SYSTEMIC SCLERODERMAPhase 2NCT00278525
Cyclophosphamide and rATG With Hematopoietic Stem Cell Support in Systemic Scleroderma
A Phase 2 study testing stem cell transplantation in people with SYSTEMIC SCLERODERMA, run by Northwestern University at 1 site in United States.
Trial summary
Scleroderma is a systemic disorder categorized as an immunologically mediated disease that causes collagen deposition of skin and visceral organs. The molecular pathogenesis of scleroderma has been elusive, although vasculopathy and immune mediated mechanisms are thought to be important. Read more about this study
- Who is it for?
- Ages Up to 60 years
- Conditions the study is for
- SYSTEMIC SCLERODERMA
- What is being tested?
- stem cell transplantation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2005to Dec 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 Up to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age 60 year or < 60 year old at the time of pretransplant evaluation.
- An established diagnosis of scleroderma.
- Diffuse cutaneous scleroderma with involvement proximal to the elbow or knee and a Rodnan score of > 14
- AND
- Scleroderma with any one of the following:
- Diffusing capacity of the lung for carbon monoxide (DLCO) < 80% of predicted or decrease in lung function [DLCO, diffusing capacity divided by the alveolar volume (DLCO/VA) or forced vital capacity (FVC) ] of 10% or more over 12 months.
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- Active alveolitis on bronchoalveolar lavage.
- Pulmonary fibrosis or alveolitis on computed tomography (CT) scan or chest x-ray (CXR) (ground glass appearance of alveolitis).
- Renal disease that is not explained by a bacterial infection or other renal disorders. (Subjects must have two or more of the following: proteinuria - greater than trace on dipstick, hematuria - urine blood on dipstick or sediment, hypertension that requires treatment with anti-hypertensive medications or untreated but with a diastolic blood pressure (BP) > 95 mm/hg.)
- Abnormal electrocardiogram (EKG) (non-specific ST-T wave abnormalities, low QRS voltage, or ventricular hypertrophy), or pericardial effusion or pericardial enhancement on magnetic resonance imaging (MRI)
- Gastrointestinal tract involvement confirmed on radiological study. Radiologic findings of scleroderma are small bowel radiographs showing thickened folds with dilated loops, segmentation, and flocculation +/- diverticulae, or pseudodiverticulae. A hide-bound appearance due to valvulae packing i.e. dilated and crowded circular folds, may be present. Gastrointestinal (GI) involvement may also be confirmed by D-xylose malabsorption, patulous esophagus, or esophageal manometry.
- OR
- As published in NEJM, 2006, 345:25 2655-2709. Limited or diffuse SSL with lung involvement defined as active alveolitis on bronchoalveolar lavage (BAL) or ground-glass opacity on CT, a DLCO < 80% predicted or decrease in lung function (DLCO/VA,DLCO, FVC) of 10% or more in last 12 months.
Who cannot join
- Poor performance status Eastern Cooperative Oncology Group (ECOG 2) at the time of entry.
- Significant end organ damage such as:
- Left Ventricular Ejection Fraction (LVEF) < 40% or deterioration of LVEF during exercise test on Multiple Gated Acquisition (MUGA) or echocardiogram.
- Untreated life-threatening arrhythmia.
- Active ischemic heart disease or heart failure.
- End-stage lung disease characterized by total lung capacity (TLC) <45% of predicted value.
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- Pulmonary hypertension (systolic pulmonary arterial pressure > 40 mmHg or mean pulmonary arterial pressure (PAP) > 25 mmHG measurement by pulmonary arterial catheter).
- Serum creatinine > 2.0 mg/dl.
- Liver cirrhosis, transaminases > 3x of normal limits or bilirubin > 2.0 unless due to Gilberts disease.
- Pericardial effusion> 200ml unless successful pericardiocentesis
- Tricuspid annular peak systolic excursion (TAPSE) ≤ 1.9 cm
- MRI of heart showing D sign (intraventricular flattering)
- Human immunodeficiency virus (HIV) positive.
- Uncontrolled diabetes mellitus, or any other illness that in the opinion of the investigators would jeopardize the ability of the patient to tolerate aggressive treatment.
- Prior history of malignancy except localized basal cell or squamous skin cancer. Other malignancies for which the patient is judged to be cured by local surgical therapy, such as (but not limited to) head and neck cancer, or stage I or II breast cancer will be considered on an individual basis.
- Positive pregnancy test, inability or unable to pursue effective means of birth control, failure to willingly accept or comprehend irreversible sterility as a side effect of therapy.
- Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible.
- Inability to give informed consent.
