Allogeneic Blood Stem Cell Transplantation for Patients With Life-Threatening Systemic Lupus Erythematosus
Recruitment status was: Recruiting
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 Patients will initially be treated with immunosuppressive drugs, which will be gradually withdrawn at approximately 6 months after transplantation.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.
Lupus Erythematosus, Systemic
Procedure: Hematopoietic Cell Transplantation
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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|
- Time to achieve complete remission (participants that are off all immunosuppressive therapy without clinical or laboratory evidence of active disease) [ Time Frame: Measured within the first year ] [ Designated as safety issue: No ]
- Percentage of patients with stable chimerism in all blood and immune cell lineages [ Time Frame: Measured within the first year ] [ Designated as safety issue: No ]
- Percentage of participants with acute or chronic graft-versus-host disease [ Time Frame: Measured within the first year ] [ Designated as safety issue: Yes ]
|Study Start Date:||June 2004|
|Estimated Study Completion Date:||July 2010|
|Estimated Primary Completion Date:||July 2010 (Final data collection date for primary outcome measure)|
Procedure: Hematopoietic Cell Transplantation
The purpose of this study is to evaluate the effectiveness of allogeneic blood stem cell transplantation in individuals with life-threatening SLE. A non-bone marrow ablative regimen consisting of total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG) will be used to condition the recipients for transplantation. Appropriately HLA-matched donors will undergo "mobilization" of their peripheral blood mononuclear cells using G-CSF and collection by apheresis.
The preparative regimen will consist of targeted low dose radiation of lymphoid tissue administered over a 2-week period of time. During the first week of irradiation, the patients will also receive the ATG treatment. Patients will be admitted to the in-patient service for the first 5 days of the transplant preparative regimen while receiving the ATG infusion. Patients will be discharged for the second half of the preparative regimen and followed in the out-patient clinic thereafter. Patients will start immunosuppressive treatment with cyclosporine and mycophenolate mofetil prior to the infusion of mobilized peripheral blood stem cells. The mycophenolate mofetil will be stopped at approximately 1 month post-transplantation and the cyclosporine will be tapered beginning at 2 months post-transplantation and discontinued by 6 months in the presence of stable blood chimerism and the absence of graft-versus-host disease. In the pre-transplant and post-transplant setting, patients will be evaluated by an integrated team of Rheumatology and BMT physicians. During the first 21-28 days post-transplantation, these evaluations will be performed on a daily or every other day basis. Patients will be clinically assessed and evaluated for engraftment of donor cells and disease response. Patients will then be followed as needed with maximum time between evaluations of 1 to 2 weeks in the first 100 days, and then monthly for 6 months and every 6 months to 12 months thereafter.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00325741
|United States, California|
|Stanford University School of Medicine|
|Stanford, California, United States, 94305|
|Principal Investigator:||Judith A. Shizuru, MD, PhD||Stanford University|