Allogeneic Blood Stem Cell Transplantation for Patients With Life-Threatening Systemic Lupus Erythematosus

Not Recruiting

Trial ID: NCT00325741


The Stanford Medical Center Division of Immunology and Rheumatology and the Division of Blood and Marrow Transplantation (BMT) are enrolling patients with severe systemic lupus erythematosus (SLE) that is resistant to standard treatment (prednisone and cyclophosphamide \[Cytoxan\]) into a new study to determine if they can be successfully treated with a blood stem cell transplantation obtained from an appropriate donor. Donors will be human leukocyte antigen (HLA)-matched healthy brothers or sisters. For patients without sibling HLA-matches, a search for donors will be initiated through the US and International Donor Registries. Eligible patients must be at least 18 years old and have SLE with progressive kidney, lung, heart, or central nervous system disease that has not responded to standard therapy. Patients will be treated for two weeks to prepare them for the infusion of blood stem cells that are obtained from their HLA-matched donor. Patients will initially be treated with immunosuppressive drugs, which will be gradually withdrawn at approximately 6 months after transplantation. The goal of this study is to replace the abnormal immune cells of the SLE affected patient that causes the disease with normal immune cells that are generated from the transplant blood stem cells from the healthy donor.

Official Title

Allogeneic Hematopoietic Cell Transplantation for Patients With Life-Threatening Systemic Lupus Erythematosus Using a Non-Myeloablative Regimen of Total Lymphoid Irradiation and Anti-Thymocyte Globulin

Stanford Investigator(s)

Judith Shizuru
Judith Shizuru

Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)


Inclusion Criteria:

* Meet the American College of Rheumatology (ACR) criteria for classification of SLE (i.e., at least 4 of the 11 criteria; see Appendix 2 of the protocol for more information)
* SLE disease activity index (SLEDAI) greater than 20 (i.e., active, multi-system SLE; see Appendix 3 of the protocol for more information)
* History of one or more of the following conditions that have not responded to conventional therapy with pulse intravenous or oral cyclophosphamide and corticosteroids:

1. Lupus pneumonitis with a progressive decline in lung function tests and evidence of oxygen desaturation on effort in which the lung CT scans and chest X-rays show active disease without irreversible extensive scarring
2. Diffuse alveolar hemorrhage associated with oxygen desaturation with persistent abnormalities of the lung CT scan or X-rays that have not resolved after conventional therapy
3. Central nervous system lupus that has resulted in neurological deficits requiring hospitalization with a brain CT scan and/or brain MRI and shows evidence of lupus activity without extensive irreversible lesions
4. Lupus nephritis with a progressive decline in the creatinine clearance that has not fallen below 25 ml/min in which a biopsy shows active disease without irreversible extensive scarring
* Refractory disease, as determined by failure of the following two conditions:

1. Trial of corticosteroids (equivalent to prednisone 0.5 mg/kg/day for 2 months and/or at least 3 pulses of methylprednisolone 1,000 mg over 3 days) on at least one occasion within the 6 months prior to study entry
2. Trial of cyclophosphamide of at least 500 mg/m² IV pulse at least 3 times or oral cyclophosphamide for at least 30 days
* Must have a fully HLA identical sibling or a matched unrelated donor
* Willing to use contraception throughout the study and for 12 months following treatment

Exclusion Criteria:

* Allergic to rabbit ATG
* Score of less than 60% on Karnofsky Performance Scale
* Organ dysfunction, defined as follows:

1. Cardiac function ejection fraction less than 40% or uncontrolled malignant arrhythmias or clinical evidence of congestive heart failure (New York Class 3-4, see Appendix 4 of the protocol for more information)
2. Pulmonary diffusion capacity (DLCO) less than 30% of predicted
3. Liver function abnormalities with direct bilirubin levels greater than 3.0 mg/dL on two repeated tests and/or transaminases greater than 4 times the upper limit of normal
4. Measured creatinine clearance of less than 40 ml/min (24 hour urine collection)
* Pregnant


drug: Hematopoietic Cell Transplantation

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Judith A. Shizuru, MD, PhD