Trial record 2 of 448 for:    Open Studies | "hematopoietic stem cell transplantation"

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by University of California, Los Angeles
Sponsor:
Information provided by (Responsible Party):
Daniel Hommes, MD, University of California, Los Angeles
ClinicalTrials.gov Identifier:
NCT01932658
First received: June 28, 2013
Last updated: February 24, 2014
Last verified: February 2014
  Purpose

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


Condition Intervention Phase
Crohn's Disease
Biological: Hematopoietic stem cell transplantation
Phase 0

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Autologous Hematopoietic Stem Cell Transplantation for Crohn's Disease Treatment

Resource links provided by NLM:


Further study details as provided by University of California, Los Angeles:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Disease remission [ Time Frame: 6 and 12 months post transplant ] [ Designated as safety issue: No ]
    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


Other Outcome Measures:
  • Change in Crohn's disease endoscopic index (SES, Appendix 2) after 6 and 12 months. [ Time Frame: 6 and 12 months post transplant ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 5
Study Start Date: February 2014
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hematopoietic stem cell transplantation
Lymphoablation followed by autologous hematopoietic stem cell transplantation rescue.
Biological: Hematopoietic stem cell transplantation
Lymphoablation followed by hematopoietic stem cell transplantation to rescue the immune system.
Other Name: HSCT

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age between 18 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.

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  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01932658

Contacts
Contact: Ellen Kane, RN 310-206-5706 ekane@mednet.ucla.edu

Locations
United States, California
University of California Los Angeles Not yet recruiting
Los Angeles, California, United States, 90095
Contact: Ellen Kane, RN    310-206-5706    ekane@mednet.ucla.edu   
Sub-Investigator: Welmoed Van Deen, MD         
UCLA Center for Inflammatory Bowel Diseases Recruiting
Los Angeles, California, United States, 90095
Contact: Ellen Kane, RN    310-206-5706    ekane@mednet.ucla.edu   
Principal Investigator: Daniel Hommes, MD PhD         
Sponsors and Collaborators
University of California, Los Angeles
Investigators
Principal Investigator: Daniel W Hommes, MD,PhD University of California, Los Angeles
  More Information

No publications provided

Responsible Party: Daniel Hommes, MD, Principal Investigator, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT01932658     History of Changes
Other Study ID Numbers: UCLA-001836, IRB#12-001836
Study First Received: June 28, 2013
Last Updated: February 24, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by University of California, Los Angeles:
autologous
Lymphoablation
hematopoietic
immune system

Additional relevant MeSH terms:
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases

ClinicalTrials.gov processed this record on September 16, 2014