COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC:

Get the latest research information from NIH: Menu

Pilot Study of Stem Cell Transplantation for Children and Young Adults With Refractory Crohn's Disease.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02225795
Recruitment Status : Withdrawn (recruitment difficulty)
First Posted : August 26, 2014
Last Update Posted : February 7, 2018
Information provided by (Responsible Party):
Haydar Frangoul, TriStar Health

Brief Summary:

This is a study for people with Crohn's Disease (CD) that are not responsive to standard treatment. CD is a chronic disease with an auto-immune component that goes away and relapses over the years and causes lifelong impairment of health and quality of life. Regardless of the therapy used some patients remain seriously ill with active disease after multiple therapeutic options have been exhausted. There is currently no drug that will cure CD. Drug treatment is focused on controlling symptoms. Another treatment is to perform surgery but again this does not lead to cure and is often linked to infection, short gut syndrome problems and psycho-social and cosmetic issues. Therefore, a treatment that does not involve surgery or long-term drug treatment may be beneficial especially to young adults.

Hematopoietic stem cell transplantation (HSCT) has been of value in other auto-immune diseases and it is possible that it could be of value in CD. This is a pilot study to determine if HSCT is safe and effective for children and young adults with severe CD. For this study the stem cells will come from the patient. This is called an autologous transplant. The patient will undergo collection and storage of his/her peripheral blood stem cells (PBSC). The patient will be given drugs to move (or mobilize) the stem cells from his/her bone marrow into his/her blood where they will be collected on a machine called apheresis (similar to dialysis.) The cells will be stored and given back to the patient about 1 month after collection.

Condition or disease Intervention/treatment Phase
Crohn's Disease Other: Hematopoietic stem cell transplantation Not Applicable

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of Autologous Hematopoietic Stem Cell Transplantation With Post-transplant Cyclophosphamide for Children and Young Adults With Refractory Crohn's Disease.
Study Start Date : August 2014
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease

Arm Intervention/treatment
Experimental: Single Arm: All subjects
Hematopoietic stem cell transplantation
Other: Hematopoietic stem cell transplantation

Immuno-ablative regimen for HSCT:

Day Treatment

  • 6 r-ATG 2 mg/kg
  • 5 r-ATG3 2 mg/kg
  • 4 r-ATG3 2 mg/kg
  • 3 Cyclophosphamide with Mesna
  • 2 Cyclophosphamide with Mesna
  • 1 REST 0 PBSC infusion

    • 3 Cyclophosphamide with Mesna
    • 4 Cyclophosphamide with Mesna
    • 6 Start GCSF
Other Names:
  • CYCLOPHOSPHAMIDE (Cytoxan) NSC #26271
  • GCSF: Filgrastim: 5 mcg/kg iv
  • Stem-cell mobilization
  • Leukapheresis

Primary Outcome Measures :
  1. To determine the feasibility and toxicity of immunoablation with HSCT and post-HSCT infusion of cyclophosphamide in children and young adults with refractory Crohn's disease (CD). [ Time Frame: first 100 days post HSCT ]
    This is a composite outcome to determine the feasibility and toxicity of immunoablation with HSCT and post-HSCT infusion of cyclophosphamide in children and young adults with refractory Crohn's disease (CD). Death (transplant related mortality, TRM) and severe non-hematologic toxicity (≥ grade 3 toxicity; NCI Toxicity Criteria version 4.0) within the first 100 days after HSCT will be monitored to meet this end-point.

Secondary Outcome Measures :
  1. 1. Incidence of viral reactivations - CMV and EBV [ Time Frame: First 100 days post HSCT ]
  2. 2. Incidence of invasive fungal infections [ Time Frame: within first 100 days post HSCT ]
  3. 3. Immune reconstitution after HSCT [ Time Frame: Until the study is closed which is anticipated to be approximately 3 years. ]
    3. Immune reconstitution after HSCT lymphocyte subpopulations (absolute number of CD3, CD4, CD8 and CD19 cells), immunoglobulin levels (IgG) and CD4+ CD25+ CD127+ regulatory T cells (Treg) populations on day +30 , +60 , +100, day +180 and yearly post-HSCT.

  4. 4. Evaluate the efficacy and benefit of HSCT in this population at 1 year post HSCT, by serial assessments of clinical activity of CD, assessment of disease severity- CDAI scores and length of steroid free remissions. [ Time Frame: 1 year post transplant ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   10 Years to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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:

  1. Confirmed diagnosis of Crohn's Disease: Diagnosis of Crohn's disease that has been established based on typical endoscopic/histologic and/or radiological appearances.
  2. 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.
  3. 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:

  1. Pregnancy or unwillingness to use adequate contraception during the study- if a woman is of childbearing age.
  2. HIV infection.
  3. 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.
  4. Uncontrolled Hypertension (using age based criteria) despite at least 2 anti- hypertensive agents.
  5. Active Infection or risk thereof-

    1. Current abscess or significant active infection
    2. Perianal infection is not an exclusion criterion, provided there is drainage with or without placement of drain.
    3. Abnormal chest x- ray (CXR) consistent with active infection or neoplasm.
  6. Severe diarrhea due to short small bowel; patients believed to have < 700 mm of small bowel and diarrhea attributable to this will be excluded.
  7. Patients with toxic megacolon, active bowel obstruction or intestinal perforation.
  8. Unable to collect minimum of 3 x106/kg CD34+ cell dose. These patients will be excluded from receiving the preparative regimen.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02225795

Sponsors and Collaborators
TriStar Health
Layout table for investigator information
Principal Investigator: Haydar Frangoul, MD TriStar Health
Layout table for additonal information
Responsible Party: Haydar Frangoul, Medical Director, Pediatric Hematology Oncology, TriStar Health Identifier: NCT02225795    
Other Study ID Numbers: BMT 12
First Posted: August 26, 2014    Key Record Dates
Last Update Posted: February 7, 2018
Last Verified: February 2018
Keywords provided by Haydar Frangoul, TriStar Health:
Crohn's Disease
Hematopoietic stem cell transplantation
Young Adults
Additional relevant MeSH terms:
Layout table for MeSH terms
Crohn Disease
Inflammatory Bowel Diseases
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Antilymphocyte Serum
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists