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.
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.
Progression of skin thickening over the past 6 months or Modified Rodnan skin score (mRSS) ≥ 20
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.
Single group
Cyclophosphamide
DrugStem Cell Mobilization
Mesna
DrugStem Cell Mobilization
Rituximab
DrugTransplantation Conditioning
Alemtuzumab
DrugTransplantation Conditioning
Thiotepa
DrugTransplantation Conditioning
GM-CSF
DrugTransplantation Conditioning
Intravenous immunoglobulin
DrugTransplantation Conditioning
Total Body Irradiation
RadiationTransplantation Conditioning
Anti Thymocyte Globulin
DrugTransplantation Conditioning
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.
Death
How many, if any, patients die
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.
Renal Failure
Defined by chronic dialysis for \>6 months or renal transplantation
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.
Increase by ≥25% if the baseline mRSS > 20.
To assess cutaneous response the modified Rodnan skin score (mRSS) will be used.
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.
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.
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Paul Szabolcs
Lead sponsor
University of Pittsburgh
Sponsor institution
