Dendritic Cells for Graft-versus-Host Disease

Recruiting at 1 trial location

Overseen By Caroline Bumb

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Disqualifiers: Hepatitis B, Hepatitis C, HTLV, HIV, pregnancy

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how dendritic cells in the skin affect graft-versus-host disease (GVHD), a condition that can occur after a bone marrow transplant. Researchers aim to understand how these cells might influence the development and progression of both acute and chronic forms of skin GVHD. Participants will undergo skin biopsies to study these cells and the immune responses they trigger. The trial seeks individuals with a current or suspected diagnosis of acute or chronic skin GVHD. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could enhance understanding and treatment of skin GVHD.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that using dendritic cells (DCs) to treat graft-versus-host disease (GVHD) is actively being explored. These cells have shown promise in managing immune responses. Studies suggest that DCs might help control GVHD rather than cause harm.

Regarding safety, research on DCs in similar situations has not reported major safety concerns. As a natural part of the immune system, these cells are generally well-tolerated. However, like any treatment, side effects or unexpected reactions can occur. Each person's health and immune system should be considered when assessing risks.

As this treatment is in a clinical trial, its safety is still under study. Reaching this phase indicates existing evidence supporting its potential safety in humans. Participants can feel reassured by the careful attention to detail and safety checks in place. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using dendritic cells to treat acute and chronic skin graft versus host disease (GVHD) because these cells offer a new way to modulate the immune system. Unlike standard treatments like steroids and immunosuppressive drugs that broadly dampen immune activity, dendritic cells specifically help regulate the immune response more precisely, potentially reducing side effects. This targeted approach might improve patient outcomes by promoting tolerance and reducing the severity of GVHD without the broad immune suppression that can lead to infections and other complications.

What evidence suggests that dendritic cells might be an effective treatment for skin GVHD?

Research has shown that dendritic cells (DCs) play a crucial role in the body's immune system, particularly in conditions like graft-versus-host disease (GVHD). This trial will examine the role of dendritic cells in both acute and chronic skin GVHD. Studies have found that a low number of certain DCs, such as plasmacytoid dendritic cells, can predict the development of chronic GVHD. This suggests that dendritic cells might help control or even prevent GVHD by influencing the immune system's response after a transplant. Additionally, acute GVHD has been linked to dysfunction in DCs, affecting the activation of T cells (a type of white blood cell). Although the exact role of different DC types in skin GVHD remains unclear, their involvement in immune system regulation offers a promising avenue for treatment. ^{1 3 6 7 8}

Who Is on the Research Team?

Eynav Klechevsky, Ph.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

Inclusion Criteria

Willing and able to sign the informed consent

Current diagnosis/suspected diagnosis of acute skin GVHD OR Current diagnosis/suspected diagnosis of chronic skin GVHD

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients undergo skin biopsies and peripheral blood collection for research purposes, with optional additional biopsies on day 5-7 and day 28

4 weeks

Multiple visits for biopsies and blood collection

Follow-up

Participants are monitored for dendritic cell and lymphocyte characteristics in skin and blood samples

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Dendritic Cells

How Is the Trial Designed?

Group I: Arm 2: Chronic skin GVHD Experimental Treatment 2 Interventions

* When clinically indicated, patients will undergo a skin biopsy to confirm a suspected diagnosis of acute or chronic GVHD, or to assess the status of their previously diagnosed acute or chronic GVHD. After the necessary samples are obtained for optimal medical care of the patient, two 6 mm punch biopsies (or four 4 mm punch biopsies) will be performed for research purposes, one (or two) of the affected area and one (or two) of a non-affected area (normal skin). * Patients who have clinical resolution of their acute or chronic GVHD will undergo one additional 6 mm punch biopsy (or two additional 4 mm punch biopsies) of the previously affected area. This additional biopsy should occur within 10 cm of the previous affected area sample. * With each skin biopsy, peripheral blood will be obtained by venipuncture or cannulation of an indwelling venous access device. * Two optional skin biopsies. One on day 5-7 of treatment and one on day 28 from the start of treatment.

Group II: Arm 1: Acute skin GVHD Experimental Treatment 2 Interventions

* When clinically indicated, patients will undergo a skin biopsy to confirm a suspected diagnosis of acute or chronic GVHD, or to assess the status of their previously diagnosed acute or chronic GVHD. After the necessary samples are obtained for optimal medical care of the patient, two 6 mm punch biopsies (or four 4 mm punch biopsies) will be performed for research purposes, one (or two) of the affected area and one (or two) of a non-affected area (normal skin). * Patients who have clinical resolution of their acute or chronic GVHD will undergo one additional 6 mm punch biopsy (or two additional 4 mm punch biopsies) of the previously affected area. This additional biopsy should occur within 10 cm of the previous affected area sample. * With each skin biopsy, peripheral blood will be obtained by venipuncture or cannulation of an indwelling venous access device. * Two optional skin biopsies. One on day 5-7 of treatment and one on day 28 from the start of treatment.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3369606/

Dendritic cells and regulation of graft-versus-host disease and ... Skin GVHD has been associated with decreased human LC engraftment. However, this is thought to be a secondary effect related to steroid treatment and GVHD ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2666636723011016

A Multiparameter Prognostic Risk Score of Chronic Graft ... A low number of plasmacytoid dendritic cells at 3 months is predictive of cGVHD. •. Both biomarkers can be combined with previous acute GVHD in a ...

3. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.00093/full

Dendritic Cell Regulation of Graft-Vs.-Host Disease Acute GVHD results in a severe DC defect that prevents T-cell priming and leads to fulminant cytomegalovirus disease in mice. Blood (2015) 126:1503–14. doi ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8847139/

Established and Emerging Treatments of Skin GvHD - PMC This review summarizes the most recent advances in underlying pathomechanisms, clinical trials and newly approved agents for GvHD, with a special focus on skin ...

5. ashpublications.org ashpublications.org/blood/article/125/4/606/33872/How-we-treat-chronic-graft-versus-host-disease

How we treat chronic graft-versus-host disease | Blood He developed acute GVHD of the skin and gut, which resolved after treatment with steroid cream and oral beclomethasone and budesonide. Because malignant cells ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2666636724004329

Cutaneous Chronic Graft-Versus-Host Disease: Clinical ... Cutaneous chronic graft-versus-host disease (cGVHD) is associated with morbidity, mortality, and impaired quality of life after hematopoietic stem cell ...

7. bloodcancerunited.org bloodcancerunited.org/blood-cancer-care/adults/types-blood-cancer-treatment/stem-cell-transplantation/allogeneic/graft-versus-host-disease-gvhd

Graft-versus-host disease (GVHD) Patients with grade 3/4 acute GVHD tend to have poorer outcomes and decreased survival. Treatment for acute GVHD. Patients who develop stage 1 mild skin-only ...

8. ashpublications.org ashpublications.org/blood/article/127/25/3117/35181/Preclinical-models-of-acute-and-chronic-graft

Preclinical models of acute and chronic graft-versus-host ... In this review we discuss different prophylactic and therapeutic approaches against aGVHD and cGVHD that have been developed in preclinical models.