Acute Graft-Versus-Host Disease (Gvhd) GradePhase 1NCT04139577
FMT In High-Risk Acute GVHD After ALLO HCT
A Phase 1 study testing Fecal Microbiota Transplant in people with Acute Graft-Versus-Host Disease (Gvhd) Grade and Hematopoietic Cell Transplantation, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the effectiveness of Fecal Microbiota Transplant (FMT) treatment in high-risk acute graft-versus-host disease (GVHD). This research study involves an experimental intervention called FMT. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Graft-Versus-Host Disease (Gvhd) Grade, Hematopoietic Cell Transplantation, Fecal Microbiota Transplant
- What is being tested?
- Fecal Microbiota Transplant
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Jun 2021to 5 Jan 2023
- Phase
- Phase 1
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men or women ≥ 18 years old
- Patient has undergone allogeneic hematopoietic cell transplantation from any donor (related or unrelated with any degree of HLA matching) and any donor source (bone marrow, peripheral blood stem cells, or cord blood) for a hematologic malignancy or disorder. Recipients of myeloablative and reduced-intensity conditioning regimens are eligible.
- Evidence of myeloid engraftment (eg, absolute neutrophil count ≥ 0.5 × 109/L for 3 consecutive assessments if ablative therapy was previously used). Use of growth factor supplementation is allowed.
- Patient must have clinically suspected Grade II to IV aGVHD as per MAGIC criteria. Clinical suspicion of aGVHD by the treating physician is sufficient and biopsies are not required to pathologically confirm aGVHD. However, in situations where alternative diagnoses of drug effects or infection are not adequately ruled out on clinical suspicion alone, biopsies are recommended. - Patients must have a diagnosis of high-risk acute GVHD, defined as either:
- -- Steroid-refractory GVHD:
- Progressive GVHD after at least 3 days of systemic corticosteroids (≥ 1 mg/kg/day of prednisone equivalent), OR
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- No improvement in GVHD after at least 7 days on ≥ 1 mg/kg/day of prednisone equivalent or insufficient improvement which warrants the addition of another agent, OR
- Flare of GVHD symptoms during taper.
- High-risk, treatment-naïve GVHD
- AA3 risk by Ann Arbor GVHD scoring risk system
- Treatment-naïve: less than 3 days of therapy with systemic corticosteroids (≥ 1 mg/kg/day of prednisone equivalent)
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study and for 3 months after FMT.
- Ability to understand and the willingness to sign a written informed consent document, including the willingness to accept risk of unrelated donor stool.
- Ability to swallow large capsules.
Who cannot join
- Participants who have initiated a new systemic treatment for steroid-refractory GVHD (institutional standard or investigational agent) within the 2 weeks prior to first dose of FMT. Treatment with FMT is allowed once the time since initiation of newest systemic therapy is 2 weeks or longer.
- Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Delayed gastric emptying syndrome or large hiatal hernia
- Known chronic aspiration
- Participants with a history of significant allergy to foods not excluded from the donor diet (excluded foods are tree nuts, peanuts, shellfish, eggs)
- Pregnant and breast-feeding women are ineligible because they are not eligible for hematopoietic stem cell transplantation.
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- HIV-positive participants are ineligible.
- Participants who are unable to swallow pills.
- Participants with end-stage liver disease (cirrhosis)
- Participants with acute, active gastrointestinal infection (e.g., typhlitis, diverticulitis, appendicitis)
- Participants with inflammatory bowel disease (e.g., ulcerative colitis, Crohn's)
- Prior total colectomy
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: Fecal Microbiota Transplantation (FMT) in for the Treatment of High-Risk Acute Graft-Versus-Host Disease (GVHD) After Allogeneic Hematopoietic Cell Transplantation (HCT)
The purpose of this study is to evaluate the effectiveness of Fecal Microbiota Transplant (FMT) treatment in high-risk acute graft-versus-host disease (GVHD).
This research study involves an experimental intervention called FMT.
Read the detailed description
In this research study, the investigators are evaluating the effectiveness of Fecal Microbiota Transplant (FMT) treatment in high-risk acute GVHD. The investigators are evaluating the effectiveness of FMT (also known as 'stool transplantation' or 'fecal transplant') in being able to transfer gut organisms from a healthy donor to the patient.
The investigators are also evaluating the ability of this treatment to improve or completely resolve the clinical symptoms (diarrhea, abdominal pain, rash, liver inflammation) that can occur with acute GVHD.This research study is a Pilot Study, which is the first time investigators are examining this intervention for treatment of acute GVHD.
The FDA (the U.S. Food and Drug Administration) has not approved FMT for this use. The FDA has classified human stool as a biological agent and determined that its use in FMT therapy should be regulated to ensure patient safety. To use FMT to treat recurrent Clostridium difficile infection, the most common indication for FMT, does not require an investigation new drug permit. To use FMT for research or to treat any condition other than recurrent Clostridium difficile infection requires an investigation new drug permit. An investigation new drug permit has been obtained for this study.
- After HCT, the body's microbiome (the natural existence of various bacteria and organisms) in the intestinal tract may be affected, in that the number and types of good bacteria is reduced (also called a reduction in microbial flora diversity). Studies have shown that the number and types of good bacteria in the gut can impact whether or not graft-versus-host disease (GVHD) is developed. GVHD occurs when donated bone marrow cells attack the body with an immune response.
- FMT is a process utilizing microbial components which are the good, healthy bacteria that would otherwise naturally occur the body. Since may have decreased microbial flora diversity after HCT, these microbial components are taken from a stool donor. They are extracted from fecal matter (stool) and put into a capsule to ingest.
- Conditions
- Acute Graft-Versus-Host Disease (Gvhd) Grade, Hematopoietic Cell Transplantation, Fecal Microbiota Transplant
- Being tested
- Fecal Microbiota Transplant
- Keywords
- Acute Graft-Versus-Host Disease (Gvhd) Grade, Hematopoietic Cell Transplantation, Fecal Microbiota Transplant
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fecal Microbiota TransplantBiological
Also called FMT
FMT- Oral Study Drug, predetermined dosage and timings, up to 2 cycles
| Study group | Role | What they receive |
|---|---|---|
| Fecal Microbiota Transplant (FMT) FOR HIGH-RISK ACUTE GVHD | Experimental | The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.
this research study for up to 6 months. You may receive up to 2 cycles of the study treatment.
- Fecal Microbiota Transplant ( FMT)- Oral Study Drug, predetermined dosage and timings, up to 2 cycles.
* One cycle of treatment consists of one induction week of FMT followed by three weeks of maintenance FMT.
* The maintenance weeks happen for 3 weeks after the induction week.
* All doses will be administered in the clinic.
* A second cycle of treatment as deemed appropriate Receives: Biological: Fecal Microbiota Transplant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients who are able to swallow ≥ 40 capsules (out of 75)
Based on this information, FMT will be considered feasible if, among the 11 eligible patients, ≥8 patients are able to swallow ≥ 40 capsules.
Measured: 29 Days
Secondary outcomes (4)
Response Rate-Acute GVHD
Kaplan-Meier estimates
Measured: 29 Days
Overall Survival
Kaplan-Meier estimates
Measured: 6 months, 12 Months
Progression Free Survival
Kaplan-Meier estimates
Measured: 6 months, 12 Months
Non-relapse mortality (NRM)
time from first dose of FMT to death without relapse or progression or underlying disease. Deaths from any cause without prior progression are considered as NRM events
Measured: 6 month, 12 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2019
- Study start18 Jun 2021
- Primary completion3 Aug 2022
- Study completion5 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Graft-Versus-Host Disease (Gvhd) GradeStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- American Cancer Society, Inc.
