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

A Randomized Trial Testing a Probiotic Enteric Regimen for Easing Complications of Transplant (Randomized PERFECT Trial)

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.

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.

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