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.

Study Overview

• Status: Completed
• Conditions: Graft Versus Host Disease
• Intervention / Treatment: Dietary supplement: Lactobacillus rhamnosus GG; Other: laboratory biomarker analysis was not performed because of no differences in the clinical outcomes

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.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lactobacillus rhamnosus GG; Patients receive Lactobacillus rhamnosus GG PO QD for 1 year.	Dietary supplement: Lactobacillus rhamnosus GG; Given PO; Other Names: Culturelle; LGG; Gefilus; Other: laboratory biomarker analysis was not performed because of no differences in the clinical outcomes; Correlative studies
No Intervention: No intervention; Patients receive no intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey
• Collaborators: National Cancer Institute (NCI); Rutgers Cancer Institute of New Jersey

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2013
• Primary Completion (Actual): February 28, 2016
• Study Completion (Actual): February 28, 2018

Study Registration Dates

• First Submitted: May 20, 2014
• First Submitted That Met QC Criteria: May 20, 2014
• First Posted (Estimate): May 22, 2014

Study Record Updates

• Last Update Posted (Actual): April 27, 2021
• Last Update Submitted That Met QC Criteria: April 23, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease
• Other Study ID Numbers: Pro2012001625 (Other Identifier: IRB number); P30CA072720 (U.S. NIH Grant/Contract); NCI-2013-00094 (Registry Identifier: CTRP (Clinical Trial Reporting Program))