Acute Graft Versus Host DiseasePhase 1NCT04280471

Fecal Microbiota Transplantation for the Treatment of Severe Acute Gut Graft-Versus-Host Disease

A Phase 1 study testing Fecal Microbiota Transplantation Capsule in people with Acute Graft Versus Host Disease and Gastrointestinal Tract Acute Graft Versus Host Disease, run by Jonsson Comprehensive Cancer Center at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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Trial summary

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Acute Graft Versus Host Disease, Gastrointestinal Tract Acute Graft Versus Host Disease, Severe Gastrointestinal Tract Acute Graft Versus Host Disease
What is being tested?: Fecal Microbiota Transplantation Capsule
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 0 participants
Where: 1 siteUnited States
Study dates: 1 Sep 2023to 1 Dec 2025
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 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Subjects who received an allogenic hematopoietic stem cell transplantation (HSCT)
Acute GvHD defined as experiencing GvHD symptoms starting prior to day +100 after HSCT
Gut GvHD defined as subjects experiencing GvHD symptoms consistent with stage 3 or stage 4 by Center for International Blood and Marrow Transplant Research (CIBMTR) staging:
Stage 3 acute gut GvHD subjects having 1500-1999 mL stool per day
Stage 4 subjects having greater than 2 liters of stool per day and/or severe abdominal cramping, bleeding or ileus
Steroid-refractory acute gut GVHD defined as progression of symptoms after 3 days of systemic steroids (> 1 mg/kg/day methylprednisolone) or steroid-resistant acute gut GvHD defined stable symptoms after 5 days of systemic steroids (> 1 mg/kg/day methylprednisolone)
Able to swallow capsules without aspiration or dysphagia
Ability to understand the written informed consent and the willingness to sign the consent and accept the risk of receiving unrelated donor stool

Who cannot join

Absolute neutrophil count < 500 cells/uL
Presence of recurrent Clostridium difficile infection
Presence of ileus or toxic megacolon
History of multi-drug resistant stool pathogen
History of inflammatory bowel disease (i.e Crohn's disease or ulcerative colitis)
Uncontrolled and active systemic infection from bacteria, virus or fungus

Show all 18Show fewer

Human immunodeficiency virus (HIV)-positive subjects
Quantifiable cytomegalovirus (CMV) and/or Epstein-Barr virus (EBV) evaluated by polymerase chain reaction (PCR) after hematopoietic stem cell transplantation (HSCT) and after neutrophil engraftment defined as absolute neutrophil count (ANC) > 500 cells/uL
Hemodynamically unstable
Active gastrointestinal bleed
Pregnant and/or breastfeeding women
Dysphagia due to oropharyngeal, esophageal, functional, neuromuscular (e.g. stroke, multiple sclerosis, amyotrophic lateral sclerosis [ALS]) or subject shows evidence of dysphagia when the 'safety test' capsule is administered
Delayed gastric emptying syndrome
Known chronic aspiration
Subjects with a history of significant allergy to foods
Subjects with allergies to sodium chloride, glycerol, theobroma oil, hide bovine gelatin, sodium lauryl sulfate, colorants Federal Food, Drug, and Cosmetic Act (FD\&C), or titanium dioxide, all ingredients generally recognized as safe (GRAS)
History of previous gastrointestinal surgery
Subjects who are receiving other investigational agents for treatment of gut GvHD

Trial locations and contacts

1 site in 1 country.

United States1 site

UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095

Other trials in United States

About this study

Official title: An Open-Label Phase 1 Pilot Study: Fecal Microbiota Transplantation (FMT) in Severe Acute Gut Graft-Versus-Host Disease Patients

This phase I trial studies the side effects of using an investigational procedure (fecal microbiota transplantation [FMT]) in treating patients with severe acute gut graft-versus-host-disease. The purpose of a fecal microbiota transplantation is to use feces from a healthy human donor to replace the abnormal gut bacteria in the recipient. One of the side effects of a stem cell transplant is the development of graft-versus-host disease (GvHD) in several organs including gut. GvHD is caused by the donated bone marrow or peripheral blood cells recognizing the recipient's body as foreign and attacking it. Acute gut GvHD is one of the leading causes of death after transplant. Recently, studies have shown that patients with reduced intestinal bacterial diversity in their stool during acute gut GvHD have higher overall mortality rates. The information learned from this study may offer FMT as a promising therapy for the treatment of severe acute gut graft-versus-host-disease.

Read the detailed description

PRIMARY OBJECTIVES:

For safety evaluation, episodes of microbial bloodstream infection attributed to fecal microbiota transplantation (FMT) within the first 7 days after start of each FMT administration.

