Ignite Creation Date:
2024-05-05 @ 12:05 PM
Last Modification Date:
2024-10-26 @ 9:19 AM
Study NCT ID:
NCT00230035
Status:
WITHDRAWN
Last Update Posted:
2013-02-01
First Post:
2005-09-28
Brief Title:
Lupus ImmunosuppressiveImmunomodulatory Therapy or Stem Cell Transplant LIST
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institute of Allergy and Infectious Diseases NIAID
Study Overview
Official Title:
A Randomized Open Label Phase II Multicenter Study of Non-Myeloablative Autologous Transplantation With Auto-CD34HPC Versus Currently Available ImmunosuppressiveImmunomodulatory Therapy for Treatment of Systemic Lupus Erythematosus
Status:
WITHDRAWN
Status Verified Date:
2013-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Recommended by DSMB due to lack of accrual
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Systemic lupus erythematosus also known as lupus or SLE is a chronic multisystem autoimmune disease in which the bodys 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 immunosuppressiveimmunomodulatory 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 immunosuppressiveimmunomodulatory 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 immunosuppressiveimmunomodulatory therapies
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 immunosuppressiveimmunomodulatory 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 immunosuppressiveimmunomodulatory 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 immunosuppressiveimmunomodulatory therapies
Detailed Description:
SLE is a chronic multisystem inflammatory autoimmune disease in which the bodys 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 immunosuppressiveimmunomodulatory therapies
1 One group of study participants will undergo autologous hematopoietic stem cell transplantation With this treatment they will first undergo mobilization a process that removes hematopoietic stem cells from their blood Then they will receive high doses of chemotherapy to suppress their abnormal immune systems followed by the reintroduction of the purified stem cells to re-establish their immune systems
Medications are used to mobilize ie encourage blood cell precursors to multiply and move from the bone marrow to the bloodstream These precursors or autologous stem cells can be harvested collected from the bloodstream during a process called apheresis and then transplanted infused back into the patients body after chemotherapy has been given HDIT can suppress the immune system reducing the effectiveness or perhaps eliminating most of the immune cells that cause the progression of SLE Autologous hematopoietic stem cell transplantation HSCT following HDIT hastens the return of the bodys ability to produce blood cells HDIT with HSCT has been identified as a potential treatment alternative to standard chemotherapy treatments
One group of study participants will undergo autologous hematopoietic stem cell transplantation With this treatment they will first undergo mobilization a process that removes hematopoietic stem cells from their blood Then they will receive high doses of chemotherapy to suppress their abnormal immune systems followed by the reintroduction of the purified stem cells to re-establish their immune systems
Medications are used to mobilize ie encourage blood cell precursors to multiply and move from the bone marrow to the bloodstream These precursors or autologous stem cells can be harvested collected from the bloodstream during a process called apheresis and then transplanted infused back into the patients body after chemotherapy has been given HDIT can suppress the immune system reducing the effectiveness or perhaps eliminating most of the immune cells that cause the progression of SLE Autologous hematopoietic stem cell transplantation HSCT following HDIT hastens the return of the bodys ability to produce blood cells HDIT with HSCT has been identified as a potential treatment alternative to standard chemotherapy treatments
Participants assigned to the first treatment group will undergo mobilization with CTX and granulocyte colony stimulating factor G-CSF beginning 2 weeks after randomization In preparation for the transplant process a central venous line plastic tube will be inserted into the neck or chest vein this tube will be used to administer stem cells and medications and for drawing blood IV CTX followed by G-CSF will be given injected under the skin beginning 3 days after CTX G-CSF will be given for about 4 to 7 days to boost the bodys production of blood precursor cells These precursor cells will be collected through the central venous line through apheresis In this process whole blood is collected through a needle in an arm vein and directed to a cell-separating machine where the white cells are separated and saved The rest of the blood is returned to the patient through the same needle Several apheresis procedures will be required to collect enough cells for the autologous transplant
Within 3 weeks of the apheresis stem cell collection the first groups participants will be admitted to the hospital and will undergo a five-day conditioning regimen consisting of IV CTX and rabbit anti-thymocyte globulin rATG This regimen will suppress the malfunctioning immune system and prepare the patients body to receive the precursor cells previously collected during apheresis The stem cells will be infused after the five-day conditioning regimen The return of the precursor cells is called autologous stem cell transplantation During the hospitalization a specialized team of transplant physicians and nurses will closely monitor the participants until their bone marrow recovers and the participants are well enough to be discharged The hospital stay will be approximately 21 days after the autologous stem cell transplant Upon discharge the patient will return home and will follow-up at the treatment center at Weeks 1 and 3 post-transplantation for close monitoring by the transplant team Participants will also be followed by the study rheumatologist monthly at the treatment center for 30 months
