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

NCT04269850 | Terminated Phase 1

• 1 other identifier: tfm-gvhd-2019
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Intestinal GVHD

Outcome Measures

Primary Outcomes (1)

• Overall survival

  Time from treatment initiation to death or end of follow up

  365 days

Secondary Outcomes (6)

• Overal response rate

  100 days

• Incidence of Adverse Events based on CTC AE 5.0

  100 days

• Infectious complications

  100 days

• Time to steroid discontinuation

  100 days

• Time to ruxolitinib discontinuation

  365 days

Study Arms (1)

FMT+ruxolitinib+steroids

EXPERIMENTAL

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

Biological: allogeneic fecal microbiota; Drug: Ruxolitinib; Drug: Methylprednisone

Interventions

allogeneic fecal microbiota 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.

FMT+ruxolitinib+steroids

Ruxolitinib DRUG

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

FMT+ruxolitinib+steroids

Methylprednisone DRUG

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

FMT+ruxolitinib+steroids

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• St. Petersburg State Pavlov Medical University: lead

Study Sites (1)

Pavlov First Saint-Petersburg State Medical University

Saint Petersburg, 197022, Russia

Location

MeSH Terms

Interventions

ruxolitinib

Study Officials

• Boris Afanasyev, Professor

  Pavlov First Saint Petersburg State Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy Director for research, Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation Affiliation: St. Petersburg State Pavlov Medical University

Study Record Dates

• First Submitted: February 12, 2020
• First Posted: February 17, 2020
• Study Start: September 1, 2019
• Primary Completion: November 27, 2024
• Study Completion: November 27, 2024
• Last Updated: December 3, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)