II. For tolerability evaluation, subject must ingest 50% of one dose of FMT product without grade 3 or higher adverse events (AEs) within the first 7 days post-FMT.

SECONDARY OBJECTIVE:

To collect stool, oral swabs and blood specimens for future studies to define bacterial taxa diversity, microbial translocation as well as metabolomic and proteomic changes associated with the development of graft versus host disease (GvHD).

II. For clinical efficacy, > 50% of subjects with at least 1 stage of gut GvHD improvement by 8 weeks after the first dose of FMT.

OUTLINE:

Patients ingest OpenBiome FMT Capsule Dose Extended (DE) orally for two consecutive days. One dose is equivalent to the ingestion of 30 capsules and thus each day the patient will ingest 15 capsules. If no response is noted after 7 days, patients may receive a second dose of FMT for an additional 2 days. Standard treatment for gut GvHD will continue during this time.

After completion of study treatment, patients are followed for up to 6 months.

Conditions: Acute Graft Versus Host Disease, Gastrointestinal Tract Acute Graft Versus Host Disease, Severe Gastrointestinal Tract Acute Graft Versus Host Disease, Steroid Resistant Gastrointestinal Tract Acute Graft Versus Host Disease
Being tested: Fecal Microbiota Transplantation Capsule
Keywords: Gut GvHD, FMT

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Fecal Microbiota Transplantation CapsuleDrug
Also called Fecal Microbiota Preparation Delivery Capsule, FMPCapDE, FMT Capsule DE, FMT Capsule Delivery
Receive OpenBiome FMT Capsule DE PO

Study groups in NCT04280471
Study group	Role	What they receive
Treatment (OpenBiome FMT capsule DE)	Experimental	Patients ingest OpenBiome FMT Capsule Dose Extended (DE) orally for two consecutive days. One dose is equivalent to the ingestion of 30 capsules and thus each day the patient will ingest 15 capsules. If no response is noted after 7 days, patients may receive a second dose of FMT for an additional 2 days. Receives: Drug: Fecal Microbiota Transplantation Capsule

What is being measured

The primary outcome is the main question the study is designed to answer.

Incidence of adverse events
For safety evaluation, episodes of microbial bloodstream infection attributed to fecal microbiota transplantation (FMT) within the first 7 days after start of each FMT administration. For tolerability evaluation, at least 60% of subjects able to ingest 50% of one dose of FMT without grade 3 or higher adverse events (AEs) within the first 7 days post-FMT. Subjects will be monitored via assessment of gut graft versus host disease (GvHD) staging and adverse events will be performed bi-weekly for the first 4 weeks after the first dose of FMT, weekly during the hospitalization and monthly up to six months after hospital discharge.
Measured: Up to 6 months

Secondary outcomes (2)

Collection of stool, oral swabs and blood specimens to define bacterial taxa diversity, microbial translocation as well as metabolomic and proteomic changes associated with the development of graft versus host disease (GvHD)
Alpha diversity metrics will be compared between time points mixed effect regression models. Multivariate differences will be calculated using permutational multivariate analysis of variance (PERMANOVA). Differential abundance techniques will be used to compare taxa over time using DESeq2 package. DESeq2 models taxa counts with a negative binomial model. To look specifically at before and after FMT, we will apply multivariate techniques such as principal coordinate analysis (PCoA) to identify parameters that are affected positively by FMT and to determine whether these differences persist over time. The PERMNOVA technique will be applied to survey population-level differences before \& after FMT. We will use the Benjamini-Hochberg false discovery rate (FDR) to account for multiple hypothesis testing.
Measured: Up to 6 months
GvHD improvement
Clinical efficacy will be defined as > 50% of subjects with at least 1 stage of gut GvHD improvement by 8 weeks after the first dose of FMT.
Measured: Up to 8 weeks after the first dose of FMT

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Sep 20231 Dec 2025

First posted21 Feb 2020
Study start1 Sep 2023 (estimated)
Primary completion30 Dec 2024 (estimated)
Study completion1 Dec 2025 (estimated)

Why it stopped: The study was not opened

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Acute Graft Versus Host DiseaseStudies of the same condition, open and under way.
More trials run by Jonsson Comprehensive Cancer CenterThe 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: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04280471
Sponsor's protocol ID: 19-001736
Other IDs: NCI-2020-00211, 19-001736
Status last verified: Nov 2022
First submitted: 5 Feb 2020
Last updated: 22 Sep 2023
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 22 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-Label Phase 1 Pilot Study: Fecal Microbiota Transplantation (FMT) in Severe Acute Gut Graft-Versus-Host Disease Patients
ClinicalTrials.gov ID: NCT04280471
Acronym / sponsor ID: 19-001736
Conditions: Acute Graft Versus Host Disease, Gastrointestinal Tract Acute Graft Versus Host Disease, Severe Gastrointestinal Tract Acute Graft Versus Host Disease, Steroid Resistant Gastrointestinal Tract Acute Graft Versus Host Disease
Keywords: Gut GvHD, FMT
Phase: Phase 1
Study type: Interventional
Recruitment status: WithdrawnReason stopped: The study was not opened
Enrolment: 0 participants (actual)
Lead sponsor: Jonsson Comprehensive Cancer CenterUniversity, hospital or other
Study start: 1 Sep 2023 (estimated)
Primary completion: 30 Dec 2024 (estimated)
Study completion: 1 Dec 2025 (estimated)
First posted: 21 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.

Detailed description

PRIMARY OBJECTIVES:

For safety evaluation, episodes of microbial bloodstream infection attributed to fecal microbiota transplantation (FMT) within the first 7 days after start of each FMT administration.

II. For tolerability evaluation, subject must ingest 50% of one dose of FMT product without grade 3 or higher adverse events (AEs) within the first 7 days post-FMT.

SECONDARY OBJECTIVE:

To collect stool, oral swabs and blood specimens for future studies to define bacterial taxa diversity, microbial translocation as well as metabolomic and proteomic changes associated with the development of graft versus host disease (GvHD).

II. For clinical efficacy, > 50% of subjects with at least 1 stage of gut GvHD improvement by 8 weeks after the first dose of FMT.

OUTLINE:

After completion of study treatment, patients are followed for up to 6 months.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Treatment (OpenBiome FMT capsule DE)	Experimental	Drug: Fecal Microbiota Transplantation CapsulePatients ingest OpenBiome FMT Capsule Dose Extended (DE) orally for two consecutive days. One dose is equivalent to the ingestion of 30 capsules and thus each day the patient will ingest 15 capsules. If no response is noted after 7 days, patients may receive a second dose of FMT for an additional 2 days.

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Subjects who received an allogenic hematopoietic stem cell transplantation (HSCT)
Acute GvHD defined as experiencing GvHD symptoms starting prior to day +100 after HSCT
Gut GvHD defined as subjects experiencing GvHD symptoms consistent with stage 3 or stage 4 by Center for International Blood and Marrow Transplant Research (CIBMTR) staging:
Steroid-refractory acute gut GVHD defined as progression of symptoms after 3 days of systemic steroids (> 1 mg/kg/day methylprednisolone) or steroid-resistant acute gut GvHD defined stable symptoms after 5 days of systemic steroids (> 1 mg/kg/day methylprednisolone)
Able to swallow capsules without aspiration or dysphagia

Key exclusion criteria (18 listed)

Absolute neutrophil count < 500 cells/uL
Presence of recurrent Clostridium difficile infection
Presence of ileus or toxic megacolon
History of multi-drug resistant stool pathogen
History of inflammatory bowel disease (i.e Crohn's disease or ulcerative colitis)

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 Transplantation CapsuleAlso: Fecal Microbiota Preparation Delivery Capsule, FMPCapDE, FMT Capsule DE, FMT Capsule DeliveryReceive OpenBiome FMT Capsule DE PO	Drug	Treatment (OpenBiome FMT capsule DE)

Primary outcome

Incidence of adverse events
Time frame: Up to 6 months
For safety evaluation, episodes of microbial bloodstream infection attributed to fecal microbiota transplantation (FMT) within the first 7 days after start of each FMT administration. For tolerability evaluation, at least 60% of subjects able to ingest 50% of one dose of FMT without grade 3 or higher adverse events (AEs) within the first 7 days post-FMT. Subjects will be monitored via assessment of gut graft versus host disease (GvHD) staging and adverse events will be performed bi-weekly for the first 4 weeks after the first dose of FMT, weekly during the hospitalization and monthly up to six months after hospital discharge.

2 secondary outcomes

Collection of stool, oral swabs and blood specimens to define bacterial taxa diversity, microbial translocation as well as metabolomic and proteomic changes associated with the development of graft versus host disease (GvHD)
Time frame: Up to 6 months
GvHD improvement
Time frame: Up to 8 weeks after the first dose of FMT

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2023.

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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.

Grace Aldrovandi principal investigator

UCLA / Jonsson Comprehensive Cancer Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 8 inclusion and 18 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: withdrawn, as of the sponsor's last update on 22 Sep 2023. 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 was withdrawn before enrolling participants, so there are no results.

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?

Incidence of adverse events (time frame: Up to 6 months). 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 NCT04280471.

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 22 Sep 2023.