Lupus Immunosuppressive/Immunomodulatory Therapy or Stem Cell Transplant (LIST)
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|ClinicalTrials.gov Identifier: NCT00230035|
Recruitment Status : Withdrawn (Recommended by DSMB due to lack of accrual)
First Posted : September 30, 2005
Last Update Posted : February 1, 2013
|First Submitted Date ICMJE||September 28, 2005|
|First Posted Date ICMJE||September 30, 2005|
|Last Update Posted Date||February 1, 2013|
|Study Start Date ICMJE||September 2005|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||Mortality resulting from treatment, underlying disease, or unrelated causes [ Time Frame: At Month 30 ]|
|Original Primary Outcome Measures ICMJE
||Mortality resulting from treatment, underlying disease, or unrelated causes at Month 30|
|Change History||Complete list of historical versions of study NCT00230035 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Lupus Immunosuppressive/Immunomodulatory Therapy or Stem Cell Transplant (LIST)|
|Official Title ICMJE||A Randomized, Open Label, Phase II Multicenter Study of Non-Myeloablative Autologous Transplantation With Auto-CD34+HPC Versus Currently Available Immunosuppressive/Immunomodulatory Therapy for Treatment of Systemic Lupus Erythematosus|
Systemic lupus erythematosus, also known as lupus or SLE, is a chronic, multisystem, autoimmune disease in which the body's internal system of defense attacks its own normal tissues. This abnormal autoimmune response can result in damage to many parts of the body, especially the skin, joints, lungs, heart, brain, intestines, and kidneys. Both genetic and environmental risk factors are involved in the development of lupus, but these are poorly understood.
SLE has an overall 10-year survival between 80 and 90%. However, we estimate that severe lupus not responding to the usual available treatments has a 50% mortality rate in 10 years. Kidney problems occur in 30% to 50% of lupus patients and may progress to kidney failure. Kidney disease due to lupus occurs more frequently in African-Americans and Hispanics. Lupus can affect many parts of the body and cause damage, but the severe form can result in death from kidney disease; cardiovascular disease, specifically atherosclerosis; central nervous system disease; and infections.
Currently, no single standard therapy for treatment of severe SLE exists. Usually physicians prescribe an aggressive regimen of one or a combination of immunosuppressive/immunomodulatory treatments. This approach to therapy for all forms of severe SLE derives largely from studies of lupus nephritis. Current treatment, although effective in many people, are not effective in all patients and are associated with drug-induced morbidity. The design of the control arm for this study reflects the current status of treatment of SLE in the academic setting. Investigators may choose from a list of commonly used and currently available immunosuppressive/immunomodulatory treatments to optimize the treatment of their patients, based on their past treatment history and response to those treatments. Study treatments may consist of corticosteroids, cyclophosphamide (CTX), azathioprine, methotrexate, cyclosporine, mycophenolate mofetil (MMF), plasmapheresis, intravenous immunoglobulin (IVIG), rituximab, and leflunomide. Treatment may be changed as frequently and as necessary within the first year of the study to control the manifestations of SLE in each patient. New therapies that become available during the course of this trial may be added to the list of approved medications for this study.
In response to the absence of a uniformly effective treatment for severe lupus, autologous hematopoietic stem cell transplantation (HSCT) has been proposed as a potential therapy. Hematopoietic stem cells are immature blood cells that can develop into all of the different blood and immune cells the body uses. Researchers believe that resetting the immune system may stop or slow down the progression of the disease. The main purpose of this study is to compare two ways of treating SLE: 1) high-dose immunosuppressive therapy (HDIT) followed by HSCT and 2) currently available immunosuppressive/immunomodulatory therapies.
SLE is a chronic, multisystem, inflammatory autoimmune disease in which the body's immune cells wrongly attack its own tissues. It is defined by the presence of circulating antinuclear antibodies that are directed against nucleosomal DNA-histone complexes, native double-stranded DNA (dsDNA), small nuclear ribonucleoproteins (Sm and RNP), single-stranded DNA, and phospholipids moieties on platelets and other tissues, indicating a failure of the regulatory systems involved in maintenance of immunologic tolerance to self-antigens. Despite use of currently available therapies, patients experience relapses of their lupus. Over time, patients develop significant morbidity from the disease as well as from medications, including glucocorticoids, used for treatment. The main purpose of this study is to compare two ways of treating SLE: 1) high-dose immunosuppressive therapy (HDIT) followed by HSCT and 2) currently available immunosuppressive/immunomodulatory therapies.
Corticosteroid dosage tapering will be monitored closely; the schedule for tapering will be the same in both groups. To reduce the possibility of disease flare. a slow tapering of 10% per month will occur for the first six months. Tapering will continue in a prescribed manner to achieve a dose equivalent of 10 mg/day of prednisone or less by one year post-treatment.
All participants will have monthly follow-up visits for 30 months after treatment has been initiated. Study visits will include a physical exam, clinical assessments, rheumatology evaluations, and blood and urine collections. Participants will be asked to complete questionnaires assessing their lupus disease. Neuropsychiatric assessments, echocardiogram, CT scan of brain, renal biopsy, pulmonary function test, dual-energy x-ray absorptiometry scan (DEXA scan), magnetic resonance imagery scan, electromyograph scan (EMG), bone marrow biopsy and aspiration and lumbar puncture may occur at selected visits, based on each individual's manifestations of lupus and clinical indication. Participants will also receive certain vaccinations at selected visits. Participants will be contacted by phone each and every week throughout the study. There will be an extension period for those patients that have completed their treatment and follow-up visits during the study's 5-year duration. Participants will be contacted via telephone, e-mail, or visit every 3 months to assess their use of concomitant medications and immunosuppressive/immunomodulatory therapy and corticosteroids.
Five treatment centers across the United States, all leaders in the fields of transplantation and rheumatology, are participating in this research study.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 2|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Condition ICMJE||Systemic Lupus Erythematosus|
|Study Arms ICMJE||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Withdrawn|
|Actual Enrollment ICMJE
|Original Enrollment ICMJE
|Study Completion Date ICMJE||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages ICMJE||18 Years to 60 Years (Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00230035|
|Other Study ID Numbers ICMJE||DAIT SCSLE-01|
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||National Institute of Allergy and Infectious Diseases (NIAID)|
|Study Sponsor ICMJE||National Institute of Allergy and Infectious Diseases (NIAID)|
|Collaborators ICMJE||Not Provided|
|PRS Account||National Institute of Allergy and Infectious Diseases (NIAID)|
|Verification Date||January 2013|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP