Systemic Lupus ErythematosusPhase 1NCT00849745
Nonmyeloablative Allo Stem Cell Transplant for Severe Autoimmune Diseases
A Phase 1 study testing Nonmyeloablative allogeneic stem cell transplant in people with Systemic Lupus Erythematosus and Systemic Sclerosis, run by Duke University at 1 site in United States.
Trial summary
Autoimmune diseases present a special challenge to clinicians and the aim of this protocol is to serve as a last-line effort for patients with unmanageable disease. The primary purpose of this study is to assess feasibility in terms of toxicity and engraftment of a less toxic, nonablative conditioning regimen of… Read more about this study
- Who is it for?
- Ages 18 to 69 years
- Conditions the study is for
- Systemic Lupus Erythematosus, Systemic Sclerosis
- What is being tested?
- Nonmyeloablative allogeneic stem cell transplant
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2003to Jul 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 69 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Pregnant or lactating women
- Active uncontrolled infection
- Patients who are serologically true-positive for HIV
- Patients with other major medical or psychiatric illnesses, which the treating physician feels, could seriously compromise tolerance to this protocol
- Uncontrolled hypertension (BP > 100 diastolic despite treatment with maximum doses of at least 3 simultaneous or concurrent antihypertensives over a 2-month period)
- Uncontrolled malignant arrythmias or clinical evidence of congestive heart failure (New York Class IV)
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- 6/6 HLA-Matched Related PBSC Donor Inclusion/Exclusion Criteria:
- Adult donors must be capable of providing informed consent; Potential donors under the age of 18 must have a 'single patient exemption' approved by the IRB and the donor and a guardian must provide assent.
- Donor must be 6/6 HLA matched, and related to the patient.
- Donor must not have any medical condition which would make apheresis and G-CSF administration more than a minimal risk, and should have the following:
- Adequate cardiac function by history and physical examination. Those with a history of cardiac problems should undergo a stress evaluation or be evaluated by a cardiologist and deemed eligible to donate.
- bilirubin and hepatic transaminases < or equal to 2.5 x ULN,
- adequate hematologic parameters including a hematocrit > 35% for males and 33% for females, white blood cell count of > or equal to 3,000, and platelets > or equal to 80,000.
- Donors with a known allergy to E. coli-derived products are ineligible for mobilization with G-CSF.
- Females of childbearing potential should have a negative serum beta-HCG test within 1 week of beginning G-CSF.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Health System
Durham, North Carolina, 27705
About this study
Official title: Nonmyeloablative Allogeneic Peripheral Blood Stem Cell Transplantation for Severe Autoimmune Diseases
Autoimmune diseases present a special challenge to clinicians and the aim of this protocol is to serve as a last-line effort for patients with unmanageable disease. The primary purpose of this study is to assess feasibility in terms of toxicity and engraftment of a less toxic, nonablative conditioning regimen of Campath-1H, moderate dose fludarabine, and cyclophosphamide for patients with severe autoimmune diseases.
Read the detailed description
Our targeted illnesses are:
- Systemic lupus erythematosus (SLE): SLE can involve virtually any organ system, but most commonly involves various combinations of arthritis, dermatitis, glomerulonephritis, central nervous system manifestations and hematologic complications. Although the overall five and ten-year survival rates in SLE are 86% and 80%, respectively, these rates are reduced to 60% and 50%, respectively, in patients with poor prognosis SLE (proliferative glomerulonephritis with chronic changes, elevated serum creatinine, nephrotic syndrome, anemia, low serum C3, inadequate response to treatment).
- Systemic sclerosis (SSc): SSc is a condition divided into two forms (diffuse and limited) characterized by excessive and often relentless fibrosis in skin and internal organs. Visceral involvement can manifest as esophageal hypomotility, interstitial lung disease, pulmonary hypertension and renal failure. There is no satisfactory treatment for systemic sclerosis (SSc), which in its diffuse form has a 5-year mortality of 40%, similar to many malignancies. In clinical trials, alpha-interferon did not demonstrate a clinically significant effect and low dose methotrexate showed conflicting results.
