A subset of autoimmune diseases (ADs) in children and young adults are life-threatening and unresponsive to conventional treatments. In these patients, the delivery of high dose immunosuppressive therapy followed by autologous stem cell transplant (ASCT) offers a treatment strategy capable of purging the pathogenic, autoreactive immune system and an opportunity for "immune reset." This strategy has been used in adults across a myriad of indications with evidence for efficacy. This study proposes a pilot study to evaluate this therapeutic strategy in children and young adults with systemic sclerosis (SSc) and systemic lupus erythematosis (SLE), two potentially life threatening autoimmune diseases that may response to this therapeutic approach.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
The purpose of this study is to determine the safety and feasibility of CD3/CD19 depleted autologous stem cell transplant for the treatment of life threatening autoimmune disease. We will perform CD3/CD19 depletion using the CliniMACs device as a means of purging autoreactive T and B cells from the transfused autologous stem cell product, while retaining some immune function, namely natural killer cells and monocytes in the product.
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
RECRUITINGTwo-year progression free survival
Survival without evidence of relapse or disease progression
Time frame: 2 years
Disease-specific response/progression endpoints: SSc cohort
o Pulmonary function: Change in forced vital capacity (FVC), total lung capacity (TLC) or diffusing capacity of the lung for carbon monoxide (DLCO) \> 10%
Time frame: 24 months following transplant
Disease-specific response/progression endpoints: SSc cohort
o Skin condition: An improvement is indicated by a decrease on modified Rodan Skin Score (mRSS) of \> 5 points
Time frame: 24 months following transplant
Disease-specific response/progression endpoints: Systemic Lupus Erythematosus (SLE) cohort
o Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) \< 4
Time frame: 24 months following transplant
Disease-specific response/progression endpoints: Systemic Lupus Erythematosus (SLE) cohort
o Complete remission off therapy (BILAG D/E only or SLEDAI=0 and no SLE treatment except hydroxychloroquine)
Time frame: 24 months following transplant
Disease-specific response/progression endpoints: Systemic Lupus Erythematosus (SLE) cohort
o Serologic response: presence of positive ANA, anti-dsDNA and anticardiolpin antibody titers
Time frame: 24 months following transplant
Disease-specific response/progression endpoints: Systemic Lupus Erythematosus (SLE) cohort
o Serologic response: abnormal complement C3 and C4 levels
Time frame: 24 months following transplant
Overall survival (OS)
Overall survival will be considered as time from transplant to death from any cause
Time frame: 2 and 5 years following transplant
Event free survival (EFS)
Events include death, and significant persistent organ damage o An event based on organ dysfunction must be documented on at least two occasions, at least three months apart and include: respiratory failure (resting O2 saturation \< 88%), renal failure (chronic dialysis) and cardiomyopathy (clinical congestive heart failure New York Class III or IV, left ventricular ejection fraction (LVEF) \< 30% by echocardiogram despite therapy)
Time frame: 2 and 5 years following transplant
100 day treatment-related mortality
Defined as death from non-disease related causes in the 100 days from stem cell infusion
Time frame: 100 days from stem cell infusion
Time to engraftment
• Achieving an absolute neutrophil count (ANC) \> 500 cells/uL and an unsupported platelet count of \> 20,000 cells/uL for three consecutive days
Time frame: 3 days
Change in quality of life
* Quality of life will be measured based on the Patient-Reported Outcomes measurement Information System (PROMIS) that evaluates physical, mental and social health in adults and children. * patient reported outcome measurement information system (PROMIS) will be administered to each patient (or proxy) prior to autologous stem cell transplant (ASCT) and three times/year for the first two years post-transplant and then annually until five years post-transplant.
Time frame: prior to autologous stem cell transplant (ASCT) until 5 years post-transplant
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