Microbial Colonization
Conditions
Keywords
Rifaximin, Microbiome, Allogeneic hematopoietic stem cell transplantation, Blood stream infections, Acute graft versus host disease
Brief summary
Primary purpose of the study is to see if rifaximin can improve the balance of bacteria within the gut, which has been shown to improve transplant outcomes. It will also assess whether rifaximin can reduce the risk of infection in blood/marrow transplant (BMT).
Detailed description
This study is for patients who will be having a blood/marrow transplant (BMT) to treat leukemia, lymphoma or other cancer of the blood. The blood or marrow cells will come from another person (donor)-allogeneic BMT. Bacterial infections and acute graft versus host disease (AGVHD) are frequent complications of allogeneic BMT. Bacterial infections sometimes happen because injury to the gut during transplant allows gut bacteria to cross the injured gut barrier and get to the blood. AGVHD happens when certain white blood cells, called T-cells, in the donor cells (the graft) attack the patient's body. Primary purpose of the study is to see if rifaximin can improve the balance of bacteria within the gut, which has been shown to improve transplant outcomes. It will also assess whether rifaximin can reduce the risk of infection in blood/marrow transplant (BMT).
Interventions
DRUGRifaximin
Rifaximin will be administered twice a day orally or by nasogastric tube, at a dose of 15 mg/kg divided BID with a maximum dose of 1,650 mg, day -7 to day +28 or discharge (maximum duration 36 days).
Sponsors
Emory University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Pilot, single arm prospective study with retrospective control arm
Eligibility
Sex/Gender
ALL
Age
2 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
1. Allogeneic HSCT recipients between the ages of 2 and 21 years. 2. Underlying hematologic malignancy, regardless of donor type or graft source. 3. Myeloablative conditioning regimen.
Exclusion criteria
1. Known hypersensitivity to rifaximin, or other rifamycin antimicrobial agents. 2. Minimally toxic conditioning regimen (e.g. low dose TBI based). Since these regimens induce minimal myelosuppression and gut injury, patients receiving them probably stand little to gain from antibiotic prophylaxis. 3. Patients with ongoing bacterial, viral or fungal active infections are not eligible for this study. Patients who remain on broad spectrum antibiotics for the treatment of a previous infection are not eligible. 4. The use of prophylactic antibiotics is not permitted. 5. Following the standard practice in blood and marrow transplantation, pregnant or breast feeding patients will be excluded
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Alterations to microbiome diversity in children treated with rifaximin compared to the historical cohort. | Period between the start of the preparative regimen and day 28 post transplant | Composition will be assessed using 16S RNA sequencing. The Shannon index will be calculated for quantification of bacterial diversity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rates of BSI pathogen infection/colonization frequency during the treatment period compared to the historical cohort. | Period between the start of the preparative regimen and day 28 post transplant | Results of the GI pathogen panel, a test incorporated into routine patient care detecting DNA or RNA of 22 common viral, bacterial, and parasitic organisms, will provide a second assessment through molecular detection of the presence of common organisms associated with intestinal dysbiosis. |
| Transplant related mortality (TRM) | Period between the start of the preparative regimen and day 28 post transplant | Number of deaths occurring in continuous complete remission. |
| Number of patients with Chronic GVHD including overlap syndrome | Period between the start of the preparative regimen and year 5 post-transplant. | Chronic GVHD including overlap syndrome, will be assessed according to the 2014 NIH consensus criteria. |
| Number of patients with Acute GVHD | Period between the start of the preparative regimen and day 100 post transplant | Early onset (before day 100) acute GVHD (including all grades, and stratified by grades) will be assessed according to the Blood and Marrow Transplant Clinical Trials Network Manual version 2, 2005, section 1 using the NIH consensus criteria |
| Number of patients with relapse free survival at 1 year | Period between the start of the preparative regimen and year 1 post-transplant. | Survival without relapse of underlying malignancy. |
| Overall number of patients survived at 1 year | Period between the start of the preparative regimen and year 1 post-transplant. | Survival with or without relapse of underlying malignancy. |
| Number of patients with other Infections | Period between the start of the preparative regimen and day 28 post transplant | Other Infections will be defined in accordance with the Blood and Marrow Transplant Clinical Trials Network Manual of Procedures |
Countries
United States
Outcome results
None listed