Lactobacillus Rhamnosus GG in Reducing Incidence of Graft-Versus-Host Disease in Patients Who Have Undergone Donor Stem Cell Transplant

Not Applicable

Completed

Conditions: Graft Versus Host Disease

Interventions: Dietary Supplement: Lactobacillus rhamnosus GG
Other: laboratory biomarker analysis was not performed because of no differences in the clinical outcomes

Registration Number: NCT02144701

Lead Sponsor: Rutgers, The State University of New Jersey

Brief Summary: This randomized pilot clinical trial studies Lactobacillus rhamnosus GG in reducing incidence of graft-versus-host disease in patients who have undergone donor stem cell transplant. Lactobacillus rhamnosus GG may be effective at preventing for graft-versus-host disease caused by a donor stem cell transplant.

Detailed Description: PRIMARY OBJECTIVES:

I. To determine if hematopoietic stem cell transplant (HSCT) patients treated with a probiotic (Lactobacillus GG \[Lactobacillus rhamnosus GG\])-containing diet compared to those not assigned to receive probiotic have a lower incidence of grade 1 upper gastrointestinal (GI) or grade 2-4 lower GI acute graft-versus-host disease (GVHD) (aGVHD) using Center for International Blood and Marrow Transplant Research (CIBMTR) scoring than those not prescribed a probiotic.

II. To determine if HSCT patients treated with a probiotic-containing diet compared to those not assigned to receive a probiotic have a: a) lower rate of organ-specific acute aGVHD (intestinal tract, skin, liver); b) lower rate of moderate or severe chronic GVHD (National Institutes of Health \[NIH\] consensus scoring) at 6 months and 1 year post transplant; c) shorter duration of immunosuppressive therapy (normalized for age and degree of human leukocyte antigen \[HLA\] match); d) lower rate of bacterial and/or opportunistic infection.

SECONDARY OBJECTIVES:

I. To determine if allogeneic hematopoietic stem cell patients treated with a probiotic compared to those not assigned to receive a probiotic have differences in: a) composition and proportion of the major gut bacterial phylotypes in stool (to be analyzed for changes pre- and post-initiation of probiotics and for association with development of aGVHD); b) measures of inflammation as assessed by cytokine or receptor production (interleukin \[IL\]-6, IL-8, tumor necrosis factor \[TNF\]-alpha, TNF-receptor 1, interferon-gamma, IL-2R, IL-10); c) qualitative measures of immune reconstitution as determined by sequential measurements of conventional T cells, regulatory T regulatory, B cells and natural killer (NK) cells; d) antibody class/subclass production; e) biomarkers associated with GVHD-elafin, regenerating islet-derived 3 alpha (Reg3a), suppressor of tumorigenicity-2 (ST2), hepatocyte growth factor (HGF); and/or urinary tryptophan metabolites; f) markers of gut barrier function including blood levels of endotoxin and microbial deoxyribonucleic acid (DNA).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive Lactobacillus rhamnosus GG orally (PO) once daily (QD) for 1 year.

ARM II: Patients receive no intervention.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 33

Inclusion Criteria

Able to sign informed consent
Undergoing allogeneic HSCT from a related or unrelated donor
Hematopoietic engraftment as evidenced by recovery of the absolute neutrophil count to greater than 500/mm^3 for > 3 days without filgrastim (G-CSF) support and within 40 days of transplant (i.e. complete blood counts [CBCs] obtained 3 or more days apart while off of G-CSF must demonstrate an absolute neutrophil count > 500/mm^3); if absolute neutropenia is not achieved due to a non-myeloablative transplant, the patient can be enrolled on day +21 to +40
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

Exclusion Criteria

Evidence of GVHD at the time of enrollment as assessed clinically
Serum creatinine greater than 3.0
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 3 times the upper limit of normal
Total bilirubin greater than 2 times upper limit of normal
Prior use of probiotics within 3 months prior to enrollment
Inability to take medications by mouth
Prior history of inflammatory bowel disease or other chronic diarrheal illness
Prior history of hypersensitivity to milk proteins
Active Clostridium difficile infection or on prophylactic or tapering antibiotics for Clostridium difficile infection

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lactobacillus rhamnosus GG	laboratory biomarker analysis was not performed because of no differences in the clinical outcomes	Patients receive Lactobacillus rhamnosus GG PO QD for 1 year.
Lactobacillus rhamnosus GG	Lactobacillus rhamnosus GG	Patients receive Lactobacillus rhamnosus GG PO QD for 1 year.

Primary Outcome Measures