Graft-versus-host Disease PreventionPhase 2NCT03862079
Fecal Transplant +/- Gut Decontamination in Preventing Acute Graft Versus Host Disease in Patients Given Broad-Spectrum Antibiotics
A Phase 2 study testing Best Practice, Fecal Microbiota Transplantation and Nystatin in people with Graft-versus-host Disease Prevention, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase II trial studies how well a fecal microbiota transplant with or without total gut decontamination works in preventing graft versus host disease in patients exposed to broad-spectrum antibiotics. Read more about this study
- Who is it for?
- Ages 16 to 75 years
- Conditions the study is for
- Graft-versus-host Disease Prevention
- What is being tested?
- Best Practice, Fecal Microbiota Transplantation and Nystatin
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2020to 31 Dec 2021
- Phase
- Phase 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 16 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients who are day -10 pre- to day +30 post-allogeneic hematopoietic cell transplant (AHCT) from any donor or graft source and for any conditioning regimen
- Patients who have received treatment with meropenem or piperacillin-tazobactam (pip-tazo) intravenously (IV) (of at least 24 hours duration) in past 7 days
- Controlled infection defined as hemodynamically stable and not requiring supplemental oxygen of more than 2 liters via nasal cannula
- Patients who are able to take oral medications in suspension form
- Patients who are able to provide informed consent (IC) and comply with all study visits and procedures
Who cannot join
- Patients who are anticipated to require continued broad spectrum antibiotics with meropenem or pip-tazo IV for > 96 hours post-engraftment such as for known, documented infections necessitating prolonged treatment
- Patients with a prior documented infection with mycormycetes
- Patients who are greater than 2 days from time of neutrophil engraftment post AHCT
- Patients with active enteric infections
- Patients with acute GVHD >= grade II
- Patients unwilling or unable to undergo the FMT via retention enema procedure
Show all 9Show fewer
- Patients who have received treatment with an investigational agent within 2 weeks of enrollment
- Patients unable to tolerate oral decontamination regimen of pip-tazo and nystatin due to prior allergy or intolerance of these medications
- Patients with any medical or psychological condition that, in the opinion of the investigator, might interfere with the subject's participation in the trial, pose any additional risk for the subject, or confound the assessments of the subject
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized Phase II Trial of Total Gut Decontamination Followed by Fecal Microbiota Transplant (FMT), FMT-Alone or Standard of Care for Reduction in Acute Graft-Versus-Host Disease of the Gastrointestinal Tract in Patients Given Broad-Spectrum Antibiotics
This phase II trial studies how well a fecal microbiota transplant with or without total gut decontamination works in preventing graft versus host disease in patients exposed to broad-spectrum antibiotics. Fecal microbiota transplantation is the administration by enema of fecal matter (stool) that includes helpful bacteria from a normal, healthy donor. Total gut decontamination uses antibiotics to remove/reduce the amount of bacteria in the digestive system. It is not yet known if a fecal microbiota transplant with or without total gut decontamination works better in preventing graft versus host disease compared to standard immunosuppressive therapies (therapies that lower the normal function of the immune system).
Read the detailed description
PRIMARY OBJECTIVES:
- To estimate the proportion of patients who develop acute graft-versus-host disease (GVHD) of the gastrointestinal (GI) tract by day 100 post-transplant for patients randomized to the standard of care, total gut decontamination (TGD) followed by fecal microbiota transplant (fecal microbiota transplantation [FMT]) and FMT alone arms.
SECONDARY OBJECTIVES:
- Overall maximum stage of lower GI tract GVHD by day 100 post-transplant. II. Cumulative incidence of acute GVHD grade II-IV and maximum grade through 6 months.
III. Time to onset of acute GVHD and acute GI GVHD. IV. Incidence of adverse events and serious adverse events. V. Incidence of bacterial blood stream infections through 6 months. VI. Hematologic recovery (neutrophils and platelets). VII. Characterization of the intestinal microbiota at enrollment, pre-FMT / time of engraftment, 2 month post-FMT/ engraftment, onset of gastrointestinal tract (GIT) GVHD, and at study completion (6 months).
VIII. Relapse-free survival at 6 months post-randomization. IX. Non-relapse mortality at 6 months post-randomization. X. Overall survival (OS) at 6 months post-randomization.
OUTLINE: Patients are randomized to 1 of 3 arms.
