Clinical Trials for Acute Graft Versus Host Disease

This article provides information about 9 ongoing clinical trials studying treatments for acute graft versus host disease, a condition that can occur after stem cell or bone marrow transplantation. The trials are testing various medications including mesenchymal stromal cells, investigational drugs like RLS-0071 and apraglutide, and cell-based therapies. These studies are being conducted across multiple European countries including Germany, Spain, France, Italy, Poland, Lithuania, Sweden, and the Netherlands.

Clinical trial locations

• France
  • Study on Mesenchymal Stromal Cells (MC0518) for Treating Steroid-Resistant Acute Graft Versus Host Disease in Adults and Adolescents
  • Study on the Effectiveness and Safety of CYP-001 and Corticosteroids for Adults with High-Risk Acute Graft Versus Host Disease
  • Study on the Effectiveness of Mesenchymal Stromal Cells in Children with Steroid-Refractory Acute Graft-Versus-Host Disease
• Germany
  • Study of RLS-0071 Treatment for Hospitalized Patients with Steroid-Resistant Acute Graft-versus-Host Disease (aGvHD)
  • Study on Mesenchymal Stromal Cells (MC0518) for Treating Steroid-Resistant Acute Graft Versus Host Disease in Adults and Adolescents
  • Study on the Effectiveness of Mesenchymal Stromal Cells in Children with Steroid-Refractory Acute Graft-Versus-Host Disease
  • Study on the Safety of ATreg Cells for Patients with Leukemia After Stem Cell Transplant to Reduce Graft vs Host Disease
  • Study of RLS-0071 in Hospitalized Patients with Steroid-Resistant Acute Graft-versus-Host Disease (aGvHD)
  • Study on Long-Term Safety of Ruxolitinib, Panobinostat, and Siremadlin for Patients Continuing Treatment from Previous Studies
  • Study on the Safety and Effectiveness of Apraglutide for Patients with Steroid-Resistant Gastrointestinal Acute Graft Versus Host Disease
• Italy
  • Study on the Effectiveness and Safety of CYP-001 and Corticosteroids for Adults with High-Risk Acute Graft Versus Host Disease
  • Study on the Effectiveness of Mesenchymal Stromal Cells in Children with Steroid-Refractory Acute Graft-Versus-Host Disease
  • Study on Long-Term Safety of Ruxolitinib, Panobinostat, and Siremadlin for Patients Continuing Treatment from Previous Studies
• Lithuania
  • Study on the Effectiveness and Safety of CYP-001 and Corticosteroids for Adults with High-Risk Acute Graft Versus Host Disease
• Netherlands
  • Comparison of Tacrolimus alone versus Tacrolimus, Mycophenolate mofetil and Prednisone combination in elderly kidney transplant patients to reduce infections
• Poland
  • Study on Mesenchymal Stromal Cells (MC0518) for Treating Steroid-Resistant Acute Graft Versus Host Disease in Adults and Adolescents
  • Study on the Effectiveness of Mesenchymal Stromal Cells in Children with Steroid-Refractory Acute Graft-Versus-Host Disease
  • Study on Long-Term Safety of Ruxolitinib, Panobinostat, and Siremadlin for Patients Continuing Treatment from Previous Studies
• Spain
  • Study of RLS-0071 Treatment for Hospitalized Patients with Steroid-Resistant Acute Graft-versus-Host Disease (aGvHD)
  • Study on Mesenchymal Stromal Cells (MC0518) for Treating Steroid-Resistant Acute Graft Versus Host Disease in Adults and Adolescents
  • Study on the Effectiveness and Safety of CYP-001 and Corticosteroids for Adults with High-Risk Acute Graft Versus Host Disease
  • Study on the Effectiveness of Mesenchymal Stromal Cells in Children with Steroid-Refractory Acute Graft-Versus-Host Disease
  • Study of RLS-0071 in Hospitalized Patients with Steroid-Resistant Acute Graft-versus-Host Disease (aGvHD)
• Sweden
  • Study on Long-Term Safety of Ruxolitinib, Panobinostat, and Siremadlin for Patients Continuing Treatment from Previous Studies

Comparison of Tacrolimus alone versus Tacrolimus, Mycophenolate mofetil and Prednisone combination in elderly kidney transplant patients to reduce infections

This study focuses on elderly kidney transplant recipients and examines immunosuppression approaches. Participants must be 60 years or older and receiving either a deceased or living donor kidney transplant without donor-specific antibodies present at the time of transplantation. Previous kidney transplant recipients may participate if they meet all other requirements.

Patients are excluded if they are younger than 18 or older than 65 years, have previous non-kidney organ transplants, active or chronic infections, current pregnancy or breastfeeding, known allergies to immunosuppressive medications, severe heart, liver or lung disease, active cancer or cancer history within the past 5 years, uncontrolled diabetes, mental conditions affecting study compliance, participation in other trials within 30 days, substance abuse history within 2 years, severe kidney dysfunction despite transplantation, or recent organ rejection episodes.

The study compares single-drug therapy with tacrolimus against the standard triple therapy combining tacrolimus, mycophenolate mofetil, and prednisone. The primary goal is to determine whether using fewer medications can reduce infection risks and improve quality of life in older transplant recipients. Researchers will monitor kidney function, infection occurrence, and overall patient well-being throughout a three-year follow-up period after transplantation.

The investigational approach tests tacrolimus as a single-drug therapy, which works by suppressing the immune system to prevent organ rejection. This is being compared to the standard combination of three immunosuppressive medications traditionally used after kidney transplantation.

Study of RLS-0071 Treatment for Hospitalized Patients with Steroid-Resistant Acute Graft-versus-Host Disease (aGvHD)

This trial evaluates a new treatment for patients with steroid-refractory acute graft-versus-host disease occurring after stem cell transplantation. Participants must be at least 12 years old, weigh between 40 and 140 kilograms, be hospitalized with the condition, have adequate blood counts without growth factor support, have recovered from stem cell transplantation with neutrophil counts above specific thresholds, and maintain specific liver function and blood clotting parameters.

Exclusion criteria include age below 12 or above 75 years, severe organ dysfunction, active uncontrolled infections, recent participation in other trials, known allergic reactions to similar medications, pregnancy or breastfeeding, use of interfering medications, uncontrolled blood pressure, recent cancer history except successfully treated skin cancer, inability to follow procedures, mental conditions affecting participation, and active bleeding disorders.

The study tests RLS-0071 given through intravenous infusion for up to 14 days, combined with standard treatment. Researchers monitor symptom improvement, particularly affecting the skin, liver, and digestive system, tracking changes for up to 180 days after starting treatment. The focus is on determining both safety and effectiveness of this medication.

RLS-0071 is an investigational medication being studied for treating acute graft versus host disease in patients who haven’t responded to steroid treatment. The study aims to understand its safety profile and optimal dosing strategy.

Study on Mesenchymal Stromal Cells (MC0518) for Treating Steroid-Resistant Acute Graft Versus Host Disease in Adults and Adolescents

This study focuses on steroid-refractory acute graft-versus-host disease in patients following stem cell transplantation. Participants must have undergone allogeneic hematopoietic stem cell transplantation, been diagnosed with Grade II to IV acute graft versus host disease, experienced failure of first-line steroid treatment, be at least 12 years old weighing at least 15 kilograms, have estimated life expectancy exceeding 28 days, and agree to use appropriate contraceptive methods during the trial.

The trial excludes patients who have responded to steroid treatment, those without acute graft versus host disease diagnosis, individuals outside the specified age range, those unable to follow study procedures, pregnant or breastfeeding women, patients with interfering medical conditions, current participants in other trials, those with severe allergic reaction history to study medications, and patients with uncontrolled serious infections.

The study compares MC0518, consisting of mesenchymal stromal cells that help reduce inflammation and support healing, against the best available therapy currently used for managing this condition. Participants are randomly assigned to receive either the new treatment or existing therapies, with monitoring at specific intervals including days 28, 60, 100, and 180 to assess response and overall survival.

MC0518 is a cell-based therapy administered through intravenous infusion, designed to modulate immune responses and promote tissue repair by interacting with various immune cells in patients with steroid-refractory acute graft versus host disease.

Study on the Effectiveness and Safety of CYP-001 and Corticosteroids for Adults with High-Risk Acute Graft Versus Host Disease

This trial studies high-risk acute graft versus host disease occurring after stem cell transplantation. Eligible participants must be 18 years or older, provide written consent, have received their first allogeneic hematopoietic stem cell transplant from any donor source, be clinically diagnosed with acute graft versus host disease requiring systemic corticosteroid therapy, meet specific clinical features of high-risk disease within 72 hours before enrollment, show evidence of myeloid engraftment with sustained neutrophil counts, have life expectancy of at least one month, and demonstrate understanding of the study requirements.

The study compares CYP-001, made from allogeneic mesenchymoangioblast-derived mesenchymal stem cells combined with corticosteroids, against corticosteroids with placebo. Participants are randomly assigned to treatment groups and monitored at intervals including days 7, 14, 21, 28, 60, and 100 to observe overall response, which includes symptom improvement or resolution without requiring additional treatments.

