Autologous Stem Cell Transplant for Refractory Crohn's Disease

This is an interventional treatment trial for Crohn's Disease focused on measuring Crohn's Disease, Autologous Hematopoietic Stem cell Transplant, Cyclophosphamide, IL-2, Aldesleukin, Proleukin, PCDAI Read More

Inclusion Criteria:

• Age ≥ 12 and < 30 years
• Confirmed diagnosis of Crohn's Disease -Pediatric Crohn's Disease Activity Index (PCDAI) >30 or Crohn's Disease Activity Index (CDAI) of >250 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 Crohn's 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.
• Current active disease and problems not amenable to surgery or patient at risk for developing short bowel syndrome.
• 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.
• Female patients of childbearing potential must have a documented negative serum pregnancy test within 2 weeks prior to starting the mobilization regimen.
• Patients with a prior ileostomy or colostomy may enter the study. For this group of patients', physician's global assesment will be used to assess clinical activity of CD, as Pediatric CDAI and CDAI scoring method may not be representative of disease activity.
• 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-

  1. Renal: creatinine clearance < 50 ml/min/1.73m2 (measured or estimated).
  2. Cardiac: left ventricular ejection fraction <30% by multigated radionuclide angiography (MUGA) or a shortening fraction of < 25% by cardiac echocardiogram.
  3. Pulmonary Function tests: DLCO < 30% or patient on oxygen.
  4. 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-

1. Current abscess or significant active infection (see 6.2.9 above)
2. Perianal infection is not an exclusion criterion, provided there is drainage with or without placement of seton.

3. Abnormal chest x ray (CXR) consistent with active infection or neoplasm.

   • Severe diarrhea due to short small bowel; pateints 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.
   • Lack of insurance payer approval.
   • Unable to collect minimum cell dose from Leukapheresis required for transplant. These patients will be excluded from receiving the preparative regimen.