ARM A (TGD + FMT): Patients receive piperacillin-tazobactam orally (PO) three times daily (TID) and nystatin PO four times daily (QID) until FMT. Patients undergo stem cell transplantation on day 0, then undergo FMT via enema over 5-10 minutes within 3 weeks after transplantation.
ARM B (FMT): Patients undergo stem cell transplantation on day 0, then undergo FMT via enema over 5-10 minutes within 3 weeks after transplantation.
ARM C (STANDARD THERAPY): Patients receive standard of care.
After completion of study treatment, patients are followed up at 100 days and 6 months.
- Conditions
- Graft-versus-host Disease Prevention
- Being tested
- Best Practice, Fecal Microbiota Transplantation, Nystatin, Piperacillin-Tazobactam
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Best PracticeOther
Also called standard of care, standard therapy
Given standard of care
Fecal Microbiota TransplantationProcedure or surgery
Also called Fecal Material Transplantation, Fecal Transplantation, FMT, Poo Transplant
Undergo FMT
NystatinDrug
Also called Mycostatin, Nystex
Given PO
Piperacillin-TazobactamDrug
Also called PIPER/TAZO, Piperacillin/Tazobactam, Zosyn
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Arm I (TGD + FMT) | Experimental | Patients receive piperacillin-tazobactam PO TID and nystatin QID. Patients undergo stem cell transplantation on day 0, then undergo FMT via enema over 5-10 minutes within 3 weeks after transplantation. Receives: Procedure: Fecal Microbiota Transplantation; Drug: Nystatin; Drug: Piperacillin-Tazobactam |
| Arm II (FMT) | Experimental | Patients undergo stem cell transplantation on day 0, then undergo FMT via enema over 5-10 minutes within 3 weeks after transplantation. Receives: Procedure: Fecal Microbiota Transplantation |
| Arm III (standard therapy) | Active comparator | Patients receive standard of care. Receives: Other: Best Practice |
What is being measured
The primary outcome is the main question the study is designed to answer.
Development of acute gastrointestinal (GI) graft versus host disease (GVHD)
Summary statistics, including mean, median, range, and standard deviation, will be provided for continuous variables. Frequency tables will be used to summarize categorical variables.
Measured: Within 100 days from time of transplant
Relapse-free survival
Relapse is defined by either morphological or cytogenetic evidence of acute leukemia or myelodysplastic syndrome (MDS) inconstant with pre-transplant features, or radiologic evidence of lymphoma, documented or not by biopsy. The distribution of time-to-event endpoints, as well as the median and 90% confidence interval, will be estimated using the Kaplan-Meier method.
Measured: At 6 months post-randomization
Secondary outcomes (9)
Microbiome diversity
Will be measured using the inverse Simpson index. Summary statistics, including mean, median, range, and standard deviation, will be provided for continuous variables. Frequency tables will be used to summarize categorical variables.
Measured: At 2 weeks post fecal microbiota transplantation (FMT) (or engraftment for control arm)
Overall maximum stage of lower GI tract GVHD
Will be defined as the proportion of patients who do not develop GI GVHD within 100 days post-transplant and will be monitored simultaneously in cohorts of 5 patients separately in each arm using the approach of Thall, Simon, and Estey.
Measured: Within 100 days post-transplant
Cumulative incidence of acute GVHD grade II-IV and maximum grade
Summary statistics, including mean, median, range, and standard deviation, will be provided for continuous variables. Frequency tables will be used to summarize categorical variables.
Measured: Up to 6 months
Incidence of adverse and serious adverse events
Defined as the proportion of patients who develop blood stream infections caused by enteric bacteria within 60 days of FMT. Will be monitored simultaneously in cohorts of 5 patients separately in each arm using the approach of Thall, Simon, and Estey.
Measured: Within 60 days of FMT
Incidence of bacterial blood stream infections
Will identify those caused by a potential enteric pathogen. Summary statistics, including mean, median, range, and standard deviation, will be provided for continuous variables. Frequency tables will be used to summarize categorical variables.
Measured: Up to 6 months
Hematologic recovery (neutrophils and platelets)
Summary statistics, including mean, median, range, and standard deviation, will be provided for continuous variables. Frequency tables will be used to summarize categorical variables.
Measured: Up to 6 months
Characterization of the intestinal microbiota
Summary statistics, including mean, median, range, and standard deviation, will be provided for continuous variables. Frequency tables will be used to summarize categorical variables.
