Hematopoietic Stem Cell Support in Vasculitis
Condition: Vasculitis
MeSH terms: Vasculitis
Intervention: Autologous Stem Cell Transplant; Allogeneic Stem Cell Transplant; Cyclophosphamide; ATG (rabbit); G-CSF; Campath-1h; Fludarabine; Tacrolimus; Mesna
Intervention description: Autologous Hematopoietic Stem Cell Transplant will be performed after conditioning; Allogeneic Stem Cell Transplant will be performed after conditioning; Causes prevention of the cell division; A rabbit polyclonal antibody to lymphocyte; Hematopoietic growth factor; Humanized monoclonal antibody against CD52 antigen; inhibits DNA synthesis or repair; immune suppressive drug; Mesna is a drug used to protect the bladder from the effects of the chemotherapy drugs
Intervention MeSH terms: Cyclophosphamide; Fludarabine; Alemtuzumab; Tacrolimus; Thymoglobulin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 16 Years
Maximum age: 60 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility 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
             granulomatous, polyarteritis nodosum (PAN), allergic angiitis granulomatous (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 10e6/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).