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

Phase 1

Terminated

• Conditions: Intestinal GVHD
• Interventions: Biological: allogeneic fecal microbiota; Drug: Ruxolitinib; Drug: Methylprednisone

• Registration Number: NCT04269850
• Lead Sponsor: St. Petersburg State Pavlov Medical University

Brief 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.

Study Timeline

• Study Start: 2019-09-01
• Study First Submitted: 2020-02-12
• Study First Submitted QC: 2020-02-13
• Study First Posted: 2020-02-17
• Status Verified: 2024-11
• Primary Completion: 2024-11-27
• Study Completion: 2024-11-27
• Last Update Submitted: 2024-11-27
• Last Update Posted: 2024-12-03

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

Inclusion Criteria

• Age 5-70 years
• Histologically confirmed gastrointestinal acute GVHD
• Grade III-IV gastrointestinal GVHD based on 2016 MAGIC criteria
• Ability for oral drug intake
• Signed informed consent

Exclusion Criteria

• Requirement for oxigen and/or vasopressor support
• Respiratory distress >grade I
• Severe organ dysfunction: AST or ALT >5 upper normal limits, bilirubin >1.5 upper normal limits, creatinine >2 upper normal limits,creatinine clearance < 60 mL/min
• Ongoing fluconazole therapy
• Any malignancy requiring systemic therapy at the time of enrollment
• Mixed chimerism at last evaluation
• Uncontrolled bacterial or fungal infection at the time of enrollment
• Requirement for vasopressor support at the time of enrollment
• Karnofsky index <30%
• Severe concurrent illness that can interfere with study procedures
• Somatic or psychiatric disorder making the patient unable to sign informed consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
FMT+ruxolitinib+steroids	allogeneic fecal microbiota	ruxolitinib 10 mg bid, fecal microbiota transplantation 2 caps/kg single dose, methylprednisone 0.5 mg/kg bid
FMT+ruxolitinib+steroids	Ruxolitinib	ruxolitinib 10 mg bid, fecal microbiota transplantation 2 caps/kg single dose, methylprednisone 0.5 mg/kg bid
FMT+ruxolitinib+steroids	Methylprednisone	ruxolitinib 10 mg bid, fecal microbiota transplantation 2 caps/kg single dose, methylprednisone 0.5 mg/kg bid

Primary Outcome Measures

Name	Time	Method
Overall survival	365 days	Time from treatment initiation to death or end of follow up

Secondary Outcome Measures

Name	Time	Method
Infectious complications	100 days	Cumulative incidence of bacterial, viral and fungal infections
Time to ruxolitinib discontinuation	365 days	Time from treatment initiation to ruxolitinib cessation without GVHD flare
Time to systemic immunosuppression discontinuation	365 days	Time from treatment initiation to cessation of all systemic immunosupression without GVHD flare
Incidence of Adverse Events based on CTC AE 5.0	100 days	Based on CTC AE 5.0
Time to steroid discontinuation	100 days	Time from treatment initiation to steroid cessation without GVHD flare
Overal response rate	100 days	Evaluated with 2009 consensus criteria and 2016 severity grading on days +7,+28, +56, +100

Trial Locations

Locations (1)

Pavlov First Saint-Petersburg State Medical University; 🇷🇺 Saint Petersburg, Russian Federation