- Major hematological abnormalities such as platelet count < 100,000/ul or absolute neutrophil count (ANC) < 1000/ul.
- Patients with duration of disease > 5 years.
- Exclude if > than 6 prior monthly IV cyclophosphamide treatments.
Trial locations and contacts
1 site in 1 country.
United States1 site
Northwestern University, Feinberg School of Medicine
Chicago, Illinois, 60611
About this study
Official title: Trial of High Dose Cyclophosphamide and Rabbit Antithymocyte Globulin (rATG) With Hematopoietic Stem Cell Support in Patients With Systemic Scleroderma: A Randomized Trial
Scleroderma is a systemic disorder categorized as an immunologically mediated disease that causes collagen deposition of skin and visceral organs. The molecular pathogenesis of scleroderma has been elusive, although vasculopathy and immune mediated mechanisms are thought to be important. Once extensive cutaneous or visceral disease occurs, prognosis is significantly shorter than the general population. Although various treatments have been tried, none of them seems to have changed the natural history of scleroderma. Standard dose immunosuppressive treatment has been disappointing. Recently, cyclophosphamide at 1-2 mg/kg/day orally or 800-1400 mg intravenous (IV) monthly for 6-9 months has proven effective in treatment of scleroderma alveolitis (1). Recent phase I studies of immunoablation with autologous peripheral blood stem cell transplantation (PBSCT) showed some promising data, but the exact efficacy is undetermined (2,3). We now propose, as a phase II randomized study, autologous unmanipulated PBSCT versus pulse cyclophosphamide in patients with systemic scleroderma.
Read the detailed description
To evaluate the efficacy of two treatment modalities: pulse cyclophosphamide versus high dose cyclophosphamide and anti-thymocyte globulin (ATG) rescued with autologous peripheral blood stem cell transplantation (PBSCT). The primary endpoints to be considered in this study are:
I)Time to Treatment Failure -Treatment failure will not occur until a minimum of 12 months after enrollment at which time failure is defined as:
- Failure of skin score (if > 14 on enrollment) to improve or increase in skin score by a 25% above lowest post treatment value and must be documented on 2 occasion 6 months apart
- Deterioration in diffusing capacity of the lung for carbon monoxide (DLCO), diffusing capacity divided by the alveolar volume (DLCO/VA) or forced vital capacity (FVC) by 10% below enrollment level or 10% below best post treatment value, due to systemic sclerosis, and documented on 2 occasion 6 months apart
- Renal failure due to systemic sclerosis and defined as chronic dialysis for more than 12 months
- Gastrointestinal failure due to systemic sclerosis and defined as initiation of total parenteral nutrition (TPN) for more than 12 months
II) Disease improvement defined by at least 25% improvement in skin score (Rodnan), or 10% improvement in pulmonary function tests (DLCO, DLCO/VA, or FVC), or in cardiac tests [pulmonary artery (PA) systolic pressure by right heart cath) that persists > 6 months or ability to wean off TPN
- Conditions
- SYSTEMIC SCLERODERMA
- Being tested
- standard of care, stem cell transplantation
- Medical subject headings
- Scleroderma, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
standard of careDrug
standard of care medication will be given
stem cell transplantationProcedure or surgery
Also called stem cell transplant, stem cell injection
The following is intervention: stem cell transplantation after conditioning regimen
| Study group | Role | What they receive |
|---|---|---|
| stem cell trasplantation | Experimental | intervention as stem cell transplantation after conditioning regimen Receives: Procedure: stem cell transplantation |
| standard of care | Active comparator | medication as standard of care will be given Receives: Drug: standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Treatment Failure
-Data are reporting number of participants that were classified as treatment failures
Time to Treatment Failure Definition-Treatment failure will not occur until a minimum of 12 months after enrollment at which time failure is defined as:
- Failure of skin score (if > 14 on enrollment) to improve or increase in skin score by a 25% above lowest post treatment value and must be documented on 2 occasion 6 months apart
- Deterioration in diffusing capacity of the lung for carbon monoxide (DLCO), diffusing capacity divided by the alveolar volume (DLCO/VA) or forced vital capacity (FVC) by 10% below enrollment level or 10% below best post treatment value, due to systemic sclerosis, and documented on 2 occasion 6 months apart
- Renal failure due to systemic sclerosis and defined as chronic dialysis for more than 12 months
- Gastrointestinal failure due to systemic sclerosis and defined as initiation of total parenteral nutrition(TPN) for more than 12 months
Measured: 12 months
Disease Improvement
Data are reporting number of participants that were classified as disease improvement.
