NCT04269850

Fecal Microbiota Transplantation With Ruxolitinib and Steroids as an Upfront Treatment of Severe Acute Intestinal GVHD

Pilot Study of Fecal Microbiota Transplantation in Combination With Ruxolitinib and Steroids for Severe Acute Intestinal Graft-versus-host-disease After Allogeneic Hematopoietic Stem Cell Transplantation

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 2 (actual)
• Sponsor: St. Petersburg State Pavlov Medical University · Academic / Other
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

Summary

Therapy of severe intestinal graft-versus-host disease (GVHD) despite the introduction of novel target agents is associated with worse outcome compared to the other forms. Response to steroids is observed only in about 10% of patients. The most promising approaches are JAK inhibition and fecal microbiota transplantation. In this pilot study we evaluate this combination treatment in the first line.

Detailed description

Acute intestinal GVHD grade III-IV after allogeneic stem cell transplantation the form with low effectiveness of corticosteroids. Despite high response rate to systemic immunosupressive agents, long term survival in this group is poor due to recurrent septic episodes and gut colonization with multidrug resistant bacteria. Fecal microbiota transplantation (FMT) from a healthy allogeneic donor, allows to restore numerous local and systemic microbiota functions, including immunomodulation and thus to reduce/stop the manifestations of GVHD. The therapeutic mechanism of action of FMT is based on competition for nutrients between obligate and pathologic bacterial strains, direct growth inhibition of the pathological pathogens, host immune system modulation, especially T-reg homeostasis, through interaction with the normal microbiota.In this pilot trial we combine FMT with ruxolitinib and steroids, one of the most effective option for refractory GVHD.

Conditions

• Intestinal GVHD

Interventions

Type	Name	Description
BIOLOGICAL	allogeneic fecal microbiota	Single dose of capsules with fecal transplant (capsules for adults - 400-815mg, for adolescents - 280-500mg, for children - 160-320mg) - 2 capsules/kg body weight, divided in two consecutive days Additional supportive therapy after FMT include omeprazole 40mg po, inulin 1gr x 4 times a day po, metoclopramide 40mg po.
DRUG	Ruxolitinib	Ruxolitinib starting dose 10 mg bid. In case of grade 4 hematological toxicity dose can be reduced by 25-75%.
DRUG	Methylprednisone	Methylprednisone starting dose 0.5 mg/kg bid IV or oral, with subsequent tapper by 0.1 mg/kg every 5 days.

Timeline

• Start date: 2019-09-01
• Primary completion: 2024-11-27
• Completion: 2024-11-27
• First posted: 2020-02-17
• Last updated: 2024-12-03

Locations

1 site across 1 country: Russia