disease
MeSH terms: Crohn Disease
Intervention: Autologous Stem Cell Transplantation
Intervention description: Autologous Stem Cell Transplantation will be performed after conditioning regimen
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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.