Stem Cell Transplant for Scleroderma

(STAT Trial)

No longer recruiting at 11 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Fred Hutchinson Cancer Research Center

Must be taking: MMF, Cyclophosphamide

Must not be taking: DMARDs

Disqualifiers: Pulmonary, Cardiac, Renal, Hepatic, 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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of treatments to evaluate their effectiveness in treating systemic scleroderma, a condition where the immune system attacks and hardens the body's tissues. The process involves collecting a patient's stem cells, administering high-dose chemotherapy and other medications to suppress the immune system, and then returning the stem cells to help rebuild healthy blood cells. After the transplant, patients take medication to prevent the scleroderma from worsening. This trial may suit individuals with systemic scleroderma and progressive symptoms, such as worsening lung or skin issues, who have not found success with treatments like cyclophosphamide or mycophenolate mofetil. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to benefit from a potentially effective new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that participants must be willing or able to discontinue certain disease-modifying antirheumatic drugs (DMARDs) before starting the treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that anti-thymocyte globulin and cyclophosphamide are both used to treat systemic scleroderma (SSc) and have been studied for their safety in people. Anti-thymocyte globulin lowers immune system activity but can lead to serious infections during treatment. In one study, a few patients experienced severe infections, but most did well, with some achieving good long-term results.

Cyclophosphamide is commonly used for SSc and has a well-known safety record. Studies have shown it can improve lung function and skin symptoms. However, it can cause significant side effects, such as infections and changes in blood cells. To manage these risks, the treatment is usually given for a limited time.

In summary, both treatments have been used before and have safety data, but they come with some risks. Patients in trials are closely monitored to manage any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike standard treatments for scleroderma, which often focus on managing symptoms with medications like methotrexate or mycophenolate mofetil, the treatment under study involves a stem cell transplant approach. This method is unique because it aims to reset the immune system by using high-dose immunosuppressive therapy followed by an autologous peripheral blood stem cell transplant (PBSCT). Researchers are excited about this treatment because it targets the disease at a fundamental level, potentially offering more lasting remission by rebuilding a healthier immune system. Additionally, the use of a patient's own stem cells reduces the risk of rejection and complications associated with donor transplants.

What evidence suggests that this treatment might be an effective treatment for scleroderma?

In this trial, participants will receive a combination of treatments, including cyclophosphamide and anti-thymocyte globulin, as part of the stem cell transplant process for scleroderma. Studies have shown that cyclophosphamide can help treat systemic sclerosis (SSc), particularly by improving lung issues related to scleroderma. Research indicates that patients with scleroderma who used cyclophosphamide experienced symptom improvement. Anti-thymocyte globulin has been linked to long-term remission in some patients with severe conditions. It calms the immune system, which can be overactive in scleroderma. Together, these treatments aim to reduce the disease's severity and improve patient outcomes. ^{1 2 3 6 7}

Who Is on the Research Team?

Leona Holmberg

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for patients with systemic scleroderma, specifically those who have had the disease for less than two years with severe skin involvement or lung problems, and those not responding to standard treatments. It's not open to individuals with a life expectancy under five years, prior stem cell transplants, uncontrolled infections, recent cancers (except certain skin cancers), GAVE ('watermelon stomach'), smokers in the last three months, pregnant women, or those unable to consent.

Inclusion Criteria

I have systemic sclerosis with skin involvement, not in Group 5, at risk of getting worse.

My condition did not improve after 4+ months on MMF/Myfortic or cyclophosphamide.

My gastrointestinal condition is getting worse.

Exclusion Criteria

I have lung, heart, liver, or kidney problems that could affect my treatment.

I cannot or will not stop taking certain medications for my scleroderma.

