Autologous Stem Cell Transplant (ASCT) for Autoimmune Diseases

Study Overview
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Brief Summary
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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.

Official Title
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Autologous Hematopoietic Stem Cell Transplant for Children and Young Adults With Life Threatening Autoimmune Diseases

Conditions
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Systemic Lupus Erythematosus, Systemic Sclerosis

Intervention / Treatment
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* Biological: Depletion of CD3/CD19 in an autologous stem cell transplant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 8 ≤ 25 years at time of enrollment. Severe systemic sclerosis or systemic lupus erythematosus based on specific criteria Adequate organ function status No active, untreated infections. Exclusion Criteria: Previous hematopoietic stem cell transplant (HSCT) or solid organ transplant Pregnancy Ongoing participation in a clinical trial testing an investigational drug or ongoing receipt of disallowed disease modifying anti-rheumatic drugs (DMARD) Severe comorbidity that jeopardizes the ability of the subject to tolerate therapy

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: open label single arm pilot study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CD3/CD19 depleted ASCT<br>The test article is autologous stem cell transplant with a CD3/CD19-depleted stem cell product. | Biological: Depletion of CD3/CD19 in an autologous stem cell transplant<br>* 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.<br>* Other names: CD3/CD19 depletion using cliniMACs device;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Two-year progression free survival | Survival without evidence of relapse or disease progression | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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% | 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 | 24 months following transplant | 
| Disease-specific response/progression endpoints: Systemic Lupus Erythematosus (SLE) cohort | o Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) < 4 | 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) | 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 | 24 months following transplant | 
| Disease-specific response/progression endpoints: Systemic Lupus Erythematosus (SLE) cohort | o Serologic response: abnormal complement C3 and C4 levels | 24 months following transplant | 
| Overall survival (OS) | Overall survival will be considered as time from transplant to death from any cause | 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) | 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 | 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 | 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. | prior to autologous stem cell transplant (ASCT) until 5 years post-transplant |