Autologous Peripheral Blood Stem Cell Transplantation in Patients With Life Threatening Autoimmune Diseases

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Brief Title

Autologous Peripheral Blood Stem Cell Transplantation in Patients With Life Threatening Autoimmune Diseases


Brief Summary

      OBJECTIVES: I. Determine whether there is prompt engraftment after autologous peripheral
      blood stem cell transplantation using filgrastim (G-CSF) mobilization in patients with life
      threatening autoimmune diseases.

      II. Determine the kinetics of T- and B-cell immune reconstitution after a combination of
      timed plasmapheresis, high dose cyclophosphamide and total lymphoid irradiation, and
      posttransplant immunosuppression with cyclosporine in these patients.

      III. Determine whether this treatment regimen beneficially influences the clinical course of
      these patients.
    

Detailed Description

      PROTOCOL OUTLINE: Patients receive filgrastim (G-CSF) SC daily until peripheral blood stem
      cells (PBSC) are collected. On the fifth day of G-CSF therapy, PBSC are collected. Patients
      undergo plasmapheresis on days -9 to -7. Patients receive cyclophosphamide IV on days -6 to
      -3 and total lymphoid irradiation on day -1. PBSC are reinfused on day 0. Following PBSC
      reinfusion, patients receive prophylaxis with oral prednisone or methylprednisolone IV on
      days -1 to 28, antithymocyte globulin IV on days 1-3, and cyclosporine every 12 hours on days
      1-60.

      Patients with autoimmune thrombocytopenia purpura, autoimmune hemolytic anemia, or pure red
      cell aplasia are followed on days 7, 14, 21, 28, 60, and 100, 6 months, and 1, 2, and 5
      years. Patients with rheumatoid arthritis, juvenile rheumatoid arthritis, or systemic lupus
      erythematosus are followed on days 14, 28, 60, and 100, and then every 6 months. Patients
      with vasculitis are monitored for abnormal clinical and laboratory parameters characteristic
      of the individual type of vasculitis.
    


Study Type

Interventional




Condition

Purpura, Schoenlein-Henoch

Intervention

anti-thymocyte globulin


Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

10

Start Date

March 2000



Eligibility Criteria

        Autoimmune thrombocytopenia purpura: platelet count less than 20,000/mm3 Adequate or
        increased marrow megakaryocytes Presence of detectable platelet associated immunoglobulins
        not due to alloreactive antibodies or posttransfusion purpura Prior response to
        immunosuppressive therapy Platelet count chronically less than 20,000/mm3 with petechial
        bleeding or less than 50,000/mm3 with other bleeding OR Any history of life threatening
        hemorrhage Refractory to conventional therapy for at least 21 days Splenectomy At least 1
        additional immunosuppressive therapy applied after splenectomy OR Controlled on
        conventional therapy but at price of unacceptable toxicity: Serious steroid related
        toxicity Absolute neutrophil count less than 500/mm3 25% of time, pure red blood cell
        transfusion dependent or other toxicities (e.g., hemorrhagic cystitis) that are a
        consequence of chronic or cytotoxic therapy Unable to wean from chronic daily or
        intermittent cytotoxic therapy

        Autoimmune hemolytic anemia or pure red cell aplasia, AIHA: Hemolytic anemia Hemoglobin
        less than 10.0 g/dL without transfusion Hemolysis as evidenced by both: Sustained
        reticulocytosis (greater than 125,000/mm3) without evidence of active bleeding or
        increasing hemoglobin Laboratory evidence of hemolysis Positive direct antiglobulin test or
        equivalent immune adherence test No evidence for paroxysmal nocturnal hemoglobinuria
        Negative Ham's test and sucrose hemolysis. For PRCA: Anemia due to selective decrease in
        marrow erythroid precursors Hemoglobin less than 10.0 g/dL without transfusion Severe
        reticulocytopenia (less than 20,000/mm3 despite anemia) Severely decreased marrow erythroid
        precursors Positive marrow coculture with serum or cells or response to immunosuppression
        No evidence for PNH Negative Ham's test and sucrose hemolysis Severe disease: Chronic
        (i.e., greater than 1 year) Transfusion dependent or untransfused hemoglobin less than 8.0
        g/dL Ferritin greater than 2,000 or evidence of organ dysfunction due to iron overload
        Refractory to conventional therapy after all 3 of the following: High dose steroids (at
        least 1 mg/kg) for at least 21 days Splenectomy (except cold reactive antibodies) 1
        additional immunosuppressive therapy OR Controlled on conventional therapy but at price of
        unacceptable toxicity

        Rheumatoid arthritis: Morning stiffness for at least 6 weeks Arthritis of 3 or more joint
        areas Arthritis of hand joints Symmetric arthritis Rheumatoid nodules Serum rheumatoid
        factor Radiographic changes Active rheumatoid disease as evidenced by all of the following:
        Elevated Westergren erythrocyte sedimentation rate Minimum of 16 swollen or tender joints
        using the 28 joint count method Must be at high risk for developing deforming joint disease
        as defined by at least 2 of the following: High titer IgM-IgG rheumatoid factor
        Radiographic evidence of erosive arthritis developing within the first 24 months of
        clinical disease Functional class II or III Refractory to conventional therapy after 12
        months of: Methotrexate used in combination with cyclosporine, hydroxychloroquine, or
        sulfasalazine OR Intramuscular gold therapy (total dose greater than 1.0 g and duration at
        least 6 months) OR Controlled on conventional therapy but at price of unacceptable toxicity

