Rifaximin for Preventing Acute Graft Versus Host Disease (AGVHD)

Phase 1

Completed

• Conditions: Malignancy; Bone Marrow Transplantation
• Interventions: Drug: Rifaximin

• Registration Number: NCT00967096
• Lead Sponsor: Emory University

Brief Summary

Acute graft versus host disease is a frequent and often life threatening complication of allogeneic blood and marrow transplantation. The bacteria that normally reside in the intestine play a critical role in its development. Injury to the lining of the bowel that results from the high dose chemotherapy or radiation that transplant patients receive during the week preceding the transplant allows the bacteria to invade the intestines and spread to nearby lymph nodes. This, in turn, causes inflammation which has been shown to promote GVHD. Both pre-clinical and clinical research has demonstrated that oral antibiotics can prevent graft versus host disease by inhibiting these gut bacteria. Rifaximin has several features that suggest it could be effective in preventing GVHD. Rifaximin prophylaxis might also provide an added benefit by protecting highly immunocompromised transplant patients from severe bacterial infections. This pilot trial will allow the investigators to determine the feasibility of using Rifaximin for prevention of GVHD and infection in patients undergoing allogeneic blood and marrow transplantation. The preliminary results will be used to plan a more definitive trial.

Detailed Description

Not available

Study Timeline

• Study Start: 2007-04
• Primary Completion: 2009-04
• Study Completion: 2009-04
• Study First Submitted: 2009-08-11
• Study First Submitted QC: 2009-08-26
• Study First Posted: 2009-08-27
• Status Verified: 2013-11
• Last Update Submitted: 2013-11-26
• Last Update Posted: 2013-11-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Patients must be at least 12 years old.
2. Patients will be eligible regardless of their type of disease (malignant or non-malignant), type of donor (HLA matched related, mismatched related or unrelated donors), type of hematopoietic cell source (unstimulated marrow, cytokine stimulated marrow, cytokine stimulated peripheral blood or umbilical cord blood), or GVHD prophylaxis.
3. Patients must receive a myeloablative or moderately intensive reduced intensity (at least 8 mg/kg oral busulfan (or the equivalent IV dose), or at least 100 mg/m2 of Melphalan , or at least 100 mg/kg of cyclophosphamide, or at least 500 cGy of TBI) conditioning regimen.

Exclusion Criteria

1. Age under 12 years.
2. Known hypersensitivity to rifaximin, or other rifamycin antimicrobial agents.
3. 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.
4. Patients with documented severe active infection (viral, bacterial, fungal, protozoal) will not be eligible.
5. Patients with treatment unresponsive hematologic malignant diseases (based on an assessment done within two weeks of the start of conditioning therapy).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	Rifaximin	The primary clinical endpoint to be assessed in this study will be the proportion of Rifaximin doses successfully administered. Because of mucositis, compliance with oral agents, even those that are well tolerated in other settings, may be limited in the early post-transplant period. Thus, it will be important to demonstrate the feasibility of administering Rifaximin to BMT patients before embarking on larger scale studies. Secondary outcomes will include AGVHD, event-free survival, overall survival, non-relapse mortality, neutrophil and platelet engraftment.

Primary Outcome Measures

Name	Time	Method
Determine the feasibility of this approach; to gather preliminary data on the incidence of GVHD and other clinical outcomes; to obtain pre-clinical data on the serial plasma levels of three biologic markers- endotoxin, soluble IL-2 receptor and TNF.	1 year after last patient enrolled

Secondary Outcome Measures

Name	Time	Method
Obtain preliminary data on the efficacy of administering rifaximin for prophylaxis against serious bacterial infections in BMT patients.	1 year after last patient enrolled

Trial Locations

Locations (2)

Children's Healthcare of Atlanta; 🇺🇸 Atlanta, Georgia, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States