Hematopoietic Stem Cell Support in Vasculitis

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Northwestern University
Sponsor:
Information provided by (Responsible Party):
Richard Burt, MD, Northwestern University
ClinicalTrials.gov Identifier:
NCT00278512
First received: January 15, 2006
Last updated: February 4, 2014
Last verified: February 2014
  Purpose

The systemic vasculitis is a wide-ranging group of diseases that are characterized by the presence of blood vessel inflammation (1). Despite this common feature, each type of vasculitis has a unique variety of clinical manifestations that influences its degree of disease severity and ultimately its management. Immunosuppressive therapy forms the foundation of treatment for almost all forms of systemic vasculitis.

The systemic necrotizing vasculitis (SNV) are a subset of vasculitis with significant morbidity and mortality (2). The SNV are Wegener's granulomatosis, allergic angiitis and granulomatosis (AAG) (also known as Churg-Strauss syndrome), polyarteritis nodosum (PAN), microscopic polyangiitis (MPA), and overlap syndrome. In spite of modern therapeutic immune suppressive agents, there remains a not inconsequential morbidity and mortality associated with SNV. The current standard therapy for SNV is chronic oral cyclophosphamide (1-3 mg/kg/day) and corticosteroids (3-6). Transplant doses of cyclophosphamide at 200 mg/kg infused over 4 days is the most common worldwide transplant regimen for systemic lupus erythematosus (SLE) (7). Like SLE, SNV are cyclophosphamide responsive disease. We, therefore, propose a trial of high dose cyclophosphamide with anti-thymocyte globulin (ATG) for patients with SNV.


Condition Intervention Phase
Vasculitis
Biological: Hematopoietic Stem Cell Transplant
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: High Dose Immune Suppression With Hematopoietic Stem Cell Support in Refractory Vasculitis, Necrotizing Vasculitis, Neurovascular Behcet's Disease, and Sjogren's Syndrome

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Survival;Change in Birmingham vasculitis activity score (BVAS) (8,9); Change in Vasculitis Damage Index (VDI) (10) [ Time Frame: 5 years after transplant ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 10
Study Start Date: August 2003
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hematopoietic Stem Cell Transplant
Hematopoietic Stem Cell Transplant will be performed on eligible patients
Biological: Hematopoietic Stem Cell Transplant
Hematopoietic Stem Cell Transplant will be performed after conditioning
Other Name: Hematopoietic Stem Cell Transplantation

  Eligibility

Ages Eligible for Study:   16 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 1. Age 16 to 60 years old at the time of pretransplant evaluation.
  • 2. An established diagnosis of systemic necrotizing vasculitis (Wegener's granulomatosus, polyarteritis nodosum (PAN), allergic angiitis granulomatosus (AAG, also known as Churg Strauss syndrome), microscopic polyangiitis (MPA), or overlap syndrome)Temporal arteritis, or mixed cryoglobulinemia or primary central nervous system vasculitis AND failure of corticosteroids and any of the following at least 6 months of oral or IV cytoxan, rituximab, or cellcept. (Failure defined as: a) patients with a high disease activity and involvement of internal organs as measured by increased FFS > 2 and/or BVAS > 20, or b) patients who develop recurrent flares with subsequent progressive organ damage.)

OR

Neurovascular Behcets with recurrent oral and/or genital lesions confirmed by culture to be herpes negative, MRI findings consistent with CNS vasculitis, recurrent neurological symptoms, and clinical confirmation by a Neurologist (e.g., Dr. Rama Gourimeni) AND failure of at least 3 months of oral or IV cytoxan.

OR

Pulmonary or neurovascular Sjogrens with positive SSA/SSB confirmed by a rheumatologist and neurologist (if CNS involved) or pulmonologist (if lungs involved) and either recurrent neurologic attacks or progressive pulmonary compromise (dyspnea on exertion, decreased DLCO or CT findings of active disease) despite at least 6 months of intravenous monthly pulse cyclophosphamide.

  • 3. Patient eligibility must be confirmed by two Rheumatologists. For patients with neurovascular Behcets, eligibility need only be confirmed by a neurologist.
  • 4. A minimum CD34+ cell dose of 2.0 x 106/kg post-selection.

Exclusion Criteria:

  • 1. Significant end organ damage such as:

    1. LVEF <40% or deterioration of LVEF during exercise test on MUGA or echocardiogram unless due to active disease.
    2. Untreated life-threatening arrhythmia.
    3. Active ischemic heart disease or heart failure.
    4. DLCO < 40% of predicted value unless due to active disease.
    5. Serum creatinine > 2.5 mg/dl, unless due to active disease.
    6. Liver cirrhosis, transaminases >3x of normal limits, or bilirubin >2.0 unless due to Gilberts disease.
  • 2. HIV positive.
  • 3. 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.
  • 4. 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.
  • 5. Positive pregnancy test, inability or unable to pursue effective means of birth control, failure to willingly accept or comprehend irreversible sterility as a side effect of therapy.
  • 6. Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible.
  • 7. Inability to give informed consent.
  • 8. Active infection, excluding asymptomatic bacteruria or vaginal candidiasis.
  • 9. Active hepatitis B (HBSAg positive) or active hepatitis C (PCR positive blood lymphocytes).
  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: NCT00278512

Contacts
Contact: Dzemila Spahovic, MD 312-695-4960 d-spahovic@northwestern.edu

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

No publications provided

Responsible Party: Richard Burt, MD, MD, Northwestern University
ClinicalTrials.gov Identifier: NCT00278512     History of Changes
Other Study ID Numbers: DIAD Vasculitis.Auto2002
Study First Received: January 15, 2006
Last Updated: February 4, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Vasculitis
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on September 22, 2014