Graft vs Host Disease
Conditions
Keywords
Acute Gastrointestinal Graft-versus-Host Disease, fecal microbiota transplantation, steroid-refractory
Brief summary
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for various hematologic diseases. However, one of the major challenges of allo-HSCT is the occurrence of graft-versus-host disease (GvHD), particularly acute gastrointestinal GvHD (GI-GvHD). GvHD occurs when donor T cells recognize the recipient's tissue as foreign and mount an immune attack against it. Acute GI-GvHD is a common complication following allo-HSCT and a significant cause of mortality. If the initial steroid treatment for acute GvHD fails, mortality rates can reach as high as 81%. Recent studies have shown a strong association between reduced gut microbiota diversity and high mortality in patients with acute GI-GvHD, highlighting the critical role of the gut microbiome in regulating immune responses and maintaining intestinal homeostasis. Consequently, fecal microbiota transplantation (FMT) has emerged as a potential therapeutic strategy aimed at restoring a healthy gut microbiome and improving clinical outcomes in patients with acute GI-GvHD. This study aims to evaluate the efficacy and safety of FMT in patients with steroid-refractory or steroid-resistant acute GI-GvHD. The findings of this research will contribute to establishing FMT as a potential and effective treatment option for managing severe acute GI-GvHD, thereby improving patient outcomes and reducing transplant-related mortality.
Detailed description
This is a prospective, single-arm, open-label, phase II clinical trial evaluating the safety and efficacy of fecal microbiota transplantation (FMT) in adult patients with steroid-refractory acute gastrointestinal graft-versus-host disease (acute GI-GvHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Eligible patients will receive 250 cc microbiota fluid prepared from healthy screened donors, delivered into the terminal ileum or cecum via ileocolonoscopy, or into the terminal duodenum via panendoscopy. The study aims to assess event-free survival, overall and complete response rates, survival outcomes, changes in steroid exposure, adverse events, and microbiological/immunological biomarkers. A total of 35 participants will be enrolled over a planned 2-year study period.
Interventions
BIOLOGICALFecal microbiota transplantation (FMT)
About 250 mL microbiota fluid, containing approximately 60 cm³ of stool materials; 6x10¹³ bacteria, will be delivered to the terminal ileum/cecum via ileocolonoscopy or to the duodenum via panendoscopy, with a second FMT given 7-21 days later and an optional third dose based on response.
Sponsors
Chang Gung Memorial Hospital
National Taiwan University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This prospective, single-arm, open-label phase II study evaluates fecal microbiota transplantation (FMT) as treatment for adults with steroid-refractory stage II-IV acute gastrointestinal graft-versus-host disease (GI-GvHD) after allogeneic hematopoietic stem cell transplantation. Participants receive 250 mL microbiota fluid delivered to the terminal ileum/cecum via ileocolonoscopy or to the duodenum via panendoscopy, with a second FMT given 7-21 days later and an optional third dose based on response. The study assesses event-free survival, overall and complete response rates at Days 28 and 56, steroid reduction, relapse, survival, and safety including infections and procedure-related complications. Serial clinical, microbiologic, and immunologic evaluations are performed to characterize treatment effects and adverse events. Total planned enrollment is 35 patients.
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. Stage II to IV steroid refractory acute GI-GvHD in allo-HSCT recipients 1. Stage II to IV acute GI-GVHD subjects, having \>1000 mL stool per day, diarrhea \> 5 times/day, or abdominal cramping, bleeding or ileus, AND 2. Resistant to a first-line therapy with corticosteroids (CS) <!-- --> 1. Lack of improvement after 5 days of treatment with CS at 2 mg/kg/d methylprednisolone or other CS with equivalent dose, 2. Progression after 3 days of treatment with CS at 2 mg/kg/d methylprednisolone or other CS with equivalent dose. 2. Age ≥ 18 years old. 3. Allo-HSCT with any type of donor, stem cell source, GvHD prophylaxis or conditioning regimen. 4. Allow vancomycin-resistant enterococcus (VRE) colonization and asymptomatic cytomegalovirus (CMV) viremia, which is defined as a detectable CMV viral load in plasma but without tissue-invasive disease. 5. Patients able to have a minimum of 12 hours discontinuation of systemic antibiotics in order to perform the allogeneic FMT (antiviral and antifungal agents are allowed) 6. Signature of informed and written consent by the subject or by the subject's legally acceptable representative for patients under guardianship or trusteeship. Subject must understand and voluntarily sign an informed consent form prior to any study-related assessments/procedures being conducted.
Exclusion criteria
1. Absolute neutrophil count \< 500 cells/uL. 2. Absolute platelet count \< 30000 /uL which is not correctable by transfusion 3. Hemodynamically unstable status with the following conditions: systolic blood pressure \< 90 mm Hg, pulse oximeter oxygen saturation (SpO2) \< 90%, PaO2 \< 60 mm Hg, or respiratory rate \> 22/minute. 4. Uncontrolled and active infection from bacteria, virus, or fungus as determined by the investigators.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| event-free survival | From first fecal microbiota transplantation to the first event or up to 6 months | — |
| overall response rate | on day-28 after first FMT | at least one stage improvement in acute GI-GvHD |
| complete response rate | on day-28 after first FMT | improvement of acute GI-GvHD to stage 0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate | on day-56 after first FMT | at least one stage improvement in acute GI-GvHD |
| Complete response rate | on day 56 after first FMT | improvement of acute GI-GvHD to stage 0 |
| Time to response | from the time of first FMT to the time of at least one stage improvement in acute GI-GvHD | — |
| Relapse rate | at least two-year follow-up after first FMT | Relapse defined as at least one stage acute gastrointestinal GvHD progression. |
| Overall survival | from the time of first FMT to the time of death. | — |
| Non-relapse mortality | at least two-year follow-up after first FMT | death without prior acute gastrointestinal GvHD relapse |
| Incidence of adverse events | at least two-year follow-up after first FMT | adverse events include but not limited to infection, cytopenia, viral reactivation, gastrointestinal bleeding, bowel rupture |
Countries
Taiwan
Contacts
CONTACTHsiao-Wen Kao, M.D.
CONTACTTung-Lian Lin, M.D.
PRINCIPAL_INVESTIGATORHsiao-Wen KAO, M.D.
Chang Gung Memorial Hospital
Outcome results
None listed