Phase I Study of Immune Ablation and CD34+ Peripheral Blood Stem Cell Support in Patients With Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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OBJECTIVES: I. Determine the safety of immune ablation with high-dose cyclophosphamide and anti-thymocyte globulin followed by peripheral blood stem cell support in patients with systemic lupus erythematosus.

Detailed Description
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PROTOCOL OUTLINE: Patients receive cyclophosphamide IV over 1 hour for 2 doses. Patients receive filgrastim (G-CSF) subcutaneously (SC) beginning 24 hours after completion of cyclophosphamide and continuing until leukapheresis is complete. Leukapheresis continues daily until target number of cells is harvested. CD 34+ cells are isolated from peripheral blood stem cells (PBSC) in vitro. Patients then receive cyclophosphamide IV over 1 hour on days -5 to -2, anti-thymocyte globulin IV over 10 hours on days -4 to -2, and G-CSF SC beginning on day 0 and continuing until blood counts recover. Patients undergo reinfusion of CD34+ PBSC on day 0. Patients are followed weekly for 90 days, monthly for 1 year, and at 2 years.

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: anti-thymocyte globulin
* Drug: cyclophosphamide
* Drug: filgrastim
* Procedure: CD34+ Peripheral Blood Stem Cell Reinfusion


Participation Criteria
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Eligibility Criteria
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PROTOCOL ENTRY CRITERIA: --Disease Characteristics-- Diagnosis of systemic lupus erythematosus with 1 of the following malignant features: Nephritis (WHO class III or IV) Failed NIH short-course cyclophosphamide therapy Vasculitis/immune complex deposition causing end organ signs or symptoms (e.g., cerebritis, transverse myelitis, pulmonary hemorrhage, cardiac failure, or renal failure) Hematologic cytopenias that are immune mediated and uncontrolled by conservative measures with any of the following: Transfusion-dependent anemia with untransfused hemoglobin less than 8 g/dL Platelet count less than 40,000/mm3 (without transfusions) Granulocyte count less than 1,000/mm3 Catastrophic anti-phospholipid syndrome --Patient Characteristics-- Cardiovascular: LVEF at least 35% No lupus-induced myocarditis No history of unstable angina Pulmonary: FEV1/FVC at least 50% predicted DLCO at least 50% predicted Other: HIV negative No prior or concurrent malignancy except localized basal cell or squamous cell skin cancer No uncontrolled diabetes mellitus No medical illness that would preclude study No psychiatric illness or mental deficiency that would preclude study No known hypersensitivity to E. coli-derived proteins Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: anti-thymocyte globulin|nan|
|Drug: cyclophosphamide|nan|
|Drug: filgrastim|nan|
|Procedure: CD34+ Peripheral Blood Stem Cell Reinfusion|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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arthritis & connective tissue diseases, immunologic disorders and infectious disorders, rare disease, systemic lupus erythematosus