I have had a stem cell transplant using my own cells.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Stem Cell Mobilization and Preparation

Patients receive filgrastim and possibly cyclophosphamide or plerixafor to mobilize stem cells for collection

1-2 weeks

Multiple visits for apheresis

HDIT Conditioning

Patients receive high-dose cyclophosphamide and anti-thymocyte globulin to prepare for transplantation

1 week

Transplantation

Patients undergo autologous peripheral blood stem cell transplantation

1 day

Maintenance Therapy

Patients receive mycophenolate mofetil to prevent worsening or reactivation of systemic sclerosis

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Follow-up at 1 month, weeks 12 and 26, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Anti-Thymocyte Globulin
• Cyclophosphamide
• Filgrastim
• Mycophenolate Mofetil
• Plerixafor

Trial Overview The STAT study tests whether a combination of high-dose cyclophosphamide and anti-thymocyte globulin followed by autologous hematopoietic stem cell transplantation can treat systemic scleroderma. After transplanting the patient's own stored stem cells back into their body post-chemotherapy and immunosuppression therapy, maintenance therapy with mycophenolate mofetil is used to prevent worsening of SSc.

How Is the Trial Designed?

Group I: Treatment (HDIT autologous PBSCT) Experimental Treatment 10 Interventions

STEM CELL MOBILIZATION AND PREPARATION: Patients receive filgrastim SC on mobilization days 1-4 followed by apheresis until a target dose of CD34+ cells \>= 2.5 x 10\^6/kg are collected. Patients difficult to mobilize with filgrastim alone receive cyclophosphamide IV or \*plerixafor SC on mobilization days 1-2 and filgrastim SC on mobilization days 5-7. HDIT CONDITIONING: Patients receive high-dose cyclophosphamide IV over 1-2 hours on days -5 to -2 and anti-thymocyte globulin IV on days -5, -3, -1, 1, 3, and 5. TRANSPLANTATION: Patients undergo autologous PBSCT on day 0. MAINTENANCE THERAPY: Beginning 2-3 months after transplant, patients receive mycophenolate mofetil PO BID for 2 years.

Anti-Thymocyte Globulin is already approved in European Union, United States for the following indications:

Approved in European Union as Thymoglobulin for:

• Prevention and treatment of acute rejection following organ transplantation
• Severe aplastic anemia

Approved in United States as Thymoglobulin for:

• Prevention and treatment of acute rejection following kidney transplantation
• Severe aplastic anemia

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Research Center

Lead Sponsor

Trials

444

Recruited

148,000+

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

A study comparing four batches of antithymocyte globulins (ATGs) showed that both ATG-Fresenius and Thymoglobulin had consistent binding and functional properties when interacting with human leukocytes, suggesting similar clinical efficacy across different batches.

The research utilized flow cytometric assays to analyze the reactivity of ATGs with leukocytes, indicating that variations in batch preparation are unlikely to impact their effectiveness in preventing allograft rejection and graft versus host disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of batch to batch variation in polyclonal antithymocyte globulin preparations. Popow, I., Leitner, J., Majdic, O., et al.[2014]

In a study of six patients with steroid-resistant T-cell-mediated rejection after kidney transplantation, anti-thymocyte globulin (ATG) treatment led to a significant increase in T-cell repopulation from 24% to 75%, primarily driven by effector memory CD8+ T cells.

The administration of ATG also resulted in an increase in regulatory T cells, suggesting a potential mechanism for modulating immune responses, while other immune cell types like B cells and natural killer cells showed no significant changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Immune Cell Repopulation After Anti-thymocyte Globulin Administration for Steroid-Resistant T-cell-mediated Rejection. Sim, JH., Han, SS., Lee, DS., et al.[2020]

Haematopoietic stem cell transplant (HSCT) significantly alters the autoantibody repertoire in patients with systemic sclerosis, showing a more favorable outcome compared to cyclophosphamide (CTX) treatment, as evidenced by a study involving 45 participants from the SCOT trial.

Patients treated with HSCT exhibited significant changes in autoantibody levels against various antigens, suggesting that HSCT may stabilize the immune response, while CTX treatment did not show similar changes, indicating a potential mechanism for improved clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterising the autoantibody repertoire in systemic sclerosis following myeloablative haematopoietic stem cell transplantation. Ayoglu, B., Donato, M., Furst, DE., et al.[2023]

In a pilot study of 13 patients with recent-onset diffuse scleroderma, treatment with anti-thymocyte globulin (ATG) followed by mycophenolate mofetil (MMF) resulted in a significant decrease in skin score from 28 to 17 over 12 months, indicating improved skin condition.

While MMF was well tolerated, some patients experienced adverse effects, including serum sickness in five patients, which was manageable with corticosteroids, suggesting that while the treatment is generally safe, monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of anti-thymocyte globulin plus mycophenolate mofetil in recent-onset diffuse scleroderma. Stratton, RJ., Wilson, H., Black, CM.[2019]

A systematic review of 6 phase III randomized controlled trials found that rabbit antithymocyte globulin (ATG) formulations, particularly anti-T lymphocyte globulin (ATLG), are effective in preventing graft-versus-host disease (GVHD) after allogeneic stem cell transplantation, showing significantly better outcomes compared to standard treatments.

While both ATLG and Thymoglobulin (Thymo) had similar effects on transplantation-related mortality, Thymo showed a trend towards better overall survival, suggesting that Thymo may be a preferable option for improving long-term survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Different Rabbit Anti-Thymocyte Globulin Formulations in Allogeneic Stem Cell Transplantation: Systematic Literature Review and Network Meta-Analysis. Gagelmann, N., Ayuk, F., Wolschke, C., et al.[2018]

Rabbit-derived antithymocyte globulin (ATG) can induce a strong immune response in patients, leading to the production of antibodies against specific rabbit glycoprotein epitopes, which may compromise its effectiveness in treating conditions like type 1 diabetes.

The study found that patients developed significant levels of antibodies against these rabbit-specific epitopes after ATG treatment, suggesting that using IgGs without these xenoantigens could enhance the safety and efficacy of ATG therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-Gal and Anti-Neu5Gc Responses in Nonimmunosuppressed Patients After Treatment With Rabbit Antithymocyte Polyclonal IgGs. Salama, A., Evanno, G., Lim, N., et al.[2022]

In a study of 29 patients receiving anti-thymocyte globulin (ATG) and anti-lymphocyte globulin (ALG) for aplastic anemia, 62.1% experienced adverse effects, with fever being the most common.

ATG, which is rabbit-derived, was associated with more frequent adverse effects compared to ALG, and shorter intervals between treatment cycles increased the risk of these reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adverse effects of anti-thymocyte globulin/anti-lymphocyte globulin therapy]. Kobayashi, R., Kaneda, M., Watanabe, N., et al.[2006]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10515999/

Anti-thymocyte globulin exposure in patients with diffuse ... We aimed to explore the relationship between anti-thymocyte globulin exposure, lymphocyte reconstitution and treatment response in diffuse cutaneous systemic ...

2. ard.bmj.com ard.bmj.com/content/82/Suppl_1/1642.2

AB0857 ANTI-THYMOCYTE GLOBULIN EXPOSURE IS ... Eight (73%) responders achieved long-term remission and three (27%) responders had progressive disease in the follow-up, at a median time of eight months (IQR 5 ...

3. nature.com nature.com/articles/s41409-024-02383-3

ATG and other serotherapy in conditioning regimens for ... Association between anti-thymocyte globulin exposure and survival outcomes in adult unrelated haemopoietic cell transplantation: a ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4180909/

New Directions for Rabbit Antithymocyte Globulin ... The rATG cohort had a lower rate of CAV at 10 years post-transplant (20 % vs. 40 %; p = 0.031) but the total rATG dose was exceptionally high (20 mg/kg) [158].

5. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1634157/full

Optimizing anti-thymocyte globulin dosing in allogeneic ... They found Cday_0 ≥ 20μg/mL correlated with an approximately 3-fold reduced risk of aGVHD and 2-fold decrease in overall mortality and relapse. Their population ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03593902

Cardiac Safe Transplants for Systemic Sclerosis Anti-Thymocyte Globulin (Rabbit). Drug : Methylprednisolone. A corticosteroid medication used to suppress the immune system and decrease inflammation.

7. link.springer.com link.springer.com/article/10.1007/s40265-014-0277-6

New Directions for Rabbit Antithymocyte Globulin ... There were eight episodes of severe infection, and two cases of steroid-responsive skin GvHD with a 1-year graft survival rate of 76 %, outcomes ...