Autologous Stem Cell Transplantation in Patients With Systemic Sclerosis
- Conditions
- Interventions
- Registration Number
- NCT03630211
- Lead Sponsor
- Paul Szabolcs
- Brief 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.
- 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 th...
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 8
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Autologous Stem Cell Transplantation Total Body Irradiation CD34-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. Autologous Stem Cell Transplantation Anti Thymocyte Globulin CD34-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. Autologous Stem Cell Transplantation Intravenous immunoglobulin CD34-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. Autologous Stem Cell Transplantation Cyclophosphamide CD34-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. Autologous Stem Cell Transplantation Mesna CD34-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. Autologous Stem Cell Transplantation Rituximab CD34-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. Autologous Stem Cell Transplantation Alemtuzumab CD34-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. Autologous Stem Cell Transplantation GM-CSF CD34-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. Autologous Stem Cell Transplantation Thiotepa CD34-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.
- Primary Outcome Measures
Name Time Method Death Post Transplant through study completion, an average of 36 months How many, if any, patients die
Respiratory Failure Post Transplant through study completion, an average of 36 months 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.
High Dose Immunoablative therapy-Safety Up to 36 months post HSCT Safety will be determined by monitoring for death of any cause, regimen-related toxicities, and severe or life-threatening infections.
Renal Failure Post Transplant through study completion, an average of 36 months Defined by chronic dialysis for \>6 months or renal transplantation
Treatment-related mortality (TRM) Mobilization through study completion, an average of 36 months 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.
The occurrence of cardiomyopathy Post Transplant through study completion, an average of 36 months confirmed by clinical congestive heart failure (New York Heart Association) or LVEF (left ventricular ejection fraction) \<30% on echocardiogram
High Dose Immunoablative therapy-Treatment Effect up to 36 months post HSCT (hematopoietic stem cell transplantation) 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).
- Secondary Outcome Measures
Name Time Method An increase of mRSS (modified Rodnan skin score ) by ≥5 points for skin score 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. To assess cutaneous response the modified Rodnan skin score (mRSS) will be used.
Increase by ≥25% if the baseline mRSS > 20. 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. To assess cutaneous response the modified Rodnan skin score (mRSS) will be used.
Decrease in DLCO sustained for 3 months or longer on pulmonary function tests (PFT) 1 year post transplant through study completion, an average of 36 months 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.
Development of scleroderma renal crisis (hypertensive or non-hypertensive) Post Transplant through study completion, an average of 36 months 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.
Worsening of > 10% of FVC (pulmonary function testing) 1 year post transplant through study completion, an average of 36 months 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.
Worsening of cardiac involvement Post Transplant through study completion, an average of 36 months 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...
Trial Locations
- Locations (2)
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States