Definition of disease improvement:
Disease improvement defined by at least 25% improvement in skin score (Rodnan), or 10% improvement in pulmonary function tests [diffusing capacity of the lung for carbon monoxide (DLCO), diffusing capacity divided by the alveolar volume (DLCO/VA), or forced vital capacity (FVC)], or in cardiac tests [pulmonary artery (PA) systolic pressure by right heart cath] that persists > 6 months or ability to wean off total parenteral nutrition (TPN)
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2006 (estimated)
- Study startSep 2005
- Primary completionSep 2011
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for SYSTEMIC SCLERODERMAStudies of the same condition, open and under way.
- More trials run by Northwestern 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Richard Burt, MD, Northwestern University
- Investigators
- Richard Burt, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00278525
- Sponsor's protocol ID
- DI Scl.Randomized2004
- Status last verified
- Mar 2014
- First submitted
- 15 Jan 2006
- Last updated
- 30 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Bruera S, Sidanmat H, Molony DA, Mayes MD, Suarez-Almazor ME, Krause K, Lopez-Olivo MA. Stem cell transplantation for systemic sclerosis. Cochrane Database Syst Rev. 2022 Jul 29;7(7):CD011819. doi: 10.1002/14651858.CD011819.pub2.
PubMed 35904231Burt RK, Shah SJ, Dill K, Grant T, Gheorghiade M, Schroeder J, Craig R, Hirano I, Marshall K, Ruderman E, Jovanovic B, Milanetti F, Jain S, Boyce K, Morgan A, Carr J, Barr W. Autologous non-myeloablative haemopoietic stem-cell transplantation compared with pulse cyclophosphamide once per month for systemic sclerosis (ASSIST): an open-label, randomised phase 2 trial. Lancet. 2011 Aug 6;378(9790):498-506. doi: 10.1016/S0140-6736(11)60982-3. Epub 2011 Jul 21.
PubMed 21777972
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Trial of High Dose Cyclophosphamide and Rabbit Antithymocyte Globulin (rATG) With Hematopoietic Stem Cell Support in Patients With Systemic Scleroderma: A Randomized Trial
- ClinicalTrials.gov ID
- NCT00278525
- Acronym / sponsor ID
- DI Scl.Randomized2004
- Conditions
- SYSTEMIC SCLERODERMA
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Study start
- Sep 2005
- Primary completion
- Sep 2011 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 18 Jan 2006 (estimated)
- Results
- Posted 30 Apr 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Scleroderma is a systemic disorder categorized as an immunologically mediated disease that causes collagen deposition of skin and visceral organs. The molecular pathogenesis of scleroderma has been elusive, although vasculopathy and immune mediated mechanisms are thought to be important. Once extensive cutaneous or visceral disease occurs, prognosis is significantly shorter than the general population. Although various treatments have been tried, none of them seems to have changed the natural history of scleroderma. Standard dose immunosuppressive treatment has been disappointing. Recently, cyclophosphamide at 1-2 mg/kg/day orally or 800-1400 mg intravenous (IV) monthly for 6-9 months has proven effective in treatment of scleroderma alveolitis (1). Recent phase I studies of immunoablation with autologous peripheral blood stem cell transplantation (PBSCT) showed some promising data, but the exact efficacy is undetermined (2,3). We now propose, as a phase II randomized study, autologous unmanipulated PBSCT versus pulse cyclophosphamide in patients with systemic scleroderma.
Detailed description
To evaluate the efficacy of two treatment modalities: pulse cyclophosphamide versus high dose cyclophosphamide and anti-thymocyte globulin (ATG) rescued with autologous peripheral blood stem cell transplantation (PBSCT). The primary endpoints to be considered in this study are:
I)Time to Treatment Failure -Treatment failure will not occur until a minimum of 12 months after enrollment at which time failure is defined as:
- Failure of skin score (if > 14 on enrollment) to improve or increase in skin score by a 25% above lowest post treatment value and must be documented on 2 occasion 6 months apart
- Deterioration in diffusing capacity of the lung for carbon monoxide (DLCO), diffusing capacity divided by the alveolar volume (DLCO/VA) or forced vital capacity (FVC) by 10% below enrollment level or 10% below best post treatment value, due to systemic sclerosis, and documented on 2 occasion 6 months apart
- Renal failure due to systemic sclerosis and defined as chronic dialysis for more than 12 months
- Gastrointestinal failure due to systemic sclerosis and defined as initiation of total parenteral nutrition (TPN) for more than 12 months
II) Disease improvement defined by at least 25% improvement in skin score (Rodnan), or 10% improvement in pulmonary function tests (DLCO, DLCO/VA, or FVC), or in cardiac tests [pulmonary artery (PA) systolic pressure by right heart cath) that persists > 6 months or ability to wean off TPN
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| stem cell trasplantation | Experimental | Procedure: stem cell transplantationintervention as stem cell transplantation after conditioning regimen |
| standard of care | Active comparator | Drug: standard of caremedication as standard of care will be given |
Who may qualify
- Ages
- Up to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (13 listed)
- Age 60 year or < 60 year old at the time of pretransplant evaluation.
