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Autologous Hematopoietic Stem Cell Transplantation for Crohn's Disease Treatment (HSCT)

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ClinicalTrials.gov Identifier: NCT01932658
Recruitment Status : Withdrawn (patients insurance would not cover the cost of the study procedures)
First Posted : August 30, 2013
Last Update Posted : April 15, 2016
Sponsor:
Information provided by (Responsible Party):
Daniel Hommes, MD, University of California, Los Angeles

Tracking Information
First Submitted Date  ICMJE June 28, 2013
First Posted Date  ICMJE August 30, 2013
Last Update Posted Date April 15, 2016
Study Start Date  ICMJE February 2014
Estimated Primary Completion Date March 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 29, 2013)
The primary outcome to be measured is safety and clinical benefit of lymphoablation followed by autologous HSCT rescue in therapy refractory Crohn's disease. [ Time Frame: Month 1- 24 months post transplant ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 29, 2013)
Disease remission [ Time Frame: 6 and 12 months post transplant ]
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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: August 29, 2013)
Change in Crohn's disease endoscopic index (SES, Appendix 2) after 6 and 12 months. [ Time Frame: 6 and 12 months post transplant ]
  1. Change in inflammatory bowel disease questionnaire (IBD-Q) score (Appendix 3) after HSCT.
  2. Change in work productivity and activity impairment (WPAI) score (Appendix 4) after HSCT
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Autologous Hematopoietic Stem Cell Transplantation for Crohn's Disease Treatment
Official Title  ICMJE Autologous Hematopoietic Stem Cell Transplantation for Crohn's Disease Treatment
Brief 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
Detailed 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Crohn's Disease
Intervention  ICMJE Biological: Hematopoietic stem cell transplantation
Lymphoablation followed by hematopoietic stem cell transplantation to rescue the immune system.
Other Name: HSCT
Study Arms  ICMJE Experimental: Hematopoietic stem cell transplantation
Lymphoablation followed by autologous hematopoietic stem cell transplantation rescue.
Intervention: Biological: Hematopoietic stem cell transplantation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: April 13, 2016)
0
Original Estimated Enrollment  ICMJE
 (submitted: August 29, 2013)
5
Estimated Study Completion Date  ICMJE March 2017
Estimated Primary Completion Date March 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

    -

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 7 Years to 70 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01932658
Other Study ID Numbers  ICMJE UCLA-001836
IRB#12-001836 ( Other Identifier: UCLA IRB )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Daniel Hommes, MD, University of California, Los Angeles
Study Sponsor  ICMJE University of California, Los Angeles
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Daniel W Hommes, MD,PhD University of California, Los Angeles
PRS Account University of California, Los Angeles
Verification Date April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP