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Systemic SclerosisPhase 2SScNCT03630211

Autologous Stem Cell Transplantation in Patients With Systemic Sclerosis

A Phase 2 study testing Cyclophosphamide, Mesna and Rituximab in people with Systemic Sclerosis and Diffuse Sclerosis Systemic, run by Paul Szabolcs at 3 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

The purpose of this study is to determine whether a regimen of high-dose immunoablative therapy will demonstrate safety that is consistent or improved with other published regimens in SSc patients, while maintaining a treatment effect. Read more about this study

Who is it for?
Ages 8 to 60 years
What is being tested?
Cyclophosphamide, Mesna and Rituximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
3 sitesUnited States
Study dates
31 Jul 2018to 1 Aug 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 8 to 60 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Individuals must meet all the following criteria to be eligible for this study.
  • Patient, parent, or legal guardian must have given written informed consent. For patients ≥ 168 years of age who are developmentally able, assent or affirmation will be obtained.
  • Age 8-24, inclusive, at time of consent.
  • Diagnosed with Systemic Sclerosis (SSc) at the age of ≤19.
  • Failure to respond, specifically no improvement or progression of disease, to at least 2 disease-modifying antirheumatic drugs (DMARDS) within 12 months of consent with any of the following conditions:
  • Progression of skin thickening over the past 6 months or Modified Rodnan skin score (mRSS) ≥ 20
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  • Progression of ILD within 18 months prior to consent. Progression to be determined by either of the following:
  • CT scan showing increased ground glass opacities or reticulations OR
  • Pulmonary function testing (PFTs) showing a decrease in FVC% or DLCO% predicted value of ≥10%.
  • Myositis - CPK > 2x upper limit of normal or MRI consistent with myositis
  • Childhood Myositis Assessment Score < 30
  • Arthritis
  • Digital tip ulcerations
  • Cardiology clearance to undergo stem cell transplantation (documented in subject's medical chart)
  • Negative for human immunodeficiency virus (HIV), hepatitis B virus and hepatitis C virus, all confirmed by PCR testing.
  • Negative pregnancy test for females. who have reached menarche.
  • 87. All females of childbearing potential and sexually active males must agree to use an FDA approved method of birth control for up to 24 months after BMT or for as long as they are taking any medication that may harm a pregnancy, an unborn child or may cause a birth defect.
  • Individuals must meet all the following criteria to be eligible for this study.
  • Patient, parent, or legal guardian must have given written informed consent. For patients ≥ 16 years of age who are developmentally able, assent or affirmation will be obtained.
  • Age 1618-705560, inclusive, at time of consent. Patients up to age 24, diagnosed with SSc at age ≤ 19, will be included in Cohort 1 and evaluated according to the Pediatric and Young Adult criteria listed in sections 3.1.1 and 3.1.2.
  • Diagnosed with Systemic Sclerosis (SSc), according to the 2013 ACR/EULAR criteria (van den Hoogen et al., 2013).
  • All patients must meet either the following skin or ILD criteria. Disease duration is defined as time from first non-Raynaud symptom.
  • Skin Criteria: Diffuse SSc, defined by presence of proximal skin thickening and:
  • If disease duration is of <2 years, patients must have a calculated mortality risk prediction score which places them in the intermediate or high- risk category (Domsic et al., 2016). Refer to Appendix 5 for calculation criteria.
  • If disease duration is of >2 years, patients must have evidence of active cutaneous disease based upon 1) a worsening Modified Rodnan Skin Score (MRSS) in the preceding three months or 2) the presence of palpable tendon friction rubs.
  • ILD Criteria:
  • The presence of recognized fibrosis on imaging of <2 years AND either > 10% of lung involvement by CT scan or FVC% pred <80% or B. Fibrosis on imaging of any duration with a decline in FVC% pred of ≥10% over the preceding 12-18 months.
  • Negative for human immunodeficiency virus (HIV), hepatitis B virus and hepatitis C virus, all confirmed by PCR testing.
  • Negative pregnancy test for females.
  • All females of childbearing potential and sexually active males must agree to use an FDA approved method of birth control for up to 24 months after BMT or for as long as they are taking any medication that may harm a pregnancy, an unborn child or may cause a birth defect.
  • Exclusion Criteria Individuals who meet any of these criteria are not eligible for this study.
  • Moderate to severe cardiac involvement defined by any of the following:
  • New York Heart Association classification of heart failure ≥3.
  • Left ventricular ejection fraction (LVEF) <50% as determined by cardiac MRI.
  • Significant pulmonary hypertension, for subjects ≥ 18 years of age, defined as mean PASP ≥30 mmHg determined by right heart catheterization, or for subjects ≤ 17 years of age, defined as mean PASP >45 mmHg, determined by echocardiogram.
  • Atrial tachycardia, atrial fibrillation or atrial flutter of ≥1-minute duration, determined by electrocardiogram (EKG) or, cardiac event monitor and/or implanted loop recorder (if applicable), or on anti-arrhythmic therapy for the arrhythmias listed above.
  • Ventricular tachycardia of ≥6 beats at rate of ≥100 beats per minute, determined by EKG or, cardiac event monitor and/or implanted loop recorder (if applicable), or on an anti-arrhythmic therapy for any ventricular arrhythmia.
  • Left bundle branch block, bifascicular heart block, Mobitz 2 heart block, complete heart block or infarction pattern as determined by EKG or, cardiac event monitor and/or implanted loop recorder
  • Presence of pacemaker or implantable cardioverter defibrillator.
  • Moderate to severe pulmonary involvement defined by any of the following:
  • Hemoglobin-corrected DLCO <45%, determined by pulmonary function tests.
  • FVC <45%, determined by pulmonary function tests.
  • pO2 <70 mmHg, determined by an arterial blood gas (not applicable for subjects ≤17 years of age).
  • pCO2 ≥45 without supplemental O2 determined by an arterial blood gas (not applicable for subjects ≤17 years of age).
  • O2 sat <92% at rest without supplemental O2, determined by an arterial blood gas (not applicable for subjects ≤17 years of age).
  • Six-minute walk (6MW) results <400 feet.
  • Steroid therapy defined by either of the following:
  • Subjects who received > 10 mg/day prednisone or equivalent within 30 days prior to start of conditioning regimen on Day -21.
  • Subjects who have been treated for concurrent illnesses (eg, asthma) with the equivalent of prednisone 1 mg/kg/day or its equivalent for > 5 days on > 2 occasions during the previous 12 months (prior to conditioning) or > 1 occasion in the prior 6 months (prior to conditioning).
  • Estimated CrCl <40 mL/min,using Cockcroft-Gault formula based on actual body weight.
  • Serum creatinine >2.0 mg/dL.
  • Active, untreated SSc renal crisis at the time of consent.
  • Dependence on nutritional supplementation/hyperalimentation.
  • Active gastric antral vascular ectasia (GAVE), defined by a decrease in hemoglobin greater than 1 g/dL in the preceding 60 days, attributed to GAVE.
  • Active hepatitis defined by any of the following:
  • AST > 2x upper limit of normal.
  • ALT > 2x upper limit of normal.
  • Bilirubin >2x upper limit of normal.
  • Evidence of moderate to severe periportal fibrosis, determined by liver biopsy, if applicable.
  • Active, uncontrolled infection that would be a contraindication to safe use of high-dose immunosuppressive therapy or cyclophosphamide.
  • Hematologic abnormalities as defined by any of the following peripheral blood counts:
  • ANC < 1500 cell/µL.
  • Platelets < 100,000 cells/ µL.
  • Hemoglobin < 9.0 g/dL.
  • Evidence of myelodysplasia (MDS), confirmed by bone marrow aspirate, if applicable.
  • Malignancy within 2 years prior to enrollment, excluding adequately treated squamous cell cancer, basal cell carcinoma or carcinoma in situ. Treatment should have been completed with cure/remission status documented for at least 2 years, with the exception of hormonal therapy for breast cancer.
  • Females who are pregnant or who are lactating.
  • Tobacco use, by subject admission, within previous 4 weeks of time of consent.
  • History of sensitivity to murine proteins or E. coli proteins.
  • Known history of substance abuse, determined by medical record or subject admission, within 6 months of time of consent.
  • Patient with systemic reaction to anti-thymocyte globulin or any other equine gamma globulin preparation
  • Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.

Who cannot join

  • Individuals who meet any of these criteria are not eligible for this study.
  • FVC <35%, determined by pulmonary function tests for those able to complete spirometry adequately (per investigator's determination)
  • O2 sat <92% at rest in room air
  • Estimated CrCl <40 mL/min,using Cockcroft-Gault formula based on actual body weight.
  • Active, untreated SSc renal crisis at the time of consent.
  • ALT > 4x upper limit of normal.
Show all 14Show fewer
  • Active, uncontrolled infection that would be a contraindication to safe use of high-dose immunosuppressive therapy or cyclophosphamide.
  • Hematologic abnormalities as defined by any of the following peripheral blood counts:
  • ANC < 1500 cell/µL.
  • Platelets < 100,000 cells/ µL.
  • Hemoglobin < 9.0 g/dL.
  • Malignancy within 2 years prior to enrollment, excluding adequately treated squamous cell cancer, basal cell carcinoma or carcinoma in situ. Treatment should have been completed with cure/remission status documented for at least 2 years.
  • Past or current medical problems or findings from medical history, physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.
  • Cohort 2 for Adults

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Paul Szabolcs, MD contact

412-692-6225

paul.szabolcs@chp.edu

Shawna McIntyre, RN contact

412-692-5552

mcintyresm@upmc.edu

United States3 sites, 3 recruiting

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15213

    Shawna McIntyre, RN, 412-692-5552, mcintyresm@upmc.edu

    Paul Szabolcs, MD

    Recruiting

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15261

    Robyn Domsic, MD, MPH, 412-383-8000, domsicrt@upmc.edu

    Recruiting

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15261

    Robert Lafyatis, MD, 412-647-6700, lafyatisra@upmc.edu

    Recruiting

Other trials in United States

About this study

Official title: Autologous Stem Cell Transplantation With CD34-Selected Peripheral Blood Stem Cells (PBSC) in Patients With Treatment Resistant Systemic Sclerosis (SSc)

The purpose of this study is to determine whether a regimen of high-dose immunoablative therapy will demonstrate safety that is consistent or improved with other published regimens in SSc patients, while maintaining a treatment effect.

Read the detailed description

This is a single center, phase II trial where after a process of stem cell mobilization and conditioning, subjects receive a CD34-selected autologous peripheral blood stem cell rescue. By virtue of positive selection for the stem/progenitor cell marker of CD34, the graft will be depleted for T, B and NK lymphocytes and other immune cells such as monocytes that may be pathogenic. This is an open label study and there will be no randomization or blinding as a part of this study.

The proposed regimen of high-dose immunoablative therapy will demonstrate safety that is consistent or improved with other published regimens in SSc patients, while maintaining a treatment effect.

The primary objectives of this study are to determine the safety and treatment effect of high-dose immunoablative therapy followed by transplantation of CD34+ positively selected peripheral blood stem cells (PBSC) for systemic scleroderma (SSc) patients using a regimen designed to maximize patient safety while also aiming to eradicate autoreactive clones responsible for the disease. Safety will be determined by monitoring for death of any cause, and severe or life-threatening infections. Treatment effect will be determined by assessing event-free survival in comparison to a SSc observational cohort control group treated with standard of care medication (mycophenolate mofetil) at 12 and 36 months post hematopoietic stem cell transplant (HSCT). Enrolled subjects will be followed for survival, secondary malignancies, and SSC activity at least yearly up to 36 months post-HSCT.

