Fecal Microbiota Transplantation for Steroid-Refractory Acute GI GVHD

Official title

Fecal Microbiota Transplantation for the Treatment of Steroid Refractory Acute Gastrointestinal Graft-Versus-Host Disease in Patients After Allogeneic Hematopoietic Stem Cell Transplantation

Overview

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

• Biological Fecal 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.

Primary outcome measures

• event-free survival [Time frame: From first fecal microbiota transplantation to the first event or up to 6 months]
• overall response rate [Time frame: on day-28 after first FMT]
• complete response rate [Time frame: on day-28 after first FMT]

Secondary outcome measures (7)

• Overall response rate [Time frame: on day-56 after first FMT]
• Complete response rate [Time frame: on day 56 after first FMT]
• Time to response [Time frame: from the time of first FMT to the time of at least one stage improvement in acute GI-GvHD]
• Relapse rate [Time frame: at least two-year follow-up after first FMT]
• Overall survival [Time frame: from the time of first FMT to the time of death.]
• Non-relapse mortality [Time frame: at least two-year follow-up after first FMT]
• Incidence of adverse events [Time frame: at least two-year follow-up after first FMT]

Eligibility criteria

Inclusion criteria

• 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)

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• Lack of improvement after 5 days of treatment with CS at 2 mg/kg/d methylprednisolone or other CS with equivalent dose,
• Progression after 3 days of treatment with CS at 2 mg/kg/d methylprednisolone or other CS with equivalent dose.
• Age ≥ 18 years old.
• Allo-HSCT with any type of donor, stem cell source, GvHD prophylaxis or conditioning regimen.
• 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.
• 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)
• 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

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Taiwan · 1 center

• Chang Gung Memorial Hospital at Linkou — Taoyuan

Identifiers

NCT: NCT07364617 · 202401777A0 · LK20250520001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