Autologous Stem Cell Transplant for Refractory Crohn's Disease

• Status: Withdrawn
• Trial end date: 2013-04-01
• Target enrollment: 0
• Participant gender: All

Summary

Crohn's disease is an 'auto-immune' disorder of the gut. In this condition the body's own immune system is fighting its gut and causing inflammation and other symptoms. Patients who are refractory (not responding) to the medications usually used to control Crohn's disease (medicines like steroids, azathioprine, methotrexate, cyclophosphamide and antibodies like Infliximab), may consider being part of this study.

In this study, the investigators plan to wipe out (ablate) the 'faulty immune system' with medicines (immune-ablation) and then give back the patients own stored stem cells (that have been collected before) - a procedure called autologous (self) stem cell transplant (ASCT). Once the new immune system regrows again from the stem cells, it is hoped that the 'faulty' immune cells do not return again and do not fight the gut leading to remission from symptoms of Crohn's disease. The aim of this treatment therefore, is to reset or re-program the immune system, so that it does not fight the patient's own body.

Currently, there are very few trials and experience with this procedure in children and young adults. There have been a few studies that have shown benefit of ASCT procedure in adult patients. In some patients, the benefit lasted for 1-5 years; but 1 in 5 (20%) participants were not taking their medications for the Crohn's disease even 5 years after ASCT. Other 80% needed medications again, but in most cases with better disease control.

In order to potentially improve the long term outcomes of ASCT, the investigators are adding another medication (in addition to those used in adult studies) called IL-2 (Aldesleukin), which will be given as an every-other-day injection under the skin (subcutaneous) at very low doses for 6 weeks after the ASCT and can be taken at home. Low dose IL-2 is known to increase a type of immune cell called T-regulatory cells (Tregs) that make immune cells less reactive to self. Study doctors believe that increased population of Tregs after ASCT may lead to a better control of Crohn's disease- higher percentage of cures or disease control for a longer period of time compared to the previous adult trials.

Therefore, the goals of this study are-

1. To see if ASCT can be used safely and can provide substantial benefit in young adults who have refractory Crohn's disease.

2. To see if addition of IL-2 after the ASCT is safe and effective.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Nationwide Children's Hospital
• Treatments: Aldesleukin; Cyclophosphamide; Thymoglobulin

Criteria

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.