What is the mechanism of action of this treatment?

The most common treatments for Graft-versus-Host Disease (GvHD) include immunosuppressive and immunomodulatory therapies. Decidual Stromal Cells (DSC) are being studied for their potential to modulate the immune response by promoting regulatory T cells and reducing pro-inflammatory cytokines, which can help mitigate the immune attack on host tissues. This is crucial for GvHD patients as it aims to control the disease while minimizing the side effects associated with long-term immunosuppression, such as increased infection risk and organ toxicity. Effective immunomodulation can improve patient outcomes by reducing the severity and duration of GvHD episodes.

What side effects are associated with this type of intervention?

Common treatments for Graft-versus-Host Disease (GvHD) include corticosteroids, calcineurin inhibitors (like cyclosporine and tacrolimus), and biologic agents such as monoclonal antibodies. These treatments can have significant side effects. Corticosteroids can cause hyperglycemia, hypertension, osteoporosis, and increased risk of infections. Calcineurin inhibitors may lead to nephrotoxicity, hypertension, and neurotoxicity. Biologic agents can result in infusion reactions, increased susceptibility to infections, and potential reactivation of latent viruses. Decidual Stromal Cells (DSC), being studied for their immunomodulatory effects, may offer a different side effect profile, but further research is needed to fully understand their safety and efficacy.

What prior FDA approvals exist?

FDA-approved treatments for Graft-versus-Host Disease (GvHD) that focus on immunomodulation include drugs like ruxolitinib (Jakafi), which is a Janus kinase (JAK) inhibitor, and ibrutinib (Imbruvica), a Bruton's tyrosine kinase (BTK) inhibitor. These drugs work by modulating the immune response to reduce the severity of GvHD. Additionally, corticosteroids such as prednisone are commonly used as first-line treatment for GvHD due to their potent immunosuppressive effects. While Decidual Stromal Cells (DSC) are being studied for their potential long-lasting immunomodulatory effects, these FDA-approved drugs represent the current standard in immunomodulatory therapy for GvHD.

What other types of research exist?

Promising novel alternatives to Decidual Stromal Cells for GvHD treatment include: 1) Mesenchymal Stem Cells (MSCs), which have shown immunomodulatory effects and are being actively researched. 2) JAK inhibitors like ruxolitinib, which target specific pathways involved in GvHD. 3) Extracorporeal photopheresis (ECP), a procedure that modulates the immune response. 4) Regulatory T cells (Tregs) therapy, which aims to restore immune tolerance. These alternatives are currently under investigation and have shown potential in clinical trials.

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Cell Therapy

Decidual Stromal Cells for Graft-versus-Host Disease

Phase 2

Waitlist Available

Research Sponsored by University Health Network, Toronto

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Confirmed diagnosis of steroid-refractory aGvHD defined as patients administered high dose systemic corticosteroids (methylprednisolone ≥1mg/kg/day [or equivalent prednisone dose ≥1.25 mg/kg/day]), given alone or combined with calcineurin inhibitors (CNI) and either: A. Progression based on organ assessment after at least 3 days compared to organ stage at the time of initiation of high-dose systemic corticosteroid +/- CNI for the treatment of Grade II-IV aGvHD, OR B. Failure to achieve at a minimum partial response based on organ assessment after 5-7 days compared to organ stage at the time of initiation of high-dose systemic corticosteroid +/- CNI for the treatment of Grade II-IV aGvHD, OR C. Patients who fail corticosteroid taper defined as fulfilling either one of the following criteria: Requirement for an increase in the corticosteroid dose to methylprednisolone ≥1 mg/kg/day (or equivalent prednisone dose ≥1.25 mg/kg/day) OR Failure to taper the methylprednisolone dose to <0.5 mg/kg/day (or equivalent prednisone dose <0.6 mg/kg/day) for a minimum 7 days

Be older than 18 years old

Must not have

Significant respiratory disease including patients who are on mechanical ventilation or who have resting O2 saturation <90% by pulse-oximetry

Presence of severely impaired renal function defined by serum creatinine > 2 mg/dL (>176.8 μmol/L), renal dialysis requirement, or have estimated creatinine clearance <30 ml/min measured or calculated by Cockroft Gault equation (confirmed within 48h prior to study treatment start)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years, through study completion

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects may include reactions related to infusion such as fever or chills, risk of infections due to immune system suppression by the treatment, and possible organ inflammation.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

Select...

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

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I have symptoms of both acute and chronic graft-versus-host disease.

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I have had progressive multifocal leukoencephalopathy in the past.

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I am HIV positive.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years, through study completion

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years, through study completion

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years, through study completion for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

To compare the efficacy of DSC vs. Investigator's choice Best Available Therapy (BAT) in patients with Grade II-IV SR-aGvHD assessed by Durable Overall Response Rate (DOR) at Day 56

Secondary study objectives

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

To assess 1-year Non-Relapse Mortality (NRM)

To assess 1-year Overall Survival (OS)

+2 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: DSCExperimental Treatment1 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: BATActive Control1 Intervention

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

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Graft-versus-Host Disease (GvHD) include immunosuppressive and immunomodulatory therapies. Decidual Stromal Cells (DSC) are being studied for their potential to modulate the immune response by promoting regulatory T cells and reducing pro-inflammatory cytokines, which can help mitigate the immune attack on host tissues. This is crucial for GvHD patients as it aims to control the disease while minimizing the side effects associated with long-term immunosuppression, such as increased infection risk and organ toxicity. Effective immunomodulation can improve patient outcomes by reducing the severity and duration of GvHD episodes.