Last updated on April 2019

Autologous Stem Cell Transplantation in Patients With Systemic Sclerosis


Brief description of study

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. We also hypothesize that our mechanistic studies will yield biomarkers that may herald disease recurrence or progression following alterations in the recovery of immune cells in the skin and/or bronchial lavage or blood.

Detailed Study Description

This is a single center, phase II trial where after a process of stem cell mobilization and conditioning, adult 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 at least 3-log 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. We also hypothesize that our mechanistic studies will yield biomarkers that may herald disease recurrence or progression following alterations in the recovery of immune cells in the skin and/or bronchial lavage or blood.

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, regimen-related toxicities, 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 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.

The research (mechanistic) objectives are as follows:

  • Understand the effect of the combination of rituximab and alemtuzumab on lymphocyte subsets and myeloid cells in the skin of patients undergoing treatment.
  • Understand the effect of total body irradiation (TBI) and Thiotepa on subsets of lymphocytes and myeloid cells in the skin of patients undergoing treatment.
  • Understand the relationship between the response of patient skin disease to depletion and repopulation of skin leukocyte subpopulations and gene expression.
  • Characterize the evolution of humoral and cellular immune markers of autoreactivity in blood and BAL (bronchoalveolar lavage)when feasible

Clinical Study Identifier: NCT03630211

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Recruitment Status: Open


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