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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
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.
Pediatric Hematology and Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna
Bologna, Italy
UOC Clinica di Oncoematologia Pediatrica, Azienda Ospedale-Università Padova
Padova, Italy
Department of Hematology/Oncology, Cell and Gene Therapy, IRCCS Bambino Gesù Children's Hospital
Roma, Italy
Safety (AE and treatment-related AE, according to CTCAE v5.0)
Number of Participants With Adverse Events and Treatment-Related Adverse Events as Assessed by CTCAE v5.0
Time frame: 28 days
Efficacy: Overall Response Rate (ORR)
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).
Time frame: 28 days
Microbiota modification
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).
Time frame: 56 days
Cumulative incidence of infections
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.
Time frame: 28 days
Efficacy on other GVHD target organs
Response in skin and liver GVHD involvement according to MAGIC criteria.
Time frame: 56 days
Immune reconstitution
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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.
Time frame: 90 days