- An established diagnosis of scleroderma.
- Diffuse cutaneous scleroderma with involvement proximal to the elbow or knee and a Rodnan score of > 14
- AND
- Diffusing capacity of the lung for carbon monoxide (DLCO) < 80% of predicted or decrease in lung function [DLCO, diffusing capacity divided by the alveolar volume (DLCO/VA) or forced vital capacity (FVC) ] of 10% or more over 12 months.
Key exclusion criteria (21 listed)
- Poor performance status Eastern Cooperative Oncology Group (ECOG 2) at the time of entry.
- Significant end organ damage such as:
- Human immunodeficiency virus (HIV) positive.
- Uncontrolled diabetes mellitus, or any other illness that in the opinion of the investigators would jeopardize the ability of the patient to tolerate aggressive treatment.
- Prior history of malignancy except localized basal cell or squamous skin cancer. Other malignancies for which the patient is judged to be cured by local surgical therapy, such as (but not limited to) head and neck cancer, or stage I or II breast cancer will be considered on an individual basis.
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 |
|---|---|---|
| standard of carestandard of care medication will be given | Drug | standard of care |
| stem cell transplantationAlso: stem cell transplant, stem cell injectionThe following is intervention: stem cell transplantation after conditioning regimen | Procedure or surgery | stem cell trasplantation |
Primary outcome
Time to Treatment Failure
Time frame: 12 months
-Data are reporting number of participants that were classified as treatment failures Time to Treatment Failure Definition-Treatment failure will not occur until a minimum of 12 months after enrollment at which time failure is defined as: 1. Failure of skin score (if > 14 on enrollment) to improve or increase in skin score by a 25% above lowest post treatment value and must be documented on 2 occasion 6 months apart 2. Deterioration in diffusing capacity of the lung for carbon monoxide (DLCO), diffusing capacity divided by the alveolar volume (DLCO/VA) or forced vital capacity (FVC) by 10% below enrollment level or 10% below best post treatment value, due to systemic sclerosis, and documented on 2 occasion 6 months apart 3. Renal failure due to systemic sclerosis and defined as chronic dialysis for more than 12 months 4. Gastrointestinal failure due to systemic sclerosis and defined as initiation of total parenteral nutrition(TPN) for more than 12 months
Disease Improvement
Time frame: 12 months
Data are reporting number of participants that were classified as disease improvement. Definition of disease improvement: Disease improvement defined by at least 25% improvement in skin score (Rodnan), or 10% improvement in pulmonary function tests [diffusing capacity of the lung for carbon monoxide (DLCO), diffusing capacity divided by the alveolar volume (DLCO/VA), or forced vital capacity (FVC)], or in cardiac tests [pulmonary artery (PA) systolic pressure by right heart cath] that persists > 6 months or ability to wean off total parenteral nutrition (TPN)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35904231Bruera S, Sidanmat H, Molony DA, Mayes MD, Suarez-Almazor ME, Krause K, Lopez-Olivo MA. Stem cell transplantation for systemic sclerosis. Cochrane Database Syst Rev. 2022 Jul 29;7(7):CD011819. doi: 10.1002/14651858.CD011819.pub2.
- Derived from this study: PubMed 21777972Burt RK, Shah SJ, Dill K, Grant T, Gheorghiade M, Schroeder J, Craig R, Hirano I, Marshall K, Ruderman E, Jovanovic B, Milanetti F, Jain S, Boyce K, Morgan A, Carr J, Barr W. Autologous non-myeloablative haemopoietic stem-cell transplantation compared with pulse cyclophosphamide once per month for systemic sclerosis (ASSIST): an open-label, randomised phase 2 trial. Lancet. 2011 Aug 6;378(9790):498-506. doi: 10.1016/S0140-6736(11)60982-3. Epub 2011 Jul 21.
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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.
Richard Burt, MD principal investigator
Northwestern University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing stem cell transplantation in people with SYSTEMIC SCLERODERMA, run by Northwestern 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 13 inclusion and 21 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: finished, as of the sponsor's last update on 30 Apr 2014. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 Treatment Failure (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00278525, which also lists 2 linked publications.
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 30 Apr 2014; AzTrials last refreshed its copy on 6 Nov 2026.