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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial targets individuals with severe acute Graft-versus-Host Disease (a condition where donated bone marrow or stem cells attack the recipient's body) that does not respond to steroids. The trial compares the effectiveness of Decidual Stromal Cells (special cells that may help reduce immune responses) with the best available treatments chosen by doctors. Participants will receive two infusions of these cells and may receive additional infusions if necessary. Suitable candidates include those who have undergone a stem cell transplant and are not responding to high-dose steroids for their severe GvHD. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to benefit from potentially effective new therapies.

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.

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

Research has shown that Decidual Stromal Cells (DSC) might help treat severe acute Graft-versus-Host Disease (GVHD) that doesn't respond to steroids. In earlier studies, patients treated with DSC for GVHD had a one-year survival rate of 67%, surpassing previous treatments at the same center. Another study found that patients with steroid-resistant acute GVHD treated with DSC had a survival rate of 31% when using a specific type of plasma.

In a small pilot study, all 21 patients with severe GVHD responded to DSC treatment within 28 days. These results suggest that DSCs are generally safe and could be a better option for those who don't respond to standard treatments. However, while these findings are promising, they come from earlier studies, and ongoing trials will provide more information about their safety and effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for GvHD?

Researchers are excited about Decidual Stromal Cells (DSCs) for treating graft-versus-host disease (GvHD) because they offer a unique approach compared to current treatments, which typically include immunosuppressants like anti-thymocyte globulin, mTOR inhibitors, and ruxolitinib. Unlike these traditional therapies, DSCs are derived from maternal tissue and have the potential to modulate the immune system in a more targeted manner, possibly reducing the risk of severe side effects. Furthermore, DSCs can be administered in multiple doses tailored to the patient's response, which may lead to faster and more effective symptom control. This tailored and potentially safer approach makes DSCs a promising option for GvHD treatment.

What evidence suggests that Decidual Stromal Cells could be an effective treatment for Graft-versus-Host Disease?

Research has shown that Decidual Stromal Cells (DSCs), which participants in this trial may receive, can help treat severe acute graft-versus-host disease (aGvHD). In one study, all 21 patients who received DSCs improved by day 28. Another study found that 11 patients fully recovered, and 10 showed partial improvement, with 81% surviving for at least a year. These findings suggest that DSCs can manage this condition by easing symptoms and increasing survival chances. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4291217/

Treatment of Severe Chronic Graft-Versus-Host Disease with ... In this study, we investigated DSCs as a cellular therapy for chronic graft-versus-host disease (cGvHD), a severe complication after allogeneic hematopoietic ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11016840/

Placenta-Derived Decidua Stromal Cells - PubMed Central - NIH All patients responded, with a complete response of acute GVHD in 11 patients and partial response in 10 and 1-year survival of 81%. Randomized trials are ...

3. astctjournal.org astctjournal.org/article/S1083-8791(19)30359-3/fulltext

Long-Term Follow-Up of a Pilot Study Using Placenta ... All 21 patients treated for severe acute graft-versus-host disease with decidua stromal cells (DSCs) responded by day 28.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05132166?term=AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(AREA%5BConditionSearch%5D(%22Homologous%20Wasting%20Disease%22)%20AND%20AREA%5BInterventionSearch%5D(%22MTOR%20Inhibitors%22)))&rank=2

NCT05132166 | A Randomized Phase II Study to Compare ... The main purpose of this study is to compare the efficacy of Decidual Stromal Cells (DSC) with Investigators choice best available treatment (BAT). If ...

5. translational-medicine.biomedcentral.com translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04731-1

Real-world data suggest effectiveness of the allogeneic ... A recent real-world analysis of outcomes for 64 adult RR-aGvHD patients not treated with MSCs reports survival of 20%, 16% and 10% beyond 6, 12 and 24 months, ...

6. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.00795/full

Safety and Side Effects of Using Placenta-Derived ... One-year survival for the DSC patients with GVHD was 67%, which was significantly better than achieved previously at our center. One-year ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10585098/

Novel therapies for graft versus host disease with a focus on ... Furthermore, patients with steroid-refractory acute GVHD, displayed survival rates of 73% with albumin and 31% with AB plasma-supplemented DSCs, compared to the ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10664468/

Real-world data suggest effectiveness of the allogeneic ... Real-world data suggest effectiveness of the allogeneic mesenchymal stromal cells preparation MSC-FFM in ruxolitinib-refractory acute graft-versus-host disease.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT04118556

Decidua Stroma Cells for Steroid Resistent Acute Graft- ... The primary objectives will be safety and to compare durable overall response (DOR) at 56 days after randomization between patients receiving DSC with patients ...