Pilot Study of Stem Cell Transplantation for Children and Young Adults With Refractory Crohn's Disease.
Crohn's Disease
About this trial
This is an interventional treatment trial for Crohn's Disease focused on measuring Crohn's Disease, Hematopoietic stem cell transplantation, Children, Young Adults
Eligibility Criteria
Inclusion Criteria:
All the subjects considered eligible for the study will be screened and reviewed by the Gastroenterology (GI) physicians prior to enrollment (Dedrick Moulton, MD or his designee at Vanderbilt Children's Hospital) 2. Age ≥ 10 and < 30 years 3. Disease status:
- Confirmed diagnosis of Crohn's Disease: Diagnosis of Crohn's disease that has been established based on typical endoscopic/histologic and/or radiological appearances.
- Active disease, defined as: Pediatric Crohn's Disease Activity Index (PCDAI) >30 (see Appendix I) or Crohn's Disease Activity Index (CDAI) of >250 (see Appendix II) at any time within 3 months prior to enrollment and any one of the following- i. Endoscopic evidence of active disease confirmed on histology within 3 months prior to enrollment, or ii. Clear evidence of active small bowel Crohn's disease on small bowel imaging within 3 months prior to enrollment.
Refractory disease- Moderate to severe disease that has been unresponsive to current or prior therapy with mercaptopurine and/or azathioprine (thiopurines), methotrexate and anti-TNF therapy. Patients should have relapsing disease (i.e. ≥ 1 exacerbation/year) or corticosteroid dependence despite current or prior thiopurines, methotrexate and anti-TNF maintenance therapy or clear demonstration of intolerance or toxicity to these drugs. Patients who fail induction therapy with corticosteroids and anti-TNF therapy, and are therefore not eligible to receive maintenance therapy with thiopurines or methotrexate will also be candidates for enrollment.
4. Negative stool culture, C. difficile, and negative CMV pcr (in stool or colonic biopsy). Patients with CMV colitis will receive a trial of anti-viral treatment and only responders will be considered eligible for inclusion.
5. Patients with a prior ileostomy or colostomy may enter the study. For this group of patients', physician's global assessment will be used to assess clinical activity of CD, as Pediatric CDAI and CDAI scoring method may not be representative of disease activity.
6. Patients with abscesses are eligible to enroll once the abscesses or any other significant infection has resolved.
Exclusion Criteria:
- Pregnancy or unwillingness to use adequate contraception during the study- if a woman is of childbearing age.
- HIV infection.
Organ function criteria-
- Renal: creatinine clearance < 50 ml/min/1.73m2 (measured or estimated).
- Cardiac: left ventricular ejection fraction <30% by multigated radionuclide angiography (MUGA) or a shortening fraction of < 25% by cardiac echocardiogram.
- Pulmonary Function tests: DLCO < 30% or patient on oxygen.
- Hepatic: serum bilirubin > 3 mg%; AST and ALT > 3x ULN for the institutional lab.
- Uncontrolled Hypertension (using age based criteria) despite at least 2 anti- hypertensive agents.
Active Infection or risk thereof-
- Current abscess or significant active infection
- Perianal infection is not an exclusion criterion, provided there is drainage with or without placement of drain.
- Abnormal chest x- ray (CXR) consistent with active infection or neoplasm.
- Severe diarrhea due to short small bowel; patients believed to have < 700 mm of small bowel and diarrhea attributable to this will be excluded.
- Patients with toxic megacolon, active bowel obstruction or intestinal perforation.
- Unable to collect minimum of 3 x106/kg CD34+ cell dose. These patients will be excluded from receiving the preparative regimen.
Sites / Locations
Arms of the Study
Arm 1
Experimental
Single Arm: All subjects
Hematopoietic stem cell transplantation