Clinical trial NCT04269850: Fecal Microbiota Transplantation With Ruxolitinib and Steroids as an Upfront Treatment of Severe Acute Intestinal GVHD
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Intestinal GVHD
Lead sponsor: St. Petersburg State Pavlov Medical University
Sponsor class: OTHER
First posted: 2020-02-17
Enrollment: 2
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall survival
timeFrame: 365 days
Secondary outcomes:
measure: Overal response rate
timeFrame: 100 days
measure: Incidence of Adverse Events based on CTC AE 5.0
timeFrame: 100 days
measure: Infectious complications
timeFrame: 100 days
measure: Time to steroid discontinuation
timeFrame: 100 days
measure: Time to ruxolitinib discontinuation
timeFrame: 365 days
measure: Time to systemic immunosuppression discontinuation
timeFrame: 365 days
Other outcomes:
Locations:
city: Saint Petersburg
country: Russian Federation
facility: Pavlov First Saint-Petersburg State Medical University
Study officials:
affiliation: Pavlov First Saint Petersburg State Medical University
name: Boris Afanasyev, Professor
role: PRINCIPAL_INVESTIGATOR
References: