Fecal Microbiota Transplantation for Steroid-Refractory Acute GI GVHD
ConditionGraft vs Host Disease
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
AgeNot listed
SponsorChang Gung Memorial Hospital
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Stage II to IV steroid refractory acute GI-GvHD in allo-HSCT recipients
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
Resistant to a first-line therapy with corticosteroids (CS)
Lack of improvement after 5 days of treatment with CS at 2 mg/kg/d methylprednisolone or other CS with equivalent dose,
Disqualifiers
Absolute neutrophil count < 500 cells/uL.
Absolute platelet count < 30000 /uL which is not correctable by transfusion
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.
Uncontrolled and active infection from bacteria, virus, or fungus as determined by the investigators.
Trial design
Design model
Single group
Treatments tested in this trial
Fecal microbiota transplantation (FMT)
Biological/VaccineAbout 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.
Treatment groups
35 Participants
are divided into 1 treatment groupGroup A: single armExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
event-free survival
Time frame
From first fecal microbiota transplantation to the first event or up to 6 months2
overall response rate
at least one stage improvement in acute GI-GvHD
Time frame
on day-28 after first FMT3
complete response rate
improvement of acute GI-GvHD to stage 0
Time frame
on day-28 after first FMTSecondary outcomes
1
Overall response rate
at least one stage improvement in acute GI-GvHD
Time frame
on day-56 after first FMT2
Complete response rate
improvement of acute GI-GvHD to stage 0
Time frame
on day 56 after first FMT3
Time to response
Time frame
from the time of first FMT to the time of at least one stage improvement in acute GI-GvHD4
Relapse rate
Relapse defined as at least one stage acute gastrointestinal GvHD progression.
Time frame
at least two-year follow-up after first FMTOther outcomes
1
Incidence of changes in severity of endoscopic abnormalities and/or histologic evidence of acute GI GVHD relative to baseline assessment.
Gastrointestinal mucosa improvement observed by ileocolonoscopy or panendoscopy findings, or histopathology findings from gastrointestinal tract biopsy
Time frame
on second or third FMT2
Changes in GvHD related biomarkers
Time frame
on day-28 after first FMTSponsors and contacts
Click on the lead sponsor to view all of their trials.
Chang Gung Memorial Hospital
Lead sponsor
National Taiwan University Hospital
Collaborator
Source ClinicalTrials.gov