Measured: Baseline up to 6 months
Non-relapse mortality
Relapse is defined by either morphological or cytogenetic evidence of acute leukemia or MDS inconstant with pre-transplant features, or radiologic evidence of lymphoma, documented or not by biopsy. The distribution of time-to-event endpoints, as well as the median and 90% confidence interval, will be estimated using the Kaplan-Meier method.
Measured: At 6 months post-randomization
Overall survival
The distribution of time-to-event endpoints, as well as the median and 90% confidence interval, will be estimated using the Kaplan-Meier method.
Measured: At 6 months post-randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2019
- Study start1 Jun 2020 (estimated)
- Primary completion31 Dec 2021 (estimated)
- Study completion31 Dec 2021 (estimated)
Why it stopped: Per PI's request
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graft-versus-host Disease PreventionStudies of the same condition, open and under way.
- More trials run by M.D. Anderson 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Amin M Alousi, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03862079
- Sponsor's protocol ID
- 2017-0466
- Other IDs
- NCI-2019-01045, 2017-0466, P30CA016672
- Status last verified
- Mar 2020
- First submitted
- 1 Mar 2019
- Last updated
- 4 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase II Trial of Total Gut Decontamination Followed by Fecal Microbiota Transplant (FMT), FMT-Alone or Standard of Care for Reduction in Acute Graft-Versus-Host Disease of the Gastrointestinal Tract in Patients Given Broad-Spectrum Antibiotics
- ClinicalTrials.gov ID
- NCT03862079
- Acronym / sponsor ID
- 2017-0466
- Conditions
- Graft-versus-host Disease Prevention
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Per PI's request
- Enrolment
- 0 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 1 Jun 2020 (estimated)
- Primary completion
- 31 Dec 2021 (estimated)
- Study completion
- 31 Dec 2021 (estimated)
- First posted
- 5 Mar 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.
This phase II trial studies how well a fecal microbiota transplant with or without total gut decontamination works in preventing graft versus host disease in patients exposed to broad-spectrum antibiotics. Fecal microbiota transplantation is the administration by enema of fecal matter (stool) that includes helpful bacteria from a normal, healthy donor. Total gut decontamination uses antibiotics to remove/reduce the amount of bacteria in the digestive system. It is not yet known if a fecal microbiota transplant with or without total gut decontamination works better in preventing graft versus host disease compared to standard immunosuppressive therapies (therapies that lower the normal function of the immune system).
Detailed description
PRIMARY OBJECTIVES:
- To estimate the proportion of patients who develop acute graft-versus-host disease (GVHD) of the gastrointestinal (GI) tract by day 100 post-transplant for patients randomized to the standard of care, total gut decontamination (TGD) followed by fecal microbiota transplant (fecal microbiota transplantation [FMT]) and FMT alone arms.
SECONDARY OBJECTIVES:
- Overall maximum stage of lower GI tract GVHD by day 100 post-transplant. II. Cumulative incidence of acute GVHD grade II-IV and maximum grade through 6 months.
III. Time to onset of acute GVHD and acute GI GVHD. IV. Incidence of adverse events and serious adverse events. V. Incidence of bacterial blood stream infections through 6 months. VI. Hematologic recovery (neutrophils and platelets). VII. Characterization of the intestinal microbiota at enrollment, pre-FMT / time of engraftment, 2 month post-FMT/ engraftment, onset of gastrointestinal tract (GIT) GVHD, and at study completion (6 months).
VIII. Relapse-free survival at 6 months post-randomization. IX. Non-relapse mortality at 6 months post-randomization. X. Overall survival (OS) at 6 months post-randomization.
OUTLINE: Patients are randomized to 1 of 3 arms.
ARM A (TGD + FMT): Patients receive piperacillin-tazobactam orally (PO) three times daily (TID) and nystatin PO four times daily (QID) until FMT. Patients undergo stem cell transplantation on day 0, then undergo FMT via enema over 5-10 minutes within 3 weeks after transplantation.
ARM B (FMT): Patients undergo stem cell transplantation on day 0, then undergo FMT via enema over 5-10 minutes within 3 weeks after transplantation.
ARM C (STANDARD THERAPY): Patients receive standard of care.
