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

NCT02225795 | Withdrawn DMC

• 1 other identifier: BMT 12
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Crohn's Disease

Keywords

Crohn's Disease; Hematopoietic stem cell transplantation; Children; Young Adults

Outcome Measures

Primary Outcomes (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).

  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.

  first 100 days post HSCT

Secondary Outcomes (4)

• 1. Incidence of viral reactivations - CMV and EBV

  First 100 days post HSCT

• 2. Incidence of invasive fungal infections

  within first 100 days post HSCT

• 3. Immune reconstitution after HSCT

  Until the study is closed which is anticipated to be approximately 3 years.

• 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.

  1 year post transplant

Study Arms (1)

Single Arm: All subjects

EXPERIMENTAL

Hematopoietic stem cell transplantation

Other: Hematopoietic stem cell transplantation

Interventions

Hematopoietic stem cell transplantation OTHER

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

Also known as: ANTI-THYMOCYTE GLOBULIN (Rabbit) NSC# 720095, CYCLOPHOSPHAMIDE (Cytoxan) NSC #26271, MESNA - INJECTION NSC #113891, GCSF: Filgrastim: 5 mcg/kg iv, Stem-cell mobilization, Leukapheresis

Single Arm: All subjects

Eligibility Criteria

• Age: 10 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• \. 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.
• \. Patients with abscesses are eligible to enroll once the abscesses or any other significant infection has resolved.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• TriStar Health: lead

MeSH Terms

Conditions

Crohn Disease

Interventions

Hematopoietic Stem Cell Transplantation; Antilymphocyte Serum; Cyclophosphamide; Hematopoietic Stem Cell Mobilization; Leukapheresis

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytapheresis; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques

Study Officials

• Haydar Frangoul, MD

  TriStar Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director, Pediatric Hematology Oncology

Study Record Dates

• First Submitted: July 28, 2014
• First Posted: August 26, 2014
• Study Start: August 1, 2014
• Primary Completion: August 1, 2019
• Study Completion: December 1, 2019
• Last Updated: February 7, 2018

Record last verified: 2018-02