Stem Cell Transplant for Autoimmune Diseases

Overseen By Jessica H Lee, BS

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Stephan Grupp

Must not be taking: DMARDs

Disqualifiers: Pregnancy, Previous transplant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications, but you cannot be on disallowed disease modifying anti-rheumatic drugs (DMARDs) or participate in another clinical trial with investigational drugs.

What data supports the idea that Stem Cell Transplant for Autoimmune Diseases is an effective treatment?

The available research shows that Stem Cell Transplant for Autoimmune Diseases, specifically Autologous Hematopoietic Stem Cell Transplantation (AHSCT), can lead to significant improvements. It has been noted to improve quality of life and induce remission for several years in some cases. Unlike other treatments that require ongoing medication and can have side effects, AHSCT can lead to long-lasting remission without the need for continuous therapy. This suggests that AHSCT might be more effective in providing a durable solution compared to conventional treatments, which are rarely curative. ^{1 2 3 4 5}

What safety data is available for stem cell transplants in autoimmune diseases?

Safety data for autologous hematopoietic stem cell transplantation (AHSCT) in autoimmune diseases indicates that while it is a feasible treatment option, it can be associated with significant risks. Studies have shown that AHSCT can lead to infectious complications, particularly in patients with low B cell counts, and may require ongoing immunosuppressive therapy. Phase I trials have demonstrated its feasibility, and long-term follow-up in multiple sclerosis patients shows varied clinical outcomes. Overall, AHSCT is effective but carries potential morbidity and mortality risks. ^{1 6 7 8 9}

Is the treatment Autologous Stem Cell Transplant (ASCT) promising for autoimmune diseases?

Yes, Autologous Stem Cell Transplant (ASCT) is considered a promising treatment for severe autoimmune diseases. It has shown potential in helping patients achieve remission, especially in conditions like multiple sclerosis and systemic sclerosis. The treatment aims to reset the immune system, which can lead to prolonged periods without disease symptoms. ^{10 11 12 13 14}

Research Team

Caitlin Elgarten, MD

Principal Investigator

Children's Hospital of Philadelphia

Eligibility Criteria

This trial is for young individuals aged 8-25 with severe systemic sclerosis (SSc) or systemic lupus erythematosus (SLE). They must have specific disease characteristics, good organ function, and no current untreated infections. It's not open to those who've had previous transplants, are pregnant, in other drug trials, or have severe health issues affecting therapy tolerance.

Inclusion Criteria

I am between 8 and 25 years old.

I do not have any untreated infections.

I have been diagnosed with severe systemic sclerosis or lupus.

Exclusion Criteria

I have a serious health condition that may affect my ability to handle treatment.

I am not currently in a trial for a new drug or taking certain arthritis medications.

Pregnancy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

High Dose Immunosuppressive Therapy

Participants receive high dose immunosuppressive therapy to purge the pathogenic, autoreactive immune system

2-4 weeks

Autologous Stem Cell Transplant (ASCT)

Participants undergo autologous stem cell transplant with a CD3/CD19-depleted stem cell product

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, including quality of life assessments and survival outcomes

5 years

Treatment Details

Interventions

• Autologous Stem Cell Transplant (ASCT)

Trial Overview The study tests a treatment where patients' own stem cells are modified by removing certain immune cells (CD3/CD19) and then returned to the body. This aims to reset their immune system and improve life-threatening autoimmune diseases like SSc and SLE in children and young adults.

Participant Groups

Group I: CD3/CD19 depleted ASCT Experimental Treatment 1 Intervention

The test article is autologous stem cell transplant with a CD3/CD19-depleted stem cell product.

Autologous Stem Cell Transplant (ASCT) is already approved in European Union, United States for the following indications:

Approved in European Union as Autologous Hematopoietic Stem Cell Transplantation (AHSCT) for:

• Systemic sclerosis (SSc)
• Multiple sclerosis (MS)
• Crohn’s disease
• Juvenile idiopathic arthritis (JIA)

Approved in United States as Autologous Hematopoietic Stem Cell Transplantation (AHSCT) for:

• Severe systemic sclerosis (SSc)
• Rapidly progressive scleroderma

Who Is Running the Clinical Trial?

Stephan Grupp

Lead Sponsor

Trials

1

Recruited

20+

Stephan Grupp MD PhD

Lead Sponsor

Trials

5

Recruited

370+

Findings from Research

In a study of 22 patients with systemic sclerosis (SSc) undergoing autologous haematopoietic stem cell transplantation (AHSCT), there was a significant increase in naïve B cell frequencies over the year following treatment, indicating a reconstitution of a healthier immune system.

