Clinical trial NCT02144701: Lactobacillus Rhamnosus GG in Reducing Incidence of Graft-Versus-Host Disease in Patients Who Have Undergone Donor Stem Cell Transplant
Official title: A Randomized Trial Testing a Probiotic Enteric Regimen for Easing Complications of Transplant (Randomized PERFECT Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Graft Versus Host Disease
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
Collaborators: name: Rutgers Cancer Institute of New Jersey
name: National Cancer Institute (NCI)
First posted: 2014-05-22
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring
timeFrame: Baseline
measure: Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring
timeFrame: 1 month
measure: Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring
timeFrame: 3 months
measure: Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring
timeFrame: 6 months
measure: Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring
timeFrame: 9 months
measure: Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
Study officials:
affiliation: Rutgers Cancer Institute of New Jersey
name: Roger Strair
role: PRINCIPAL_INVESTIGATOR
References: