Decidual Stromal Cells for Graft-versus-Host Disease

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must be taking: Corticosteroids, Calcineurin inhibitors

Must not be taking: Other aGvHD treatments

Disqualifiers: Chronic GvHD, Uncontrolled infection, HIV, 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: 2

Duration: 8 weeks

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment using special cells from the uterus lining to help patients with severe GvHD who don't get better with steroids. The goal is to see if these cells can reduce inflammation and improve their condition.

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current medications. You can continue standard treatments for GvHD, including systemic corticosteroids and other immune suppressive therapies, as per your doctor's guidance.

What data supports the effectiveness of the treatment Decidual Stromal Cells for Graft-versus-Host Disease?

Research shows that decidual stromal cells (DSCs) can help treat severe acute graft-versus-host disease (GVHD) by creating an anti-inflammatory environment, which reduces harmful immune responses. In studies, DSCs have shown promise in treating GVHD, with some patients experiencing complete resolution of symptoms and others showing partial improvement. ^{1 2 3 4 5}

Is it safe to use decidual stromal cells in humans?

Decidual stromal cells (DSCs) appear to be safe for use in humans, with studies showing no significant adverse effects during or after infusion. Some patients experienced mild, temporary reactions, but overall, DSCs were well-tolerated in clinical trials for conditions like graft-versus-host disease. ^{1 2 3 5 6}

How is the treatment with decidual stromal cells different from other treatments for graft-versus-host disease?

Decidual stromal cells (DSCs) are unique because they are derived from the placenta and have strong immunosuppressive properties, which help reduce the immune response causing graft-versus-host disease. Unlike other treatments, DSCs are administered as a cellular therapy, and they have shown promise in treating patients who do not respond to standard steroid treatments. ^{1 3 4 5 7}

Eligibility Criteria

This trial is for adults over 18 who've had a stem cell transplant and are now facing severe acute Graft versus Host Disease (GvHD) that hasn't improved with steroids. They should not have HIV, severely impaired kidney function, or be pregnant. Also, they can't join if they've been treated with other drugs for GvHD apart from steroids or have an uncontrolled infection.

Inclusion Criteria

My condition did not improve after high-dose steroid treatment for aGvHD.

I have acute GvHD after a stem cell transplant and need treatment.

I have had a stem cell transplant from any donor using various sources.

Exclusion Criteria

I have severe lung problems and need help breathing or my oxygen levels are usually below 90%.

My kidney function is severely impaired, indicated by high creatinine levels or I require dialysis.

I do not have an active infection that is getting worse despite treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Decidual Stromal Cells (DSC) or Best Available Treatment (BAT) for steroid-resistant severe acute GvHD

8 weeks

At least 2 visits (in-person) for DSC arm, additional visits depending on response

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Long-term follow-up

Participants are monitored for long-term outcomes such as overall survival and incidence of infections

up to 5 years

Treatment Details

Interventions

• Decidual Stromal Cells

Trial Overview The study compares the effectiveness of Decidual Stromal Cells (DSC) against the best available treatments like anti-thymocyte globulin and others for severe acute GvHD. Participants will receive DSC infusions in their veins at least one week apart, possibly up to four doses depending on how well they respond.

Participant Groups

Group I: DSC Experimental Treatment 1 Intervention

The dose will be 1×106 DSC/kg bodyweight, at least 2 doses at least one week apart. Within the first 28 days, patients meeting criteria of aGvHD disease progression, mixed response or no response, may be given additional weekly doses of DSC until satisfactory response (ie: CR) are reached (max 4 doses in total).

Group II: BAT Active Control 1 Intervention

anti-thymocyte globulin (ATG), extracorporeal photopheresis (ECP), mTOR inhibitors (everolimus or sirolimus), vedolizumab, ruxolitinib.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

References

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

Xeno-immunosuppressive properties of human decidual stromal cells in mouse models of alloreactivity in vitro and in vivo. [2021]

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

Potential and challenges of placenta-derived decidua stromal cell therapy in inflammation-associated disorders. [2022]

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

Treatment of severe chronic graft-versus-host disease with decidual stromal cells and tracing with (111)indium radiolabeling. [2022]

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

Placenta-Derived Decidua Stromal Cells for Treatment of Severe Acute Graft-Versus-Host Disease. [2019]

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

Long-Term Follow-Up of a Pilot Study Using Placenta-Derived Decidua Stromal Cells for Severe Acute Graft-versus-Host Disease. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Side Effects of Using Placenta-Derived Decidual Stromal Cells for Graft-versus-Host Disease and Hemorrhagic Cystitis. [2019]

7. Denmark pubmed.ncbi.nlm.nih.gov

Decidua as a site of extrathymic V gamma I T-cell differentiation. [2019]