Intestinal GVHDPhase 1/2JAK-FMTNCT04269850
Fecal Microbiota Transplantation With Ruxolitinib and Steroids as an Upfront Treatment of Severe Acute Intestinal GVHD
A Phase 1/2 study testing allogeneic fecal microbiota, Ruxolitinib and Methylprednisone in people with Intestinal GVHD, run by St. Petersburg State Pavlov Medical University at 1 site in Russia.
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Intestinal GVHD
- What is being tested?
- allogeneic fecal microbiota, Ruxolitinib and Methylprednisone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteRussia
- Study dates
- 1 Sep 2019to 27 Nov 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Russia1 site
Pavlov First Saint-Petersburg State Medical University
Saint Petersburg, 197022
About this study
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
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.
Read the 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.
- Conditions
- Intestinal GVHD
- Being tested
- allogeneic fecal microbiota, Ruxolitinib, Methylprednisone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
allogeneic fecal microbiotaBiological
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.
RuxolitinibDrug
Ruxolitinib starting dose 10 mg bid. In case of grade 4 hematological toxicity dose can be reduced by 25-75%.
MethylprednisoneDrug
Methylprednisone starting dose 0.5 mg/kg bid IV or oral, with subsequent tapper by 0.1 mg/kg every 5 days.
| Study group | Role | What they receive |
|---|---|---|
| FMT+ruxolitinib+steroids | Experimental | ruxolitinib 10 mg bid, fecal microbiota transplantation 2 caps/kg single dose, methylprednisone 0.5 mg/kg bid Receives: Biological: allogeneic fecal microbiota; Drug: Ruxolitinib; Drug: Methylprednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
Time from treatment initiation to death or end of follow up
Measured: 365 days
Secondary outcomes (6)
Overal response rate
Evaluated with 2009 consensus criteria and 2016 severity grading on days +7,+28, +56, +100
Measured: 100 days
Incidence of Adverse Events based on CTC AE 5.0
Based on CTC AE 5.0
Measured: 100 days
Infectious complications
Cumulative incidence of bacterial, viral and fungal infections
Measured: 100 days
Time to steroid discontinuation
Time from treatment initiation to steroid cessation without GVHD flare
Measured: 100 days
Time to ruxolitinib discontinuation
Time from treatment initiation to ruxolitinib cessation without GVHD flare
Measured: 365 days
Time to systemic immunosuppression discontinuation
Time from treatment initiation to cessation of all systemic immunosupression without GVHD flare
Measured: 365 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2020
- Study start1 Sep 2019
- Primary completion27 Nov 2024
- Study completion27 Nov 2024
Why it stopped: Poor recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intestinal GVHDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Petersburg State Pavlov Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ivan S Moiseev, St. Petersburg State Pavlov Medical University
- Investigators
- Boris Afanasyev, Professor, Principal investigator, Pavlov First Saint Petersburg State Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04269850
- Sponsor's protocol ID
- tfm-gvhd-2019
- Acronym
- JAK-FMT
- Status last verified
- Nov 2024
- First submitted
- 12 Feb 2020
- Last updated
- 3 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04269850
- Acronym / sponsor ID
- JAK-FMT / tfm-gvhd-2019
- Conditions
- Intestinal GVHD
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor recruitment
- Enrolment
- 2 participants (actual)
- Lead sponsor
- St. Petersburg State Pavlov Medical UniversityUniversity, hospital or other
- Study start
- 1 Sep 2019 (actual)
- Primary completion
- 27 Nov 2024 (actual)
- Study completion
- 27 Nov 2024 (actual)
- First posted
- 17 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| FMT+ruxolitinib+steroids | Experimental | Biological: allogeneic fecal microbiota, Drug: Ruxolitinib, Drug: Methylprednisoneruxolitinib 10 mg bid, fecal microbiota transplantation 2 caps/kg single dose, methylprednisone 0.5 mg/kg bid |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| allogeneic fecal microbiotaSingle 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. | Biological | FMT+ruxolitinib+steroids |
| RuxolitinibRuxolitinib starting dose 10 mg bid. In case of grade 4 hematological toxicity dose can be reduced by 25-75%. | Drug | FMT+ruxolitinib+steroids |
| MethylprednisoneMethylprednisone starting dose 0.5 mg/kg bid IV or oral, with subsequent tapper by 0.1 mg/kg every 5 days. | Drug | FMT+ruxolitinib+steroids |
Primary outcome
Overall survival
Time frame: 365 days
Time from treatment initiation to death or end of follow up
6 secondary outcomes
Overal response rate
Time frame: 100 days
Incidence of Adverse Events based on CTC AE 5.0
Time frame: 100 days
Infectious complications
Time frame: 100 days
Time to steroid discontinuation
Time frame: 100 days
Time to ruxolitinib discontinuation
Time frame: 365 days
Time to systemic immunosuppression discontinuation
Time frame: 365 days
Results and safety
The study was stopped early (reason given: Poor recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2024.
- Individual participant dataSharing planned: No
Related trials for Intestinal GVHD
RecruitingPhase 1/2
FMT for Pediatric SR-aGVHD
Acute Graft Versus Host Disease in Intestine
RecruitingPhase 2
Faecal Microbiota Transplantation After Allogeneic Stem Cell Transplantation
Acute Leukemia in Remission, Myelodysplastic Syndromes
RecruitingPhase 1
Fecal Microbiota Transplant and Dietary Fiber Supplementation for the Treatment of Gut Graft Versus Host Disease
Intestinal Graft Versus Host Disease
Not yet recruitingPhase 4
Emerging Indications for Hyperbaric Oxygen Treatment
Post-COVID-19 Condition, Ulcerative Colitis
RecruitingPhase 2
Enteral Nutrition Versus Standard of Care in Allogeneic Hematopoietic Stem Cell Transplantation
Allogeneic Hematopoietic Stem Cell Transplant (Allo-HSCT)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Boris Afanasyev, Professor principal investigator
Pavlov First Saint Petersburg State Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing allogeneic fecal microbiota, Ruxolitinib and Methylprednisone in people with Intestinal GVHD, run by St. Petersburg State Pavlov Medical University at 1 site in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Poor recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (time frame: 365 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2024.