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

NCT ID: NCT00006055

Last Updated: 2005-06-24

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-03-31

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.

Conditions

Purpura, Schoenlein-Henoch; Graft Versus Host Disease; Anemia, Hemolytic, Autoimmune; Rheumatoid Arthritis; Churg-Strauss Syndrome; Hypersensitivity Vasculitis; Wegener's Granulomatosis; Systemic Lupus Erythematosus; Giant Cell Arteritis; Pure Red Cell Aplasia; Juvenile Rheumatoid Arthritis; Polyarteritis Nodosa; Autoimmune Thrombocytopenic Purpura; Takayasu Arteritis

Keywords

Churg-Strauss syndrome; Schonlein-Henoch purpura; Takayasu arteritis; Wegener's granulomatosis; arthritis & connective tissue diseases; autoimmune hemolytic anemia; cardiovascular and respiratory diseases; disease-related problem/condition; giant cell arteritis; graft versus host disease; hematologic disorders; hypersensitivity vasculitis; immune thrombocytopenic purpura; immunologic disorders and infectious disorders; juvenile rheumatoid arthritis; polyarteritis nodosa; pure red cell aplasia; rare disease; rheumatoid arthritis; systemic lupus erythematosus; vasculitis

Study Design

• Primary Study Purpose: TREATMENT

Interventions

anti-thymocyte globulin

Intervention Type: DRUG

cyclophosphamide

Intervention Type: DRUG

cyclosporine

Intervention Type: DRUG

filgrastim

Intervention Type: DRUG

methylprednisolone

Intervention Type: DRUG

prednisone

Intervention Type: DRUG

Autologous Peripheral Blood Stem Cell Transplantation

Intervention Type: PROCEDURE

Eligibility Criteria

Exclusion Criteria

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

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fairview University Medical Center

OTHER

Sponsor Role: lead

Principal Investigators

Arne Slungaard

Role: STUDY_CHAIR

Fairview University Medical Center

Locations

Fairview University Medical Center

Minneapolis, Minnesota, United States

Countries

United States

Other Identifiers

UMN-MT-1996-15

Identifier Type: -

Identifier Source: secondary_id

UMN-MT-9615

Identifier Type: -

Identifier Source: secondary_id

199/15105

Identifier Type: -

Identifier Source: org_study_id