Clinical trial NCT03862079: Fecal Transplant +/- Gut Decontamination in Preventing Acute Graft Versus Host Disease in Patients Given Broad-Spectrum Antibiotics
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Graft-versus-host Disease Prevention
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2019-03-05
Enrollment: 0
Sex: ALL
Minimum age (years): 16
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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. 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:

I. 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:

I. 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* 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

Primary outcomes:
measure: Development of acute gastrointestinal (GI) graft versus host disease (GVHD)
timeFrame: Within 100 days from time of transplant
measure: Relapse-free survival
timeFrame: At 6 months post-randomization
Secondary outcomes:
measure: Microbiome diversity
timeFrame: At 2 weeks post fecal microbiota transplantation (FMT) (or engraftment for control arm)
measure: Overall maximum stage of lower GI tract GVHD
timeFrame: Within 100 days post-transplant
measure: Cumulative incidence of acute GVHD grade II-IV and maximum grade
timeFrame: Up to 6 months
measure: Incidence of adverse and serious adverse events
timeFrame: Within 60 days of FMT
measure: Incidence of bacterial blood stream infections
timeFrame: Up to 6 months
measure: Hematologic recovery (neutrophils and platelets)
timeFrame: Up to 6 months
measure: Characterization of the intestinal microbiota
timeFrame: Baseline up to 6 months
measure: Non-relapse mortality
timeFrame: At 6 months post-randomization
measure: Overall survival
timeFrame: At 6 months post-randomization
Other outcomes:
measure: Analysis of T-cell subsets
timeFrame: Up to 6 months post-enrollment
measure: Analysis of serum/stool butyrate levels
timeFrame: Up to 6 months post-enrollment
measure: Assessment of gut permeability
timeFrame: At time of discontinuation of antibiotics (engraftment)
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Amin M Alousi
role: PRINCIPAL_INVESTIGATOR
References: