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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Graft Versus Host Disease

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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lactobacillus rhamnosus GG<br>Patients receive Lactobacillus rhamnosus GG PO QD for 1 year. | Dietary Supplement: Lactobacillus rhamnosus GG<br>* Given PO<br>* Other names: LGG;Other: laboratory biomarker analysis was not performed because of no differences in the clinical outcomes<br>* Correlative studies<br>|
| No Intervention: No intervention<br>Patients receive no intervention. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring |  | Baseline | 
| Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring |  | 1 month | 
| Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring |  | 3 months | 
| Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring |  | 6 months | 
| Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring |  | 9 months | 
| Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring |  | 12 months |