The main goal is observing overall response rate by day 28, with additional tracking of response durability, overall survival, event-free survival, and failure-free survival to understand long-term treatment effects. The study continues until December 2025 with ongoing monitoring for any long-term effects or changes in condition.

CYP-001 is an investigational medication administered intravenously, currently being studied for its effectiveness in treating high-risk acute graft versus host disease. It works by modulating the immune response to reduce inflammation and tissue damage, classified as an immunomodulatory agent.

Study on the Effectiveness of Mesenchymal Stromal Cells in Children with Steroid-Refractory Acute Graft-Versus-Host Disease

This trial focuses on children and adolescents with steroid-refractory acute graft-versus-host disease following stem cell transplantation. Participants must have undergone previous allogeneic hematopoietic stem cell transplantation, been diagnosed with Grade II to IV acute graft versus host disease, experienced failure of first-line treatment, be between 28 days and 18 years old weighing at least 3.2 kilograms, have estimated life expectancy exceeding 28 days, agree to use effective contraceptive methods if applicable, and have informed consent from parents or legal guardians.

Exclusion criteria include patients without steroid-refractory acute graft-versus-host disease diagnosis, those outside the specified age range, and patients not part of the selected vulnerable population for the study.

The study compares MC0518, using mesenchymal stromal cells that reduce inflammation and support healing, against the best available therapy which may include medications like infliximab, anti-T lymphocyte immunoglobulin, methoxsalen, ruxolitinib, or etanercept. These treatments are administered through different routes including intravenous infusion or oral intake depending on the specific medication.

Participants are assessed at various intervals including days 8, 15, 22, 28, 60, 100, and 180 to evaluate overall response, with long-term monitoring continuing up to 24 months to assess survival, chronic graft-versus-host disease incidence, adverse events, and quality of life using specialized pediatric assessments.

Study on the Safety of ATreg Cells for Patients with Leukemia After Stem Cell Transplant to Reduce Graft vs Host Disease

This study evaluates the safety and tolerability of GP120-activated regulatory T cells in patients following haematopoietic stem cell transplantation. Participants must be adults aged 18 or older of any gender, willing to provide written informed consent, have a healthy third-party donor available, meet all requirements for stem cell transplantation with planned transplant from peripheral blood or bone marrow, have a well-matched donor, have blood-related cancer requiring transplant including acute myeloid leukemia, myelodysplastic syndromes, acute lymphoblastic leukemia, multiple myeloma, myeloproliferative neoplasms, or lymphoma, and have life expectancy exceeding six weeks.

Exclusion criteria include other serious interfering health conditions, pregnancy or breastfeeding, recent major surgery, current participation in another trial, history of allergic reactions to similar treatments, active uncontrolled infection, history of substance abuse, and inability to follow study procedures.

The treatment involves using GP120-activated regulatory T cells designed to reduce the incidence and severity of acute graft versus host disease. These special immune cells are delivered through infusion directly into the bloodstream. The study monitors participants for serious side effects at intervals including 24 hours, 3 days, 7 days, and 14 days after receiving the treatment, with continued monitoring at days 28, 56, 90, and 6 months.

Throughout the study, researchers track changes in blood components and observe effects on acute graft versus host disease incidence and severity, as well as potential infections or cancer relapses, gathering comprehensive data on the treatment’s long-term effects over six months.

Study of RLS-0071 in Hospitalized Patients with Steroid-Resistant Acute Graft-versus-Host Disease (aGvHD)

This study examines patients with acute graft versus host disease following stem cell transplantation. Eligible participants must be at least 12 years old, weigh between 40 and 140 kilograms, show blood recovery after transplantation with neutrophil counts above 500 per microliter for at least three consecutive measurements, maintain neutrophil counts above this threshold at screening without growth factor support, provide written informed consent, communicate effectively with study team, agree to use effective birth control if applicable, have steroid-resistant acute graft versus host disease, have Grade II-IV disease affecting skin, liver, or digestive system, be hospitalized or being admitted, be able to stay in hospital for at least one week, be starting or have recently started ruxolitinib treatment unless unsuitable, and be able to start study medication within 48 hours of starting ruxolitinib.

Exclusion criteria include age below 12 or above 75 years, severe organ dysfunction, active uncontrolled infections, recent trial participation, known allergic reactions to similar medications, pregnancy or breastfeeding, use of interfering medications, uncontrolled blood pressure or unstable vital signs, recent cancer history except successfully treated skin cancer, inability to follow procedures, mental conditions affecting participation, and active bleeding disorders.

