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

Intestinal GVHD Clinical Trial

— JAK-FMT  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04269850
• Other study ID #: tfm-gvhd-2019
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 1, 2019
• Est. completion date: December 1, 2025

Study information

• Verified date: November 2023
• Source: St. Petersburg State Pavlov Medical University
• Contact: Oleg Goloshchapov
• Phone: +79219792913
• Email: golocht[@]yandex.ru
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 1, 2025
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Intestinal GVHD

Intervention

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

Locations

Country	Name	City	State
Russian Federation	Pavlov First Saint-Petersburg State Medical University	Saint Petersburg

Sponsors (1)

Lead Sponsor	Collaborator
St. Petersburg State Pavlov Medical University

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	Time from treatment initiation to death or end of follow up	365 days
Secondary	Overal response rate	Evaluated with 2009 consensus criteria and 2016 severity grading on days +7,+28, +56, +100	100 days
Secondary	Incidence of Adverse Events based on CTC AE 5.0	Based on CTC AE 5.0	100 days
Secondary	Infectious complications	Cumulative incidence of bacterial, viral and fungal infections	100 days
Secondary	Time to steroid discontinuation	Time from treatment initiation to steroid cessation without GVHD flare	100 days
Secondary	Time to ruxolitinib discontinuation	Time from treatment initiation to ruxolitinib cessation without GVHD flare	365 days
Secondary	Time to systemic immunosuppression discontinuation	Time from treatment initiation to cessation of all systemic immunosupression without GVHD flare	365 days