2 The other group of study participants will receive immunosuppressiveimmunomodulatory therapy as prescribed by the study rheumatologist based on the organ systems affected and prior treatment history Therapy may include one or a combination of the following treatments corticosteroids azathioprine methotrexate cyclosporine MMF plasmapheresis IVIG rituximab and leflunomide As new drugs become available and a part of the usual medications for the treatment of SLE they may be approved for use in this study Treatment may be changed as frequently as necessary within the first year of the study to control the manifestations of SLE in each patient Treatment for the second group will begin 1 week after randomization patients will be seen monthly at the treatment center for 30 months
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 mgday 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 individuals 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 studys 5-year duration Participants will be contacted via telephone e-mail or visit every 3 months to assess their use of concomitant medications and immunosuppressiveimmunomodulatory 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
1 One group of study participants will undergo autologous hematopoietic stem cell transplantation With this treatment they will first undergo mobilization a process that removes hematopoietic stem cells from their blood Then they will receive high doses of chemotherapy to suppress their abnormal immune systems followed by the reintroduction of the purified stem cells to re-establish their immune systems
Medications are used to mobilize ie encourage blood cell precursors to multiply and move from the bone marrow to the bloodstream These precursors or autologous stem cells can be harvested collected from the bloodstream during a process called apheresis and then transplanted infused back into the patients body after chemotherapy has been given HDIT can suppress the immune system reducing the effectiveness or perhaps eliminating most of the immune cells that cause the progression of SLE Autologous hematopoietic stem cell transplantation HSCT following HDIT hastens the return of the bodys ability to produce blood cells HDIT with HSCT has been identified as a potential treatment alternative to standard chemotherapy treatments
One group of study participants will undergo autologous hematopoietic stem cell transplantation With this treatment they will first undergo mobilization a process that removes hematopoietic stem cells from their blood Then they will receive high doses of chemotherapy to suppress their abnormal immune systems followed by the reintroduction of the purified stem cells to re-establish their immune systems
Medications are used to mobilize ie encourage blood cell precursors to multiply and move from the bone marrow to the bloodstream These precursors or autologous stem cells can be harvested collected from the bloodstream during a process called apheresis and then transplanted infused back into the patients body after chemotherapy has been given HDIT can suppress the immune system reducing the effectiveness or perhaps eliminating most of the immune cells that cause the progression of SLE Autologous hematopoietic stem cell transplantation HSCT following HDIT hastens the return of the bodys ability to produce blood cells HDIT with HSCT has been identified as a potential treatment alternative to standard chemotherapy treatments
Participants assigned to the first treatment group will undergo mobilization with CTX and granulocyte colony stimulating factor G-CSF beginning 2 weeks after randomization In preparation for the transplant process a central venous line plastic tube will be inserted into the neck or chest vein this tube will be used to administer stem cells and medications and for drawing blood IV CTX followed by G-CSF will be given injected under the skin beginning 3 days after CTX G-CSF will be given for about 4 to 7 days to boost the bodys production of blood precursor cells These precursor cells will be collected through the central venous line through apheresis In this process whole blood is collected through a needle in an arm vein and directed to a cell-separating machine where the white cells are separated and saved The rest of the blood is returned to the patient through the same needle Several apheresis procedures will be required to collect enough cells for the autologous transplant
Within 3 weeks of the apheresis stem cell collection the first groups participants will be admitted to the hospital and will undergo a five-day conditioning regimen consisting of IV CTX and rabbit anti-thymocyte globulin rATG This regimen will suppress the malfunctioning immune system and prepare the patients body to receive the precursor cells previously collected during apheresis The stem cells will be infused after the five-day conditioning regimen The return of the precursor cells is called autologous stem cell transplantation During the hospitalization a specialized team of transplant physicians and nurses will closely monitor the participants until their bone marrow recovers and the participants are well enough to be discharged The hospital stay will be approximately 21 days after the autologous stem cell transplant Upon discharge the patient will return home and will follow-up at the treatment center at Weeks 1 and 3 post-transplantation for close monitoring by the transplant team Participants will also be followed by the study rheumatologist monthly at the treatment center for 30 months
2 The other group of study participants will receive immunosuppressiveimmunomodulatory therapy as prescribed by the study rheumatologist based on the organ systems affected and prior treatment history Therapy may include one or a combination of the following treatments corticosteroids azathioprine methotrexate cyclosporine MMF plasmapheresis IVIG rituximab and leflunomide As new drugs become available and a part of the usual medications for the treatment of SLE they may be approved for use in this study Treatment may be changed as frequently as necessary within the first year of the study to control the manifestations of SLE in each patient Treatment for the second group will begin 1 week after randomization patients will be seen monthly at the treatment center for 30 months
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 mgday 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 individuals 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 studys 5-year duration Participants will be contacted via telephone e-mail or visit every 3 months to assess their use of concomitant medications and immunosuppressiveimmunomodulatory 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None