The study tests RLS-0071 given through intravenous infusion for up to 14 days in combination with standard treatments including ruxolitinib. Monitoring occurs at days 7, 14, 28, 56, and 180 after treatment initiation, checking changes in condition particularly involving skin, liver, and digestive system, with assessments of pain levels, food tolerance, and overall well-being.

The main evaluation focuses on response at day 28, with continued monitoring through day 180 to track overall health, survival, and ability to reduce other medications, especially steroids. The study aims to determine optimal dosing and establish safety profile for this investigational medication.

Study on Long-Term Safety of Ruxolitinib, Panobinostat, and Siremadlin for Patients Continuing Treatment from Previous Studies

This trial evaluates long-term safety of treatments for patients previously participating in studies involving ruxolitinib, either alone or combined with other drugs. Eligible participants must be currently enrolled in a Novartis or Incyte sponsored study, receiving treatment with ruxolitinib alone or in combination with panobinostat, siremadlin, or rineterkib, have met all requirements of the original study, and be benefiting from treatment as determined by the investigator. The study accepts both male and female patients from different age groups including children, teenagers, and adults.

Exclusion criteria include patients outside the specified age range, those not meeting specific disease criteria outlined in the parent protocol, those not part of the specified clinical trial group, and those considered part of vulnerable populations requiring special protection or care.

Participants continue their treatment with ruxolitinib or its combinations with panobinostat, siremadlin, or rineterkib, all administered orally. The study monitors frequency and severity of side effects or adverse events occurring during treatment, with regular assessments to determine any clinical benefits from continued treatment.

The research aims to provide valuable data on long-term safety of these medications and combinations for future patients. Scheduled visits allow investigators to assess clinical benefits and monitor participants until the study concludes in September 2027.

Study on the Safety and Effectiveness of Apraglutide for Patients with Steroid-Resistant Gastrointestinal Acute Graft Versus Host Disease

This trial investigates acute graft versus host disease affecting the gastrointestinal tract that doesn’t respond to standard steroid treatments. Participants must sign informed consent, be at least 12 years old weighing minimum 40 kilograms (18 and older in Germany and France), have undergone allogeneic stem cell transplant from any donor source, show evidence of myeloid and platelet engraftment with specific blood cell counts, have clinical diagnosis of lower gastrointestinal acute graft versus host disease at a specific stage with tests ruling out other diarrhea causes, have steroid-refractory lower gastrointestinal disease meeting specific criteria, be treated with steroids and ruxolitinib with ruxolitinib starting at the same time or up to 72 hours before apraglutide, and agree to use highly effective birth control methods during the trial and specified periods after treatment ends.

Exclusion criteria include patients without acute graft versus host disease, those not experiencing steroid-refractory lower gastrointestinal disease, those outside specified age range, inability to follow procedures, other interfering medical conditions, pregnancy or breastfeeding, and participation in another interfering trial.

The study tests apraglutide, a powder mixed into solution and given as injection under the skin, evaluating its safety and effectiveness. Participants receive either apraglutide or placebo in addition to current best available therapy. Regular check-ups throughout the study track progress and potential side effects, with monitoring continuing until August 2025.

Apraglutide is administered as an injection under the skin and works by mimicking a natural hormone influencing gut function, potentially reducing inflammation and promoting healing. It is classified as a glucagon-like peptide-2 analog, targeting specific receptors in the body.

Summary

The nine clinical trials presented demonstrate significant research activity focused on treating acute graft versus host disease, particularly in cases that don’t respond to standard steroid treatments. Germany leads in trial availability with seven trials, followed by Spain with five trials, reflecting strong research infrastructure in these countries for transplantation medicine.

Several trials focus on innovative cell-based therapies, particularly mesenchymal stromal cells, which appear in multiple studies testing their effectiveness in both adult and pediatric populations. The investigational drug RLS-0071 is being tested in two separate trials across Spain and Germany, indicating particular research interest in this medication for steroid-refractory cases.

The trials span different patient populations, from children as young as 28 days old to elderly adults, with specialized studies focusing on specific age groups such as elderly kidney transplant recipients and pediatric patients. Most trials require hospitalization and involve monitoring periods extending from several months to up to two years, reflecting the serious nature of the condition and need for careful long-term assessment.

Common themes across trials include focus on steroid-refractory disease, combination with standard therapies like ruxolitinib, and comprehensive monitoring of multiple organ systems particularly affecting skin, liver, and gastrointestinal tract. The diversity of approaches being tested, from cell therapies to novel pharmaceutical compounds, suggests active exploration of multiple treatment strategies for this challenging complication of stem cell transplantation.