The study also found that regulatory B cells (Bregs) improved their ability to suppress harmful T cell activity by 360 days post-AHSCT, suggesting that AHSCT may enhance immunoregulatory functions and contribute to clinical remission in SSc patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous haematopoietic stem cell transplantation restores the suppressive capacity of regulatory B cells in systemic sclerosis patients. Lima-Júnior, JR., Arruda, LCM., Gonçalves, MS., et al.[2022]

Autologous hematopoietic stem cell transplantation (HSCT) has shown promising results in treating autoimmune diseases, leading to improved quality of life and remission lasting several years, suggesting further research is needed, particularly in phase III trials.

Allogeneic HSCT is being explored for high-risk autoimmune patients at Northwestern University, focusing on strategies to reduce toxicity and graft-versus-host disease (GVHD), aiming for a potential cure for these challenging conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic stem cell transplantation for autoimmune diseases: nonmyeloablative conditioning regimens. Oyama, Y., Traynor, AE., Barr, W., et al.[2007]

Stem cell transplantation (SCT) has gained attention as a potential treatment for severe autoimmune diseases, showing some promise based on early experiences and animal studies.

However, randomized studies are needed to truly assess the effectiveness of autologous SCT, and future research should also explore allogeneic SCT as a possible alternative since autologous SCT may not provide a cure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stem cell transplantation in autoimmune diseases: an update. Jantunen, E., Luosujärvi, R.[2005]

High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (AHSCT) can be an effective salvage therapy for patients with severe, refractory autoimmune diseases, with a 16.7% transplantation-related mortality rate observed in a study of 12 patients over 24 months.

Immune reconstitution after AHSCT occurs in phases, with natural killer (NK) cells and CD8+ T cells appearing first, while B cells and CD4+ T cells normalize within 150 days, indicating a gradual rebuilding of the immune system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunological reconstitution after autologous stem cell transplantation in patients with refractory systemic autoimmune diseases. Szodoray, P., Varoczy, L., Papp, G., et al.[2012]

Autologous hematopoietic stem cell transplantation (AHSCT) can induce long-lasting clinical remission in autoimmune diseases without the need for ongoing maintenance therapy, unlike traditional biologic and targeted synthetic drugs that require continuous administration.

AHSCT works by eliminating autoreactive immune memory and regenerating the immune system, leading to fundamental changes in the immune repertoire and promoting tolerance to self-antigens, as supported by registry data from the European Society of Blood and Marrow Transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Autologous hematopoietic stem cell transplantation for autoimmune diseases : Current indications and mode of action, a review on behalf of the EBMT Autoimmune Diseases Working Party (ADWP)]. Alexander, T., Badoglio, M., Henes, J., et al.[2020]

In a study of 17 systemic sclerosis patients undergoing autologous hematopoietic stem cell transplantation (aHSCT), 50% of CMV-IgG-positive patients experienced reactivations of cytomegalovirus, highlighting the need for careful monitoring and treatment of infections post-transplant.

Patients who developed infections after aHSCT had significantly lower levels of B cells before the procedure, suggesting that low peripheral B cell counts may be a risk factor for increased infection rates during the prolonged immune reconstitution period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low B cell counts as risk factor for infectious complications in systemic sclerosis after autologous hematopoietic stem cell transplantation. Gernert, M., Tony, HP., Schwaneck, EC., et al.[2021]

Phase I trials have shown that autologous hematopoietic stem cell transplantation (HSCT) is feasible and safe for patients with autoimmune diseases.

The ongoing phase II trials are focusing on the efficacy of using gene-marked autologous stem cells, building on the safety results from the earlier phase I trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene-marked autologous hematopoietic stem cell transplantation of autoimmune disease. Burt, RK., Brenner, M., Burns, W., et al.[2019]

In a study of 14 patients with severe multiple sclerosis, autologous hematopoietic stem cell transplantation (AHSCT) showed a 62.5% probability of progression-free survival after 6 years, indicating its potential to stabilize the disease.

The procedure was associated with no long-term complications, suggesting it is a relatively safe option for patients, although it is not considered a curative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical outcome 6 years after autologous hematopoietic stem cell transplantation in multiple sclerosis]. Saiz, A., Blanco, Y., Berenguer, J., et al.[2008]

In a study of 27 systemic sclerosis patients who underwent autologous hematopoietic stem cell transplantation (aHSCT), 59.3% required immunosuppressive medication (IS) post-transplant due to disease progression, indicating that some patients may still need additional treatment after aHSCT.

Rituximab was found to be effective in improving skin scores and stabilizing lung function in patients receiving IS after aHSCT, while the occurrence of severe adverse events was similar between those on IS and those not on it, suggesting that aHSCT has a reassuring safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunosuppressive Therapy After Autologous Hematopoietic Stem Cell Transplantation in Systemic Sclerosis Patients-High Efficacy of Rituximab. Gernert, M., Tony, HP., Fröhlich, M., et al.[2022]

Autologous hematopoietic stem cell transplantation (HSCT) has been successfully used to treat around 3000 patients with severe autoimmune diseases, showing significant long-term survival benefits, particularly in systemic sclerosis, despite some early transplant-related mortality.

The primary goal of HSCT is to 'reset' the immune system to a naïve state, which requires careful patient selection and collaboration among healthcare professionals to achieve the best outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of stem cell transplantation in autoimmune diseases. Ng, SA., Sullivan, KM.[2020]

In a study involving five patients with various autoimmune diseases, autologous stem cell transplantation (using either bone marrow or peripheral blood progenitor cells) did not lead to lasting improvements, as signs of autoimmune disease recurred or persisted after treatment.

These findings suggest that high-dose therapy followed by transplantation of unmanipulated autologous stem cells may not be an effective treatment for severe autoimmune diseases, highlighting the need for caution in considering this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early recurrence or persistence of autoimmune diseases after unmanipulated autologous stem cell transplantation. Euler, HH., Marmont, AM., Bacigalupo, A., et al.[2021]

Autologous hematopoietic stem cell transplantation (HCT) has shown significant efficacy in treating refractory multiple sclerosis (MS) and advanced systemic sclerosis (SSc) in recent phase trials, outperforming standard therapies like disease-modifying drugs and cyclophosphamide.

While evidence for HCT in MS and SSc is strong, further large-scale trials are needed for lupus, and ongoing research is focused on optimizing patient selection and treatment protocols to enhance safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stem Cell Therapy as a Treatment for Autoimmune Disease-Updates in Lupus, Scleroderma, and Multiple Sclerosis. Ramalingam, S., Shah, A.[2021]

In a study of 4 patients with autoimmune diseases (3 with psoriasis and 1 with rheumatoid arthritis) undergoing autologous bone marrow or stem cell transplantation (ABMT/ASCT) for hematologic malignancies, all patients experienced remission of their autoimmune conditions post-transplant.

However, the autoimmune diseases recurred within 8-24 months after transplantation, suggesting that while ABMT/ASCT can temporarily alleviate symptoms, it is unlikely to provide a permanent cure, indicating a need for further research into more effective treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of rheumatoid arthritis and psoriasis following autologous stem cell transplantation for hematologic malignancy. Cooley, HM., Snowden, JA., Grigg, AP., et al.[2022]

Hematopoietic stem cell transplantation (HSCT) is increasingly used to treat severe autoimmune diseases that do not respond to standard therapies, with autologous HSCT preferred due to its lower toxicity.

The success of HSCT in achieving long-term remission may depend on effectively eliminating autoreactive immune cells and allowing for the regeneration of a new immune system, tailored to the specific autoimmune disease being treated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The promise of hematopoietic stem cell transplantation for autoimmune diseases. Burt, RK., Traynor, AE., Craig, R., et al.[2004]

References

1. England pubmed.ncbi.nlm.nih.gov

Autologous haematopoietic stem cell transplantation restores the suppressive capacity of regulatory B cells in systemic sclerosis patients. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Allogeneic stem cell transplantation for autoimmune diseases: nonmyeloablative conditioning regimens. [2007]

3. England pubmed.ncbi.nlm.nih.gov

Stem cell transplantation in autoimmune diseases: an update. [2005]

4. England pubmed.ncbi.nlm.nih.gov

Immunological reconstitution after autologous stem cell transplantation in patients with refractory systemic autoimmune diseases. [2012]

5. Germany pubmed.ncbi.nlm.nih.gov

[Autologous hematopoietic stem cell transplantation for autoimmune diseases : Current indications and mode of action, a review on behalf of the EBMT Autoimmune Diseases Working Party (ADWP)]. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Low B cell counts as risk factor for infectious complications in systemic sclerosis after autologous hematopoietic stem cell transplantation. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Gene-marked autologous hematopoietic stem cell transplantation of autoimmune disease. [2019]

8. Spain pubmed.ncbi.nlm.nih.gov

[Clinical outcome 6 years after autologous hematopoietic stem cell transplantation in multiple sclerosis]. [2008]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Immunosuppressive Therapy After Autologous Hematopoietic Stem Cell Transplantation in Systemic Sclerosis Patients-High Efficacy of Rituximab. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Application of stem cell transplantation in autoimmune diseases. [2020]

11. United States pubmed.ncbi.nlm.nih.gov

Early recurrence or persistence of autoimmune diseases after unmanipulated autologous stem cell transplantation. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Stem Cell Therapy as a Treatment for Autoimmune Disease-Updates in Lupus, Scleroderma, and Multiple Sclerosis. [2021]

13. United States pubmed.ncbi.nlm.nih.gov

Outcome of rheumatoid arthritis and psoriasis following autologous stem cell transplantation for hematologic malignancy. [2022]

14. England pubmed.ncbi.nlm.nih.gov

The promise of hematopoietic stem cell transplantation for autoimmune diseases. [2004]