The secondary objectives of this study are to:

  • To assess cutaneous disease response to high dose immunosuppressive therapy (HDIT) by comparing pre- and post-transplant measurements of the modified Rodnan skin score (mRSS).
  • To assess pulmonary disease response by longitudinally tracking FVC (pulmonary function test) and DLCO (diffusing capacity of the lung for carbon monoxide) yearly up to 36 months post-HSCT.
  • To evaluate the treatment effect on disease activity/progression, as indicated by severity measures of cardiac, pulmonary, musculoskeletal, gastrointestinal, vascular and renal organ involvement, and need for concomitant disease-modifying antirheumatic drugs (DMARD) use.
  • To evaluate quality of life by comparing pre- and post-transplant quality of life measurements. These measurements will include the Scleroderma Health Assessment Questionnaire (SHAQ), the Medical Outcomes Study Questionnaire Short Form 36 Health Survey (SF-36) and the Scleroderma Skin Patient Reported Outcome (SSPRO) pre- and post-mobilization.
Being tested
Cyclophosphamide, Mesna, Rituximab, Alemtuzumab, Thiotepa
Keywords
Stem Cell Transplantation, Systemic Sclerosis, Scleroderma, Interstitial Lung Disease, ILD (Interstitial Lung Disease), Pulmonary Hypertension, BMT ( bone marrow transplantation), Autologous
Medical subject headings
Scleroderma, Systemic, Scleroderma, Diffuse, Lung Diseases, Interstitial, Hypertension, Pulmonary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Stem Cell Mobilization

  • MesnaDrug

    Stem Cell Mobilization

  • RituximabDrug

    Also called Rituxan

    Transplantation Conditioning

  • AlemtuzumabDrug

    Also called Campath-1H

    Transplantation Conditioning

  • ThiotepaDrug

    Transplantation Conditioning

  • GM-CSFDrug

    Also called Neupogen, Filgrastim

    Transplantation Conditioning

  • Intravenous immunoglobulinDrug

    Transplantation Conditioning

  • Total Body IrradiationRadiation

    Transplantation Conditioning

  • Anti Thymocyte GlobulinDrug

    Also called Thymoglobulin

    Transplantation Conditioning

Study groups in NCT03630211
Study groupRoleWhat they receive
Autologous Stem Cell TransplantationExperimentalCD34-selected autologous stem cell being performed on CliniMACS depletion device. Conditioning regimen will not start sooner than 3 weeks, and ideally no more than 90 days, after cyclophosphamide dose in the mobilization regimen.
Receives: Drug: Cyclophosphamide; Drug: Mesna; Drug: Rituximab; Drug: Alemtuzumab; Drug: Thiotepa; Drug: GM-CSF; Drug: Intravenous immunoglobulin; Radiation: Total Body Irradiation; Drug: Anti Thymocyte Globulin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. High Dose Immunoablative therapy-Safety

    Safety will be determined by monitoring for death of any cause, regimen-related toxicities, and severe or life-threatening infections.

    Measured: Up to 36 months post HSCT

  2. Death

    How many, if any, patients die

    Measured: Post Transplant through study completion, an average of 36 months

  3. Respiratory Failure

    defined by one of the following 3 criteria without explanation for causation other than disease progression: 1. decline in DLCO of ≥30% or FVC≥20% as measured by actual difference in percent predicted units; 2. Resting arterial p02 < 60 mmHg or pCO2 > 50 mmHg supplemental oxygen;3. Resting pulse oximetry of 88% or lower measured by forehead probe.

    Measured: Post Transplant through study completion, an average of 36 months

  4. Renal Failure

    Defined by chronic dialysis for >6 months or renal transplantation

    Measured: Post Transplant through study completion, an average of 36 months

  5. The occurrence of cardiomyopathy

    confirmed by clinical congestive heart failure (New York Heart Association) or LVEF (left ventricular ejection fraction) <30% on echocardiogram

    Measured: Post Transplant through study completion, an average of 36 months

  6. Treatment-related mortality (TRM)

    defined as death occurring at any time after stem cell mobilization and definitely or probably resulting from treatment given in the study. TRM will be determined yearly with a focus on the first 2 years.

