Hematopoietic Stem Cell Support in Patients With Autoimmune Bullous Skin Disorders

This study has been terminated.
(sponsor stopped the study because of lack of elligible participants)
Sponsor:
Information provided by (Responsible Party):
Richard Burt, MD, Northwestern University
ClinicalTrials.gov Identifier:
NCT00278642
First received: January 16, 2006
Last updated: April 4, 2013
Last verified: April 2013
  Purpose

Autoimmune Bullous Skin Disorders are believed to be due to immune cells, cells that normally protect the body and are now causing damage to the body. This study is designed to examine whether treating patients with high dose cyclophosphamide (a drug which reduces the function of the immune system) together with anti-thymocyte globulin (a protein that kills the immune cells that are thought to be causing your disease), followed by return of the previously collected special blood cells (stem cells) will result in improvement of this disease. Stem cells are undeveloped cells that have the capacity to grow into mature blood cells, which normally circulate in the blood stream. The purpose of the intense chemotherapy is to destroy the cells in the immune system which may be causing this skin disease. The purpose of the stem cell infusion is to restore the body's blood production, which will be severely impaired by the high dose chemotherapy and anti-thymocyte globulin.


Condition Intervention Phase
Pemphigus
Biological: Hematopoietic stem cell transplantation
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: High Dose Cyclophosphamide & ATG With Hematopoietic Stem Cell Support in Patients With Autoimmune Bullous Skin Disorders: A Phase I Trial

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Percent surface area involved New skin or mucosal blister development Immune suppressive medication requirements Survival [ Time Frame: 5 years after transplant ] [ Designated as safety issue: Yes ]

Enrollment: 1
Study Start Date: September 2002
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: stem cell transplantation Biological: Hematopoietic stem cell transplantation
Autologous hematopoietic stem cell transplantation

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Less than chronologic age 60 years at the time of pre-transplant evaluation.
  2. An established diagnosis of an autoimmune skin disorder that includes any of the following:

    1. pemphigus vulgaris
    2. pemphigus foliaceus

    Diagnosis of bullous skin lesions will be based on history and physical, skin biopsy (light microscopy and indirect fluorescence), indirect immunofluorescence titer, BP 180 and 230 titers, Desmolglein-3 and Desmoglein-1 antibody, and photograph.

  3. Patients who failed corticosteroids (equivalent dosage of prednisone 0.5 mg/kg/day for more than 3 months), and at least two of the following: azathioprine, mycophenolate mofetil, gold, tetracycline (or minocycline), cyclosporin, methotrexate, gold, or plasmapheresis. Failure is defined as the inability to wean steroids to less than 0.5 mg/kg/day.
  4. Potential candidates must have involvement of more than 10% of skin body surface area, involvement of one or more mucosal lesions, or recurrent infections requiring more than two hospitalizations in which the source of the infection was due to bullous skin disease.
  5. All candidates must be evaluated by two dermatologists, Dr. Joan Guitart and Dr. Joaquin Brieva, who must concur that the patient has refractory disease that may, in their clinical judgement, be associated with a 5-10% mortality if not controlled.
  6. A minimum of 2.0 x 106 CD34+ cells/kg after selection are necessary to proceed to transplant.

Exclusion Criteria:

  1. Individuals less than 18 years of age.
  2. Significant end organ damage such as:

    1. LVEF <40% or deterioration of LVEF during exercise test on MUGA or echocardiogram.
    2. Untreated life-threatening arrhythmia.
    3. Active ischemic heart disease or heart failure.
    4. DLCO <45% or FEV1/FEV < 50%.
    5. Serum creatinine > 2.5 mg/dl.
    6. Liver cirrhosis, transaminases >3x of normal limits or bilirubin >2.0 unless due to Gilberts disease.
  3. HIV positive.
  4. Uncontrolled diabetes mellitus, or any other illness that in the opinion of the investigators would jeopardize the ability of the patient to tolerate aggressive treatment.
  5. Prior history of malignancy except localized basal cell or squamous skin cancer. Other malignancies for which the patient is judged to be cured by local surgical therapy, such as (but not limited to) head and neck cancer, or stage I or II breast cancer will be considered on an individual basis.
  6. Positive pregnancy test, inability or unable to pursue effective means of birth control, or failure to willingly accept or comprehend irreversible sterility as a side effect of therapy.
  7. Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible.
  8. Inability to give informed consent.
  9. Major hematological abnormalities such as platelet count less than 100,000/ul, or ANC less than 1000/ul.
  10. Presence of infected skin lesions. All skin lesions should be free of suppurative exudate.
  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: NCT00278642

Locations
United States, Illinois
Northwestern University, Feinberg School of Medicine
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Richard Burt, MD
Investigators
Principal Investigator: Richard Burt, MD Northwestern University
  More Information

No publications provided

Responsible Party: Richard Burt, MD, MD, Northwestern University
ClinicalTrials.gov Identifier: NCT00278642     History of Changes
Other Study ID Numbers: DIAD Derm.Auto2001
Study First Received: January 16, 2006
Last Updated: April 4, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Skin Diseases
Skin Diseases, Vesiculobullous

ClinicalTrials.gov processed this record on October 20, 2014