- Responsible party
- Principal investigator, Zachariah Michael DeFilipp, Massachusetts General Hospital
- Investigators
- Zachariah DeFilipp, MD, Principal investigator, Masachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04139577
- Sponsor's protocol ID
- 19-359
- Status last verified
- Mar 2024
- First submitted
- 23 Oct 2019
- Last updated
- 7 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to the Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Publications
DeFilipp Z, Damania AV, Kim HT, Chang CC, El-Jawahri A, McAfee SL, Bottoms AS, Toncheva V, Smith MM, Dolaher M, Perry L, White M, Diana B, Connolly S, Dey BR, Frigault MJ, Newcomb RA, O'Donnell PV, Spitzer TR, Mansour MK, Weber D, Ajami NJ, Hohmann E, Jenq RR, Chen YB. Third-party fecal microbiota transplantation for high-risk treatment-naive acute GVHD of the lower GI tract. Blood Adv. 2024 May 14;8(9):2074-2084. doi: 10.1182/bloodadvances.2024012556.
PubMed 38471063
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fecal Microbiota Transplantation (FMT) in for the Treatment of High-Risk Acute Graft-Versus-Host Disease (GVHD) After Allogeneic Hematopoietic Cell Transplantation (HCT)
- ClinicalTrials.gov ID
- NCT04139577
- Acronym / sponsor ID
- 19-359
- Conditions
- Acute Graft-Versus-Host Disease (Gvhd) Grade, Hematopoietic Cell Transplantation, Fecal Microbiota Transplant
- Keywords
- Acute Graft-Versus-Host Disease (Gvhd) Grade, Hematopoietic Cell Transplantation, Fecal Microbiota Transplant
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- American Cancer Society, Inc.
- Study start
- 18 Jun 2021 (actual)
- Primary completion
- 3 Aug 2022 (actual)
- Study completion
- 5 Jan 2023 (actual)
- First posted
- 25 Oct 2019 (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.
The purpose of this study is to evaluate the effectiveness of Fecal Microbiota Transplant (FMT) treatment in high-risk acute graft-versus-host disease (GVHD).
This research study involves an experimental intervention called FMT.
Detailed description
In this research study, the investigators are evaluating the effectiveness of Fecal Microbiota Transplant (FMT) treatment in high-risk acute GVHD. The investigators are evaluating the effectiveness of FMT (also known as 'stool transplantation' or 'fecal transplant') in being able to transfer gut organisms from a healthy donor to the patient.
The investigators are also evaluating the ability of this treatment to improve or completely resolve the clinical symptoms (diarrhea, abdominal pain, rash, liver inflammation) that can occur with acute GVHD.This research study is a Pilot Study, which is the first time investigators are examining this intervention for treatment of acute GVHD.
The FDA (the U.S. Food and Drug Administration) has not approved FMT for this use. The FDA has classified human stool as a biological agent and determined that its use in FMT therapy should be regulated to ensure patient safety. To use FMT to treat recurrent Clostridium difficile infection, the most common indication for FMT, does not require an investigation new drug permit. To use FMT for research or to treat any condition other than recurrent Clostridium difficile infection requires an investigation new drug permit. An investigation new drug permit has been obtained for this study.
- After HCT, the body's microbiome (the natural existence of various bacteria and organisms) in the intestinal tract may be affected, in that the number and types of good bacteria is reduced (also called a reduction in microbial flora diversity). Studies have shown that the number and types of good bacteria in the gut can impact whether or not graft-versus-host disease (GVHD) is developed. GVHD occurs when donated bone marrow cells attack the body with an immune response.
- FMT is a process utilizing microbial components which are the good, healthy bacteria that would otherwise naturally occur the body. Since may have decreased microbial flora diversity after HCT, these microbial components are taken from a stool donor. They are extracted from fecal matter (stool) and put into a capsule to ingest.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Fecal Microbiota Transplant (FMT) FOR HIGH-RISK ACUTE GVHD | Experimental | Biological: Fecal Microbiota TransplantThe research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. this research study for up to 6 months. You may receive up to 2 cycles of the study treatment. - Fecal Microbiota Transplant ( FMT)- Oral Study Drug, predetermined dosage and timings, up to 2 cycles. * One cycle of treatment consists of one induction week of FMT followed by three weeks of maintenance FMT. * The maintenance weeks happen for 3 weeks after the induction week. * All doses will be administered in the clinic. * A second cycle of treatment as deemed appropriate |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Men or women ≥ 18 years old
- Patient has undergone allogeneic hematopoietic cell transplantation from any donor (related or unrelated with any degree of HLA matching) and any donor source (bone marrow, peripheral blood stem cells, or cord blood) for a hematologic malignancy or disorder. Recipients of myeloablative and reduced-intensity conditioning regimens are eligible.
- Evidence of myeloid engraftment (eg, absolute neutrophil count ≥ 0.5 × 109/L for 3 consecutive assessments if ablative therapy was previously used). Use of growth factor supplementation is allowed.
- Patient must have clinically suspected Grade II to IV aGVHD as per MAGIC criteria. Clinical suspicion of aGVHD by the treating physician is sufficient and biopsies are not required to pathologically confirm aGVHD. However, in situations where alternative diagnoses of drug effects or infection are not adequately ruled out on clinical suspicion alone, biopsies are recommended. - Patients must have a diagnosis of high-risk acute GVHD, defined as either:
- High-risk, treatment-naïve GVHD
Key exclusion criteria (12 listed)
- Participants who have initiated a new systemic treatment for steroid-refractory GVHD (institutional standard or investigational agent) within the 2 weeks prior to first dose of FMT. Treatment with FMT is allowed once the time since initiation of newest systemic therapy is 2 weeks or longer.
- Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Delayed gastric emptying syndrome or large hiatal hernia
- Known chronic aspiration
- Participants with a history of significant allergy to foods not excluded from the donor diet (excluded foods are tree nuts, peanuts, shellfish, eggs)
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 |
|---|---|---|
| Fecal Microbiota TransplantAlso: FMTFMT- Oral Study Drug, predetermined dosage and timings, up to 2 cycles | Biological | Fecal Microbiota Transplant (FMT) FOR HIGH-RISK ACUTE GVHD |
Primary outcome
Proportion of patients who are able to swallow ≥ 40 capsules (out of 75)
Time frame: 29 Days
Based on this information, FMT will be considered feasible if, among the 11 eligible patients, ≥8 patients are able to swallow ≥ 40 capsules.
4 secondary outcomes
Response Rate-Acute GVHD
Time frame: 29 Days
Overall Survival
Time frame: 6 months, 12 Months
Progression Free Survival
Time frame: 6 months, 12 Months
Non-relapse mortality (NRM)
Time frame: 6 month, 12 Months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2024.
- Derived from this study: PubMed 38471063DeFilipp Z, Damania AV, Kim HT, Chang CC, El-Jawahri A, McAfee SL, Bottoms AS, Toncheva V, Smith MM, Dolaher M, Perry L, White M, Diana B, Connolly S, Dey BR, Frigault MJ, Newcomb RA, O'Donnell PV, Spitzer TR, Mansour MK, Weber D, Ajami NJ, Hohmann E, Jenq RR, Chen YB. Third-party fecal microbiota transplantation for high-risk treatment-naive acute GVHD of the lower GI tract. Blood Adv. 2024 May 14;8(9):2074-2084. doi: 10.1182/bloodadvances.2024012556.
- Individual participant dataSharing planned: Yes. The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to the Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
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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.
Zachariah DeFilipp, MD principal investigator
Masachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Fecal Microbiota Transplant in people with Acute Graft-Versus-Host Disease (Gvhd) Grade and Hematopoietic Cell Transplantation, run by Massachusetts General Hospital at 1 site in United States.
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 14 inclusion and 12 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: finished, as of the sponsor's last update on 7 Mar 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 United States. 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 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.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Proportion of patients who are able to swallow ≥ 40 capsules (out of 75) (time frame: 29 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04139577, which also lists 1 linked publication.
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 7 Mar 2024.