Fecal Transplant +/- Gut Decontamination in Preventing Acute Graft Versus Host Disease in Patients Given Broad-Spectrum Antibiotics

NCT03862079 | Withdrawn Phase 2 DMC FDA Drug

• 3 other identifiers: 2017-0466NCI-2019-01045P30CA016672
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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).

Conditions

Graft-versus-host Disease Prevention

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  At 6 months post-randomization

Secondary Outcomes (9)

• Microbiome diversity

  At 2 weeks post fecal microbiota transplantation (FMT) (or engraftment for control arm)

• Overall maximum stage of lower GI tract GVHD

  Within 100 days post-transplant

• Cumulative incidence of acute GVHD grade II-IV and maximum grade

  Up to 6 months

• Incidence of adverse and serious adverse events

  Within 60 days of FMT

• Incidence of bacterial blood stream infections

  Up to 6 months

Other Outcomes (3)

• Analysis of T-cell subsets

  Up to 6 months post-enrollment

• Analysis of serum/stool butyrate levels

  Up to 6 months post-enrollment

• Assessment of gut permeability

  At time of discontinuation of antibiotics (engraftment)

Study Arms (3)

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.

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.

Procedure: Fecal Microbiota Transplantation

Arm III (standard therapy)

ACTIVE COMPARATOR

Patients receive standard of care.

Other: Best Practice

Interventions

Best Practice OTHER

Given standard of care

Also known as: standard of care, standard therapy

Arm III (standard therapy)

Fecal Microbiota Transplantation PROCEDURE

Undergo FMT

Also known as: Fecal Material Transplantation, Fecal Transplantation, FMT, Poo Transplant, Poop Transplant, Stool Transplant

Arm I (TGD + FMT); Arm II (FMT)

Nystatin DRUG

Given PO

Also known as: Mycostatin, Nystex

Arm I (TGD + FMT)

Piperacillin-Tazobactam DRUG

Given PO

Also known as: PIPER/TAZO, Piperacillin/Tazobactam, Zosyn

Arm I (TGD + FMT)

Eligibility Criteria

• Age: 16 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Interventions

Practice Guidelines as Topic; Standard of Care; Fecal Microbiota Transplantation; Nystatin; Piperacillin, Tazobactam Drug Combination

Intervention Hierarchy (Ancestors)

Guidelines as Topic; Quality Assurance, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality Indicators, Health Care; Biological Therapy; Therapeutics; Macrolides; Lactones; Organic Chemicals; Tazobactam; Penicillanic Acid; Penicillins; beta-Lactams; Lactams; Amides; Piperacillin; Ampicillin; Penicillin G; Sulfur Compounds; Sulfones; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Amin M Alousi

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2019
• First Posted: March 5, 2019
• Study Start: June 1, 2020
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: March 4, 2020

Record last verified: 2020-03

Locations

US (1)