After completion of study treatment, patients are followed up at 100 days and 6 months.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm I (TGD + FMT) | Experimental | Procedure: Fecal Microbiota Transplantation, Drug: Nystatin, Drug: Piperacillin-TazobactamPatients receive piperacillin-tazobactam PO TID and nystatin QID. Patients undergo stem cell transplantation on day 0, then undergo FMT via enema over 5-10 minutes within 3 weeks after transplantation. |
| Arm II (FMT) | Experimental | Procedure: Fecal Microbiota TransplantationPatients undergo stem cell transplantation on day 0, then undergo FMT via enema over 5-10 minutes within 3 weeks after transplantation. |
| Arm III (standard therapy) | Active comparator | Other: Best PracticePatients receive standard of care. |
Who may qualify
- Ages
- 16 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Patients who are day -10 pre- to day +30 post-allogeneic hematopoietic cell transplant (AHCT) from any donor or graft source and for any conditioning regimen
- Patients who have received treatment with meropenem or piperacillin-tazobactam (pip-tazo) intravenously (IV) (of at least 24 hours duration) in past 7 days
- Controlled infection defined as hemodynamically stable and not requiring supplemental oxygen of more than 2 liters via nasal cannula
- Patients who are able to take oral medications in suspension form
- Patients who are able to provide informed consent (IC) and comply with all study visits and procedures
Key exclusion criteria (9 listed)
- Patients who are anticipated to require continued broad spectrum antibiotics with meropenem or pip-tazo IV for > 96 hours post-engraftment such as for known, documented infections necessitating prolonged treatment
- Patients with a prior documented infection with mycormycetes
- Patients who are greater than 2 days from time of neutrophil engraftment post AHCT
- Patients with active enteric infections
- Patients with acute GVHD >= grade II
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 |
|---|---|---|
| Best PracticeAlso: standard of care, standard therapyGiven standard of care | Other | Arm III (standard therapy) |
| Fecal Microbiota TransplantationAlso: Fecal Material Transplantation, Fecal Transplantation, FMT, Poo TransplantUndergo FMT | Procedure or surgery | Arm I (TGD + FMT), Arm II (FMT) |
| NystatinAlso: Mycostatin, NystexGiven PO | Drug | Arm I (TGD + FMT) |
| Piperacillin-TazobactamAlso: PIPER/TAZO, Piperacillin/Tazobactam, ZosynGiven PO | Drug | Arm I (TGD + FMT) |
Primary outcome
Development of acute gastrointestinal (GI) graft versus host disease (GVHD)
Time frame: Within 100 days from time of transplant
Summary statistics, including mean, median, range, and standard deviation, will be provided for continuous variables. Frequency tables will be used to summarize categorical variables.
Relapse-free survival
Time frame: At 6 months post-randomization
Relapse is defined by either morphological or cytogenetic evidence of acute leukemia or myelodysplastic syndrome (MDS) inconstant with pre-transplant features, or radiologic evidence of lymphoma, documented or not by biopsy. The distribution of time-to-event endpoints, as well as the median and 90% confidence interval, will be estimated using the Kaplan-Meier method.
9 secondary outcomes
Microbiome diversity
Time frame: At 2 weeks post fecal microbiota transplantation (FMT) (or engraftment for control arm)
Overall maximum stage of lower GI tract GVHD
Time frame: Within 100 days post-transplant
Cumulative incidence of acute GVHD grade II-IV and maximum grade
Time frame: Up to 6 months
Incidence of adverse and serious adverse events
Time frame: Within 60 days of FMT
Incidence of bacterial blood stream infections
Time frame: Up to 6 months
Hematologic recovery (neutrophils and platelets)
Time frame: Up to 6 months
Characterization of the intestinal microbiota
Time frame: Baseline up to 6 months
Non-relapse mortality
Time frame: At 6 months post-randomization
Overall survival
Time frame: At 6 months post-randomization
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 4 Mar 2020.
- MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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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.
Amin M Alousi principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Best Practice, Fecal Microbiota Transplantation and Nystatin in people with Graft-versus-host Disease Prevention, run by M.D. Anderson Cancer Center 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 5 inclusion and 9 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 4 Mar 2020. 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 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 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?
Development of acute gastrointestinal (GI) graft versus host disease (GVHD) (time frame: Within 100 days from time of transplant). The study lists 2 primary outcomes in all. 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 4 Mar 2020.