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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2019-01045 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| 2017-0466 | Other Identifier | M D Anderson Cancer Center | |
| P30CA016672 | U.S. NIH Grant/Contract | View source |
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Per PI's request
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| Arm III (standard therapy) | Active Comparator | Patients receive standard of care. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Best Practice | Other | Given standard of care |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | At 2 weeks post fecal microbiota transplantation (FMT) (or engraftment for control arm) |
| Measure | Description | Time Frame |
|---|---|---|
| Analysis of T-cell subsets | Analysis of T-cell subsets (including specifically regulatory T-cells) will be performed by characterization of peripheral blood flow cytometry. | Up to 6 months post-enrollment |
| Analysis of serum/stool butyrate levels |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Amin M Alousi | M.D. Anderson Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| M D Anderson Cancer Center | Houston | Texas | 77030 | United States |
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| Label | URL |
|---|---|
| MD Anderson Cancer Center Website | View source |
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| Fecal Microbiota Transplantation | Procedure | Undergo FMT |
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| Nystatin | Drug | Given PO |
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| Piperacillin-Tazobactam | Drug | Given PO |
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| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | At 6 months post-randomization |
| Up to 6 months post-enrollment |
| Assessment of gut permeability | Will be performed via lactulose/ mannitol assay. | At time of discontinuation of antibiotics (engraftment) |
| ID | Term |
|---|---|
| D017410 | Practice Guidelines as Topic |
| D059039 | Standard of Care |
| D000069467 | Fecal Microbiota Transplantation |
| D009761 | Nystatin |
| D000077725 | Piperacillin, Tazobactam Drug Combination |
| ID | Term |
|---|---|
| D017408 | Guidelines as Topic |
| D011785 | Quality Assurance, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |
| D019984 | Quality Indicators, Health Care |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D000078142 | Tazobactam |
| D010397 | Penicillanic Acid |
| D010406 | Penicillins |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 | Amides |
| D010878 | Piperacillin |
| D000667 | Ampicillin |
| D010400 | Penicillin G |
| D013457 | Sulfur Compounds |
| D013450 | Sulfones |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
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