        Juvenile rheumatoid arthritis: Under 16 years of age at onset Arthritis in 1 or more joints
        as defined by swelling or effusion, or presence of 2 or more of the following: Limitation
        of range of motion Tenderness or pain on motion Increased heat Duration of disease 6 weeks
        or longer Onset type defined by type of disease in first 6 months: Polyarthritis (i.e., 5
        or more inflamed joints) Oligoarthritis (i.e., less than 5 inflamed joints) Systemic (i.e.,
        arthritis with characteristic fever) Exclusion of other forms of juvenile arthritis Active
        disease evidenced by 1 of the following: Minimum of 2 swollen or tender joints using the 71
        joint count method Endocardial or myocardial disease, or serositis Anemia or thrombocytosis
        of chronic disease High risk for developing deforming joint disease or evidence of
        potential life threatening involvement for at least 1 internal organ system Radiographic
        evidence of erosive arthritis developing within first 24 months of clinical disease
        Functional class II or III Endocardial, myocardial, pericardial, and/or pleural disease
        Hemoglobin less than 10.0 g/dL or platelet count greater than 600,000/mm3 Refractory to
        conventional therapy after 12 months of methotrexate used in combination with
        hydroxychloroquine, sulfasalazine, azathioprine, cyclosporine, or cyclophosphamide OR
        Controlled on conventional therapy but at price of unacceptable toxicity

        Systemic lupus erythematosus: Malar rash Discoid rash Photosensitivity Oral ulcers
        Arthritis Serositis Renal disorder Neurologic disorder Hematologic disorder Immunologic
        disorder Antinuclear antibody Must have at least 4 of 7 variables on the lupus activity
        scale measured Evidence of potential life threatening involvement of at least 1 internal
        organ system Endocardial and/or myocardial disease Central nervous system disease Pulmonary
        parenchymal disease Renal disease defined as WHO III, IV or V and a high activity and low
        chronicity index Immune mediated cytopenias Refractory to conventional therapy after
        attempts to control disease with at least 2 drugs, including prednisone and 1 of the
        following: Azathioprine Cyclophosphamide (greater than 500 mg/m2 monthly for 6 months)
        Cyclosporine OR Controlled on conventional therapy but at price of unacceptable toxicity

        Vasculitis Definitive diagnosis of 1 of the following forms: Churg-Strauss syndrome Giant
        cell arteritis Henoch-Schonlein purpura Hypersensitivity vasculitis Polyarteritis nodosa
        Takayasu arteritis Wegener's granulomatosis Evidence of active disease defined as
        reversible manifestations of the underlying inflammatory process Must have 1 or more of the
        following: Elevated Westergren erythrocyte sedimentation rate Elevated C reactive protein
        Decrease serum complement levels Evidence of potential life threatening involvement of at
        least 1 internal organ system Endocardial and/or myocardial disease Central nervous system
        disease Pulmonary parenchymal disease Renal disease defined as WHO III, IV or V and a high
        activity and low chronicity index Immune mediated cytopenias Refractory to conventional
        therapy (i.e., failed or relapsed within 6 months) after attempts to control disease with
        at least 2 drugs, including prednisone and 1 of the following: Methotrexate Azathioprine
        Cyclophosphamide Cyclosporine OR Controlled on conventional therapy but at price of
        unacceptable toxicity

        Performance status: ECOG 0-1 ECOG 2 allowed provided symptoms directly related to
        autoimmune disease Hepatic: No history of severe, prior or ongoing chronic liver disease
        Bilirubin less than 2.0 mg/dL AST less than 2 times upper limit of normal (ULN) Alkaline
        phosphatase less than 2 times ULN Renal: Creatinine less than 2.5 mg/dL OR Creatinine no
        greater than 2 times normal baseline for age in pediatric patients Cardiovascular: No
        symptoms of cardiac disease No active ischemic heart disease Ejection fraction greater than
        45% by MUGA No uncontrolled hypertension Pulmonary: FEV1/FVC at least 60% OR Resting PO2 at
        least 80 mm Hg DLCO greater than 50% predicted O2 saturations greater than 94% in children
        unable to perform PFTs Neurologic: No active or ongoing ischemic or degenerative CNS
        disease not attributable to underlying disease Other: Not pregnant No poorly controlled
        diabetes HIV negative
      

Gender

All

Ages

1 Year - 55 Years

Accepts Healthy Volunteers

No

Contacts

Arne Slungaard, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00006055

Organization ID

199/15105

Secondary IDs

UMN-MT-1996-15


Study Sponsor

Fairview University Medical Center


Study Sponsor

Arne Slungaard, Study Chair, Fairview University Medical Center


Verification Date

October 2003