Autologous Stem Cell Transplant (ASCT) for Autoimmune Diseases

Systemic Lupus Erythematosus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05029336
• Other study ID #: 19-016604
• Status: Recruiting
• Phase: Phase 2
• Start date: May 2024
• Est. completion date: May 2031

Study information

• Verified date: November 2023
• Source: Children's Hospital of Philadelphia
• Contact: Jessica H Lee, BS
• Phone: 267-425-1935
• Email: leej11[@]chop.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: May 2031
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years to 25 Years

Eligibility

Inclusion Criteria:

1. Age 8 = 25 years at time of enrollment.

2. Severe systemic sclerosis or systemic lupus erythematosus based on specific criteria

3. Adequate organ function status

4. No active, untreated infections.

Exclusion Criteria:

1. Previous hematopoietic stem cell transplant (HSCT) or solid organ transplant

2. Pregnancy

3. Ongoing participation in a clinical trial testing an investigational drug or ongoing receipt of disallowed disease modifying anti-rheumatic drugs (DMARD)

4. Severe comorbidity that jeopardizes the ability of the subject to tolerate therapy

Related Conditions & MeSH terms

• Autoimmune Diseases
• Lupus Erythematosus, Systemic
• Scleroderma, Diffuse
• Scleroderma, Systemic
• Systemic Lupus Erythematosus
• Systemic Sclerosis

Intervention

Biological:
• Depletion of CD3/CD19 in an autologous stem cell transplant
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.

Locations

Country	Name	City	State
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Stephan Grupp MD PhD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Two-year progression free survival	Survival without evidence of relapse or disease progression	2 years
Secondary	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
Secondary	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
Secondary	Disease-specific response/progression endpoints: Systemic Lupus Erythematosus (SLE) cohort	o Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) < 4	24 months following transplant
Secondary	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
Secondary	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
Secondary	Disease-specific response/progression endpoints: Systemic Lupus Erythematosus (SLE) cohort	o Serologic response: abnormal complement C3 and C4 levels	24 months following transplant
Secondary	Overall survival (OS)	Overall survival will be considered as time from transplant to death from any cause	2 and 5 years following transplant
Secondary	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
Secondary	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
Secondary	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
Secondary	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