Lupus Erythematosus, SystemicPhase 1SLENCT00325741
Allogeneic Blood Stem Cell Transplantation for Patients With Life-Threatening Systemic Lupus Erythematosus
A Phase 1 study testing Hematopoietic Cell Transplantation in people with Lupus Erythematosus, Systemic, run by Stanford University at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Lupus Erythematosus, Systemic
- What is being tested?
- Hematopoietic Cell Transplantation
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2004to Oct 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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:
- 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
- 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
- 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
Show all 12Show fewer
- 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:
- 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
- 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
Who cannot join
- Allergic to rabbit ATG
- Score of less than 60% on Karnofsky Performance Scale
- Organ dysfunction, defined as follows:
- 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)
- Pulmonary diffusion capacity (DLCO) less than 30% of predicted
- 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
- Measured creatinine clearance of less than 40 ml/min (24 hour urine collection)
- Pregnant
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University School of Medicine
Stanford, California, 94305
About this study
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
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.
Read the detailed description
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.
- Conditions
- Lupus Erythematosus, Systemic
- Being tested
- Hematopoietic Cell Transplantation
- Keywords
- Lupus, Systemic Lupus Erythematosus, Blood Stem Cell Transplantation
- Medical subject headings
- Lupus Erythematosus, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hematopoietic Cell TransplantationDrug
Also called NCT00325741
1200 cGy total lymphoid irradiation (TLI) are administered on day -11 through -7 and days -4 through -1 pretransplantation; rabbit ATG at 1.5 mg/kg i.v. on days -11 through -7 pretransplantation; one single infusion of donor CD34+ cells plus selected T cell add back on completion of TLI (day 0); mycophenolate mofetil (MMF) is begun on day 0 at a dose of 15 mg/kg bid and stopped on day +28; cyclosporine (CSP) at initial dose of 6.25 mg/kg and adjusted to maintain trough blood levels of 350-500 ng/ml is begun on day -3 to complete withdrawal by 6 months post-transplantation.
| Study group | Role | What they receive |
|---|---|---|
| Hematopoietc Stem Cell Transplant | Experimental | Hematopoietic Cell Transplantation. Total body irradiation and Stem cell infusion in life threating lupus patients Receives: Drug: Hematopoietic Cell Transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to achieve complete remission (participants that are off all immunosuppressive therapy without clinical or laboratory evidence of active disease)
Measured: Measured within the first year
Secondary outcomes (2)
Percentage of patients with stable chimerism in all blood and immune cell lineages
Measured: Measured within the first year
Percentage of participants with acute or chronic graft-versus-host disease
Measured: Measured within the first year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2006 (estimated)
- Study startJun 2004
- Primary completionOct 2015
- Study completionOct 2015
Why it stopped: Difficulty with recruiting participants
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lupus Erythematosus, SystemicStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), City of Hope National Medical Center
- Responsible party
- Sponsor
- Investigators
- Judith A. Shizuru, MD, PhD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00325741
- Sponsor's protocol ID
- 368
- Other IDs
- P01HL075462-02
- Acronym
- SLE
- Status last verified
- Aug 2023
- First submitted
- 12 May 2006
- Last updated
- 15 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00325741
- Acronym / sponsor ID
- SLE / 368
- Conditions
- Lupus Erythematosus, Systemic
- Keywords
- Lupus, Systemic Lupus Erythematosus, Blood Stem Cell Transplantation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulty with recruiting participants
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), City of Hope National Medical Center
- Study start
- Jun 2004 (actual)
- Primary completion
- Oct 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 15 May 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hematopoietc Stem Cell Transplant | Experimental | Drug: Hematopoietic Cell TransplantationHematopoietic Cell Transplantation. Total body irradiation and Stem cell infusion in life threating lupus patients |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- 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:
- Refractory disease, as determined by failure of the following two conditions:
- Must have a fully HLA identical sibling or a matched unrelated donor
Key exclusion criteria (8 listed)
- Allergic to rabbit ATG
- Score of less than 60% on Karnofsky Performance Scale
- Organ dysfunction, defined as follows:
- Pregnant
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hematopoietic Cell TransplantationAlso: NCT003257411200 cGy total lymphoid irradiation (TLI) are administered on day -11 through -7 and days -4 through -1 pretransplantation; rabbit ATG at 1.5 mg/kg i.v. on days -11 through -7 pretransplantation; one single infusion of donor CD34+ cells plus selected T cell add back on completion of TLI (day 0); mycophenolate mofetil (MMF) is begun on day 0 at a dose of 15 mg/kg bid and stopped on day +28; cyclosporine (CSP) at initial dose of 6.25 mg/kg and adjusted to maintain trough blood levels of 350-500 ng/ml is begun on day -3 to complete withdrawal by 6 months post-transplantation. | Drug | Hematopoietc Stem Cell Transplant |
Primary outcome
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
2 secondary outcomes
Percentage of patients with stable chimerism in all blood and immune cell lineages
Time frame: Measured within the first year
Percentage of participants with acute or chronic graft-versus-host disease
Time frame: Measured within the first year
Results and safety
The study was stopped early (reason given: Difficulty with recruiting participants). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2023.
- Individual participant dataSharing planned: No
Related trials for Lupus Erythematosus, Systemic
Not yet recruitingPhase 1
An Ascending Dose Study of DKB903 in Participants With Rheumatoid Arthritis (RA) and Participants With Systemic Lupus Erythematosus (SLE)
Rheumatoid Arthritis and Systemic Lupus Erythematosus
RecruitingPhase 4
Dapagliflozin in Active Lupus Nephritis
Lupus Nephritis (LN)
RecruitingObservational study
Electroencephalogram Recording in Patients With Systemic Lupus Erythematosus
Systemic Lupus Erythematosus
RecruitingObservational study
Deciphering the Genetic Architecture of Autoimmune Diseases
Autoimmune Diseases
RecruitingPhase 1
A Trial in Healthy Adult Participants and Adults With Autoimmune Diseases to Test How HBM7020 is Tolerated and How it Behaves in the Body
Rheumatoid Arthritis, Systemic Lupus Erythematosus
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Judith A. Shizuru, MD, PhD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Hematopoietic Cell Transplantation in people with Lupus Erythematosus, Systemic, run by Stanford University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Difficulty with recruiting participants). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2023.