- Conditions
- Systemic Lupus Erythematosus, Systemic Sclerosis
- Being tested
- Nonmyeloablative allogeneic stem cell transplant
- Keywords
- severe autoimmune diseases, allogeneic stem cell transplant
- Medical subject headings
- Lupus Erythematosus, Systemic, Scleroderma, Systemic, Autoimmune Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nonmyeloablative allogeneic stem cell transplantProcedure or surgery
Also called Campath-1H
Prior to receiving Campath-1H, patients will be premedicated with Benadryl 50 mg IV or PO, and acetaminophen 650 mg orally. Hydrocortisone 100 mg IV is given on the first day of Campath. The preparative regimen will begin on day -5 and consist of 4 days of daily fludarabine at 30 mg/m2/d infused over 30 minutes, cyclophosphamide 500 mg/m2/d infused over 1 hour, 5 days of Campath-1H at 20 mg/d in 250 ml of D5 normal saline or normal saline infused over 3 hours. The mixed dosage of chemotherapy may be rounded off to within +/- 5% of the calculated dose, and doses of fludarabine and cyclophosphamide will be based on adjusted ideal body weight. IV hydration and diuretics will be used to maintain adequate urine output during and after administration of cyclophosphamide.
| Study group | Role | What they receive |
|---|---|---|
| Systemic Lupus Erythematosus | Experimental | Nonmyeloablative allogeneic stem cell transplant
Patients must:
* Satisfy the American College of Rheumatology (ACR) criteria for the diagnosis of SLE
* Have Lupus nephritis, refractory and severe seizures or encephalopathy, severe pulmonary involvement, transfusion-dependent cytopenias, catastrophic antiphospholipid syndrome or vasculitis and/or immune complex deposition causing end-organ signs or symptoms.
* Have received a trial of corticosteroids equivalent to prednisone greater than or equal to 0.5 mg/kg/d for at least one month
* Have received a trial of IV cyclophosphamide pulse greater than 500 mg/square meter at least once within the previous 6 months, unless contraindicated because of severe cytopenias or intolerance. Receives: Procedure: Nonmyeloablative allogeneic stem cell transplant |
| Systemic Sclerosis | Experimental | Nonmyeloablative allogeneic stem cell transplant
Patients must:
* Have diagnosis of SSc as defined by American College of Rheumatology and at high-risk for fatal outcome.
* Have (1) both a and b below and (2) at least one of c, d, or e.
* Diffuse cutaneous scleroderma with skin score of >= 16
* Duration of systemic sclerosis <= 3 years from the onset of first non-Raynaud's symptom.
* Presence of interstitial or pulmonary vascular lung involvement (FVC or DLCO <70% of predicted) especially with evidence of alveolitis (abnormal bronchoalveolar lavage or high-resolution chest CT scan).
* Presence of myocardial disease
* History or presence of proteinuria > 500 mg/24 hrs or serum creatinine > the upper limit of normal. Receives: Procedure: Nonmyeloablative allogeneic stem cell transplant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Engraftment
Measured: 24 months
Graft versus Host Disease
Measured: 45 days
Toxicity
Occurrence of Grade 3-4 adverse events
Measured: 45 days
Mortality
Occurrence of deaths
Measured: 24 months
Secondary outcomes (4)
Response Rate
Measured: 24 months
Immune Function Post-engraftment
Measured: 24 months
Progression Free Survival
Measured: 24 months
Overall Survival
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2009 (estimated)
- Study startJan 2003
- Primary completionJul 2015
- Study completionJul 2015
Why it stopped: low accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Systemic Lupus ErythematosusStudies of the same condition, open and under way.
- More trials run by Duke 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Keith Sullivan, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00849745
- Sponsor's protocol ID
- Pro00010324
- Status last verified
- Jun 2016
- First submitted
- 22 Feb 2009
- Last updated
- 23 Jun 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nonmyeloablative Allogeneic Peripheral Blood Stem Cell Transplantation for Severe Autoimmune Diseases
- ClinicalTrials.gov ID
- NCT00849745
- Acronym / sponsor ID
- Pro00010324
- Conditions
- Systemic Lupus Erythematosus, Systemic Sclerosis
- Keywords
- severe autoimmune diseases, allogeneic stem cell transplant
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: low accrual
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Study start
- Jan 2003
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 24 Feb 2009 (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.
Autoimmune diseases present a special challenge to clinicians and the aim of this protocol is to serve as a last-line effort for patients with unmanageable disease. The primary purpose of this study is to assess feasibility in terms of toxicity and engraftment of a less toxic, nonablative conditioning regimen of Campath-1H, moderate dose fludarabine, and cyclophosphamide for patients with severe autoimmune diseases.
Detailed description
Our targeted illnesses are:
- Systemic lupus erythematosus (SLE): SLE can involve virtually any organ system, but most commonly involves various combinations of arthritis, dermatitis, glomerulonephritis, central nervous system manifestations and hematologic complications. Although the overall five and ten-year survival rates in SLE are 86% and 80%, respectively, these rates are reduced to 60% and 50%, respectively, in patients with poor prognosis SLE (proliferative glomerulonephritis with chronic changes, elevated serum creatinine, nephrotic syndrome, anemia, low serum C3, inadequate response to treatment).
