Autologous Stem Cell Transplant for Refractory Crohn's Disease

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.

Conditions

• Crohn's Disease

Interventions

DRUG

mobilization of stem cells to prepare for Leukapheresis

Cyclophosphomide 2 g/m2 x 2 consecutive days. Filgrastim (G-csf) 10 mcg/kg SC will start 5 days after the last dose of CY and will end the day before the last leukapharesis.

OTHER

Leukapheresis- Collection of stem cells

Placement of an Apheresis Catheter on the day of collection of stem cells. Leukapheresis will be performed on a continuous flow separator machine to target 3-8 x 106 CD34+ cells/kg body weight.

DRUG

Preparative regimen 4-6 weeks after Leukapheresis

Prior to starting medicines, a central venous line will be placed (arm or chest) Cyclophosphamide iv: 50 mg/kg iv over 2 hours Mesna iv (uro-protectant): 36 mg/kg iv over 12 hours r-ATG (Thymoglobulin, Genzyme): 2.5 mg/kg/dose iv over 6 hours on days -3,-2,-1

OTHER

Stem Cell Transplant

Infusion of the(cryopreserved and thawed)peripheral blood stem cells (PBSC)occurs on Day 0. Day +5: start Filgrastim (G-csf) subcutaneous injections Hospitalization in isolation room for 4-5 weeks

DRUG

Low-dose IL-2 administration

IL-2 Subcutaneous injections will start once ANC is \> 500/µL and patient is afebrile (start IL-2 will be approximately day +20)for 6 weeks of treatment. Once patient or parent has learnt the administration and patient is tolerating it well, then the rest of the treatment can be administered at home after discharge with weekly follow up visits.

Sponsors & Collaborators

• Nationwide Children's Hospital

  lead OTHER

Principal Investigators

• Sandeep Soni, MD · Nationwide Children's Hospital

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

12 Years

Max Age

29 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-04-30

Primary Completion

2013-04-30

Completion

2013-04-30