    Measured: Mobilization through study completion, an average of 36 months

  7. High Dose Immunoablative therapy-Treatment Effect

    Treatment effect will be determined by assessing event-free survival in comparison to a SSc observational cohort control group treated with standard of care medication (mycophenolate mofetil) at 12 and 36 months post hematopoietic stem cell transplant (HSCT).

    Measured: up to 36 months post HSCT (hematopoietic stem cell transplantation)

Secondary outcomes (6)

  1. An increase of mRSS (modified Rodnan skin score ) by ≥5 points for skin score

    To assess cutaneous response the modified Rodnan skin score (mRSS) will be used.

    Measured: Disease response will be defined as subject improvement. This will be assessed for both skin and interstitial lung disease at 12 and 24 months post-HSCT.

  2. Increase by ≥25% if the baseline mRSS > 20.

    To assess cutaneous response the modified Rodnan skin score (mRSS) will be used.

    Measured: Disease response will be defined as subject improvement. This will be assessed for both skin and interstitial lung disease at 12 and 24 months post-HSCT.

  3. Worsening of > 10% of FVC (pulmonary function testing)

    to evaluate interstitial lung disease an increase of ≥15% in DLCO or ≥10% of FVC (actual change in % predicted units from baseline) sustained for ≥3 months on 2 determinations.

    Measured: 1 year post transplant through study completion, an average of 36 months

  4. Decrease in DLCO sustained for 3 months or longer on pulmonary function tests (PFT)

    to evaluate interstitial lung disease an increase of ≥15% in DLCO or ≥10% of FVC (actual change in % predicted units from baseline) sustained for ≥3 months on 2 determinations.

    Measured: 1 year post transplant through study completion, an average of 36 months

  5. Worsening of cardiac involvement

    With use of Imaging, EKG, Echocardiogram, Cardiac MRI, right heart cauterization, implanted loop recorder and 2 week cardiac event monitor. Defined as new or worsening arrhythmias that require medical treatment of 3 months or longer, or require ablative therapy, pacemaker or defibrillator insertion or defined as a decline in ejection fraction of ≥10 EF units, determined by echocardiogram.

    Measured: Post Transplant through study completion, an average of 36 months

  6. Development of scleroderma renal crisis (hypertensive or non-hypertensive)

    Hypertensive renal crisis can be defined as a rise in SBP ≥ 30 points or DBP ≥ 20 points from baseline and one of the following: 1) Increase in baseline serum creatinine of ≥ 50%, 2) thrombocytopenia < 100,000 plts/mm3 or 3. hemolysis by blood smear or increased reticulocyte count.

    Measured: Post Transplant through study completion, an average of 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Aug 2018
  2. Study start31 Jul 2018
  3. Primary completion1 Aug 2028 (estimated)
  4. Study completion1 Aug 2028 (estimated)

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
8 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03630211
Sponsor's protocol ID
STUDY19050297
Acronym
SSc
Status last verified
Aug 2026
First submitted
7 Aug 2018
Last updated
14 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Torok KS, Horvei P, Li J, Rosser F, Alexander JL, Rose-Felker K, Sood V, Olson A, Hogue N, Vandergrift V, Stanczak H, Miglioretti M, Farver L, Koster W, Mcguire D, Havrilla H, McIntyre S, Domsic RT, Lafyatis RA, Szabolcs P. Autologous stem cell transplantation (ASCT) for Refractory juvenile-onset systemic sclerosis (JSSc). Ann Rheum Dis. 2026 Jun 17:S0003-4967(26)00299-2. doi: 10.1016/j.ard.2026.05.022. Online ahead of print.

    PubMed 42309868

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cyclophosphamide, Mesna and Rituximab in people with Systemic Sclerosis and Diffuse Sclerosis Systemic, run by Paul Szabolcs at 3 sites 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 72 inclusion and 14 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: looking for participants now, as of the sponsor's last update on 14 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Paul Szabolcs, MD (412-692-6225, paul.szabolcs@chp.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

High Dose Immunoablative therapy-Safety (time frame: Up to 36 months post HSCT). The study lists 7 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 NCT03630211, which also lists 1 linked publication.

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 14 Aug 2026.

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