Fecal Transplant +/- Gut Decontamination in Preventing Acute Graft Versus Host Disease in Patients Given Broad-Spectrum Antibiotics
| Status: | Not yet recruiting |
|---|---|
| Conditions: | Hematology |
| Therapuetic Areas: | Hematology |
| Healthy: | No |
| Age Range: | 16 - 75 |
| Updated: | 4/6/2019 |
| Start Date: | May 21, 2019 |
| End Date: | December 31, 2021 |
| Contact: | Amin M Alousi |
| Email: | aalousi@mdanderson.org |
| Phone: | 713-792-9556 |
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).
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).
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.
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.
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
We found this trial at
1
site
Houston, Texas 77030
Principal Investigator: Amin M. Alousi
Phone: 713-792-9556
Click here to add this to my saved trials
