Acute Graft Versus Host Disease in Intestine
Conditions
Keywords
graft-versus-host disease
Brief summary
This is a pilot, prospective, non-profit, multicenter, uncontrolled, open-label study to evaluate the safety and feasibility of FMT in patients aged between 3 months and 25 years suffering from acute intestinal GVHD resistant to conventional steroid therapy. Eligible patients will receive 1-3 FMT via naso-jejunal tube or endoscopy.
Interventions
BIOLOGICALFecal Microbial Transplantation
The administration of the fecal preparation (from a related donor or a third party donor) will be carried out via esophagogastroduodenoscopy, with the release of the fecal preparation into the duodenum; or via a nasoduodenal tube, with the release of the fecal preparation into the duodenum at a 'dose' of 7-12 ml/kg, up to a maximum of 250 ml/administration; or via colonoscopy. In the latter case, mucosal biopsies will not be performed to reduce the risk of bacterial translocation. In some subjects, the possibility of administering the emulsion via ENEMA will be evaluated. Cases will be selected based on specific clinical indications. In the case of a partial response, after evaluating the risk/benefit ratio, a second infusion can be performed after 3 days. The procedure can be repeated a third time later (7 days) in case of a new flare of intestinal GVHD after initial improvement.
Sponsors
Bambino Gesù Hospital and Research Institute
IRCCS Azienda Ospedaliero-Universitaria di Bologna
University Hospital, Padua, Italy
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Months to 25 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of hematological disease, malignant or non-malignant; * Patients undergoing allogeneic stem cell transplantation from a familial or unrelated donor; * Presence of acute GVHD with intestinal involvement (grade II-IV), steroid-resistant (i.e., with progression after 3 days of high-dose steroid therapy (methylprednisolone \> 2 mg/kg), no response after 7 days, progression during steroid tapering, or failure to achieve remission on day 28 from the start of steroid therapy), for those who have no indication for other second- or third-line therapies; * Signed informed consent.
Exclusion criteria
* Presence of concurrent bacterial infections requiring systemic antibiotic therapy; * Positivity for anti-HIV or anti-HCV antibodies, or for HbsAg with HBV-DNA positive by PCR; * Presence of severe mucositis; * History of chronic inflammatory bowel disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety (AE and treatment-related AE, according to CTCAE v5.0) | 28 days | Number of Participants With Adverse Events and Treatment-Related Adverse Events as Assessed by CTCAE v5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: Overall Response Rate (ORR) | 28 days | Number of participants with Complete Response (CR, defined as a score of 0 for the aGvHD grading in all evaluable organs that indicates complete resolution of all signs and symptoms of aGvHD in all evaluable organs without administration of additional systemic therapy for any earlier progression, mixed response or non-response of aGvHD) or Partial Response (PR, defined as improvement of 1 stage in 1 or more organs involved with aGvHD signs or symptoms without progression in other organs or sites without administration of additional systemic therapy for an earlier progression, mixed response or non-response of aGvHD) at day +28 according to MAGIC criteria (ORR=CR+PR). |
| Microbiota modification | 56 days | Comparison of alpha-diversity (according to Chao And Simpson indexes) and of beta-diversity (according to Bray-Curtis and UniFrac dissimilarity indexes) of patient samples taken before and after FMT (16s sequencing). |
| Cumulative incidence of infections | 28 days | Cumulative incidence of clinically-relevant infections (i.e., ≥ grade 3 according to CTCAE v 5.0) after FMT; relapse or start of a new immunosuppressive treatment will be considered competing events. |
| Efficacy on other GVHD target organs | 56 days | Response in skin and liver GVHD involvement according to MAGIC criteria. |
| Immune reconstitution | 90 days | Number of participants with CD3+ counts \> 500/mcl at day +90 after treatment. Number of participants with CD4+ counts \> 50/mcl at day +90 after treatment. |
Countries
Italy
Contacts
CONTACTPietro Merli, MD
Outcome results
None listed