Autologous Hematopoietic Stem Cell Transplantation for Crohn's Disease Treatment

Crohn's Disease Clinical Trial

— HSCT  

Official title:

Autologous Hematopoietic Stem Cell Transplantation for Crohn's Disease Treatment

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01932658
• Other study ID #: UCLA-001836
• Secondary ID: IRB#12-001836
• Status: Withdrawn
• Phase: Phase 0
• First received: June 28, 2013
• Last updated: April 13, 2016
• Start date: February 2014
• Est. completion date: March 2017

Study information

• Verified date: April 2016
• Source: University of California, Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety and potential clinical benefit of lymphoablation followed by autologous HSCT rescue in therapy refractory Crohn's disease

Description:

The treatment of Crohn's disease has proven to be quite efficacious in the majority of patients with the timely use of combination therapies for remission induction (corticosteroids and/or biologics) and maintenance of disease control (immunosuppressives and/or biologics). However, a proportion of patients fail to achieve complete and long term disease control and often require multiple intestinal surgeries with a risk of developing short bowel syndrome. Lymphoablation followed by hematopoietic stem cell transplantation to rescue the immune system has been proposed as an alternative strategy to induce long term disease control in this high risk population. It has been demonstrated that despite the potential toxicity and morbidity associated with the procedure, the benefit-risk ratio is favorable. Hence, we propose to offer HSCT to selected CD patients, and to study mechanisms of reducing T cell autoreactivity which will hopefully lead to more focused therapeutic approaches in the future.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 2017
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 7 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Age between 7 and 50 years (patients aged 50 - 70 can participate up to the principal investigators discretion).

2. Confirmed diagnosis of active Crohn's disease:

1. Diagnosis of Crohn's disease based on typical radiological appearances and or typical histology at least 6 months prior to screening.

2. Active disease at the time of registration to the trial, defined as

i)Crohn's Disease Activity Index (CDAI) > 250, and ii)Two of the following:

1. elevated C-Reactive Protein (CRP)

2. endoscopic evidence of active disease confirmed by histology

3. clear evidence of active small bowel Crohn's disease on Computed tomography (CT) or Magnetic Resonance (MR) enterography.

3. Unsatisfactory course despite 3 immunosuppressive agents (usually azathioprine, methotrexate and infliximab, adalimumab and/or certolizumab) in addition to corticosteroids. Patients should have relapsing disease (i.e. 1 exacerbation/year) despite thiopurines, methotrexate and/or infliximab/adalimumab/certolizumab maintenance therapy or clear demonstration of intolerance / toxicity to these drugs.

4. Current problems unsuitable for surgery or patient at risk for developing short bowel syndrome.

5. Informed consent:

1. Prepared to undergo additional study procedures as per trial schedule

2. Patient has undergone intensive counseling about risks

Exclusion Criteria:

1. Pregnancy or unwillingness to use adequate contraception during the study, in women of childbearing age. Unwillingness of using appropriate contraceptive measures in males.

2. Concomitant severe disease

1. renal: creatinine clearance < 30 mL/min (measured or estimated)

2. cardiac: clinical evidence of refractory congestive heart failure; left ventricular ejection fraction < 40% by multigated radionuclide angiography (MUGA) or cardiac echo; chronic atrial fibrillation necessitating oral anticoagulation; uncontrolled ventricular arrhythmia; pericardial effusion with hemodynamic consequences as evaluated by an experienced echo cardiographer.

3. pulmonary: diffusion capacity <40%

4. psychiatric disorders including active drug or alcohol abuse

5. concurrent or recent history of malignant disease (excluding non-melanoma skin cancer)

6. uncontrolled hypertension, defined as resting systolic blood pressure = 140 and/or resting diastolic pressure = 90 despite at least 2 anti-hypertensive agents.

7. uncontrolled acute or chronic infection with HIV, Human T-Lymphotropic virus (HTLV-1 or 2), hepatitis viruses or any other infection the investigators consider a contraindication to participation.

8. other chronic disease causing significant organ failure.

3. Infection or risk thereof:

1. Current clinical relevant abscess or significant active infection.

2. Perianal fistula without free drainage. Perianal fistulas is not an exclusion provided there is natural free drainage or a seton suture(s)have been placed.

3. History of tuberculosis or currently at risk for tuberculosis

4. Quantiferon Gold test result or other investigations that the investigators regard as evidence of active tuberculosis.

5. Abnormal chest X-ray (CXR) consistent with active infection or neoplasm.

4. Significant malnutrition: Body Mass Index (BMI) = 18, serum albumin < 20g/l.

5. Previous poor compliance.

6. Concurrent enrollment in any other protocol using an investigational drug or hematopoietic growth factor up to four weeks before study entry.

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

Biological:
• Hematopoietic stem cell transplantation
Lymphoablation followed by hematopoietic stem cell transplantation to rescue the immune system.

Locations

Country	Name	City	State
United States	UCLA Center for Inflammatory Bowel Diseases	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, Los Angeles

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Crohn's disease endoscopic index (SES, Appendix 2) after 6 and 12 months.	Change in inflammatory bowel disease questionnaire (IBD-Q) score (Appendix 3) after HSCT.; Change in work productivity and activity impairment (WPAI) score (Appendix 4) after HSCT	6 and 12 months post transplant	No
Primary	The primary outcome to be measured is safety and clinical benefit of lymphoablation followed by autologous HSCT rescue in therapy refractory Crohn's disease.	Safety will be evaluated by the amount of related adverse events. All adverse events will be recorded in a standardized way and their relationship to the study protocol will be assessed at various short and long term time points.	Month 1- 24 months post transplant	Yes
Secondary	Disease remission	Second, to determine clinical benefit, the percentage of patients in sustained disease remission at 0, 2, 4, 6, 12 and 24 months post HSCT will be determined. Sustained disease remission is defined as a CDAI < 150 (Appendix 1) without the use of corticosteroids. In addition, mucosal healing will be assessed during ileocolonoscopy at 6 and 12 months following HSCT using the SES endoscopic index (see under secondary endpoints	6 and 12 months post transplant	No