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

NCT ID: NCT04269850

Last Updated: 2024-12-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

2 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-09-01

Study Completion Date

2024-11-27

Brief Summary

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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

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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

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Intestinal GVHD

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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FMT+ruxolitinib+steroids

ruxolitinib 10 mg bid, fecal microbiota transplantation 2 caps/kg single dose, methylprednisone 0.5 mg/kg bid

Group Type EXPERIMENTAL

allogeneic fecal microbiota

Intervention Type BIOLOGICAL

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.

Ruxolitinib

Intervention Type DRUG

Ruxolitinib starting dose 10 mg bid. In case of grade 4 hematological toxicity dose can be reduced by 25-75%.

Methylprednisone

Intervention Type DRUG

Methylprednisone starting dose 0.5 mg/kg bid IV or oral, with subsequent tapper by 0.1 mg/kg every 5 days.

Interventions

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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.

Intervention Type BIOLOGICAL

Ruxolitinib

Ruxolitinib starting dose 10 mg bid. In case of grade 4 hematological toxicity dose can be reduced by 25-75%.

Intervention Type DRUG

Methylprednisone

Methylprednisone starting dose 0.5 mg/kg bid IV or oral, with subsequent tapper by 0.1 mg/kg every 5 days.

Intervention Type DRUG

Eligibility Criteria

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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
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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St. Petersburg State Pavlov Medical University

OTHER

Sponsor Role lead

Responsible Party

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Ivan S Moiseev

Deputy Director for research, Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation Affiliation: St. Petersburg State Pavlov Medical University

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Boris Afanasyev, Professor

Role: PRINCIPAL_INVESTIGATOR

Pavlov First Saint Petersburg State Medical University

Locations

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Pavlov First Saint-Petersburg State Medical University

Saint Petersburg, , Russia

Site Status

Countries

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Russia

Other Identifiers

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tfm-gvhd-2019

Identifier Type: -

Identifier Source: org_study_id