- Systemic sclerosis (SSc): SSc is a condition divided into two forms (diffuse and limited) characterized by excessive and often relentless fibrosis in skin and internal organs. Visceral involvement can manifest as esophageal hypomotility, interstitial lung disease, pulmonary hypertension and renal failure. There is no satisfactory treatment for systemic sclerosis (SSc), which in its diffuse form has a 5-year mortality of 40%, similar to many malignancies. In clinical trials, alpha-interferon did not demonstrate a clinically significant effect and low dose methotrexate showed conflicting results.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Systemic Lupus Erythematosus | Experimental | Procedure: Nonmyeloablative allogeneic stem cell transplantNonmyeloablative allogeneic stem cell transplant Patients must: * Satisfy the American College of Rheumatology (ACR) criteria for the diagnosis of SLE * Have Lupus nephritis, refractory and severe seizures or encephalopathy, severe pulmonary involvement, transfusion-dependent cytopenias, catastrophic antiphospholipid syndrome or vasculitis and/or immune complex deposition causing end-organ signs or symptoms. * Have received a trial of corticosteroids equivalent to prednisone greater than or equal to 0.5 mg/kg/d for at least one month * Have received a trial of IV cyclophosphamide pulse greater than 500 mg/square meter at least once within the previous 6 months, unless contraindicated because of severe cytopenias or intolerance. |
| Systemic Sclerosis | Experimental | Procedure: Nonmyeloablative allogeneic stem cell transplantNonmyeloablative allogeneic stem cell transplant Patients must: * Have diagnosis of SSc as defined by American College of Rheumatology and at high-risk for fatal outcome. * Have (1) both a and b below and (2) at least one of c, d, or e. * Diffuse cutaneous scleroderma with skin score of >= 16 * Duration of systemic sclerosis <= 3 years from the onset of first non-Raynaud's symptom. * Presence of interstitial or pulmonary vascular lung involvement (FVC or DLCO <70% of predicted) especially with evidence of alveolitis (abnormal bronchoalveolar lavage or high-resolution chest CT scan). * Presence of myocardial disease * History or presence of proteinuria > 500 mg/24 hrs or serum creatinine > the upper limit of normal. |
Who may qualify
- Ages
- 18 to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (15 listed)
- Pregnant or lactating women
- Active uncontrolled infection
- Patients who are serologically true-positive for HIV
- Patients with other major medical or psychiatric illnesses, which the treating physician feels, could seriously compromise tolerance to this protocol
- Uncontrolled hypertension (BP > 100 diastolic despite treatment with maximum doses of at least 3 simultaneous or concurrent antihypertensives over a 2-month period)
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 |
|---|---|---|
| Nonmyeloablative allogeneic stem cell transplantAlso: Campath-1HPrior to receiving Campath-1H, patients will be premedicated with Benadryl 50 mg IV or PO, and acetaminophen 650 mg orally. Hydrocortisone 100 mg IV is given on the first day of Campath. The preparative regimen will begin on day -5 and consist of 4 days of daily fludarabine at 30 mg/m2/d infused over 30 minutes, cyclophosphamide 500 mg/m2/d infused over 1 hour, 5 days of Campath-1H at 20 mg/d in 250 ml of D5 normal saline or normal saline infused over 3 hours. The mixed dosage of chemotherapy may be rounded off to within +/- 5% of the calculated dose, and doses of fludarabine and cyclophosphamide will be based on adjusted ideal body weight. IV hydration and diuretics will be used to maintain adequate urine output during and after administration of cyclophosphamide. | Procedure or surgery | Systemic Lupus Erythematosus, Systemic Sclerosis |
Primary outcome
Engraftment
Time frame: 24 months
Graft versus Host Disease
Time frame: 45 days
Toxicity
Time frame: 45 days
Occurrence of Grade 3-4 adverse events
Mortality
Time frame: 24 months
Occurrence of deaths
4 secondary outcomes
Response Rate
Time frame: 24 months
Immune Function Post-engraftment
Time frame: 24 months
Progression Free Survival
Time frame: 24 months
Overall Survival
Time frame: 24 months
Results and safety
The study was stopped early (reason given: low accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2016.
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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.
Keith Sullivan, MD principal investigator
Duke 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 Nonmyeloablative allogeneic stem cell transplant in people with Systemic Lupus Erythematosus and Systemic Sclerosis, run by Duke 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 0 inclusion and 15 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 23 Jun 2016. 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: low accrual). 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?
Engraftment (time frame: 24 months). The study lists 4 primary outcomes in all. 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 23 Jun 2016.