Graft Versus Host Disease
Conditions
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.
Interventions
DIETARY_SUPPLEMENTLactobacillus rhamnosus GG
Given PO
OTHERlaboratory biomarker analysis was not performed because of no differences in the clinical outcomes
Correlative studies
Sponsors
Rutgers Cancer Institute of New Jersey
National Cancer Institute (NCI)
Rutgers, The State University of New Jersey
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring | Baseline |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited through the Rutgers Cancer Institute of New Jersey. The study was open to accrual on 02/18/2013 and was closed to accrual on 04/22/2016.
Pre-assignment details
We are reporting results on 33 eligible patients. 18 patients were deemed ineligible.
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Lactobacillus Rhamnosus GG) Patients receive Lactobacillus rhamnosus GG PO QD for 1 year.
Lactobacillus rhamnosus GG: Given PO
laboratory biomarker analysis: Correlative studies | 21 |
| Arm II (no Intervention) Patients receive no intervention. | 10 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | development of relapse, GVHD or death | 9 | 3 |
Baseline characteristics
| Characteristic | Arm I (Lactobacillus Rhamnosus GG) | Arm II (no Intervention) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 3 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 7 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 8 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) White | 16 Participants | 8 Participants | 24 Participants |
| Region of Enrollment United States | 21 participants | 10 participants | 31 participants |
| Sex: Female, Male Female | 12 Participants | 3 Participants | 15 Participants |
| Sex: Female, Male Male | 9 Participants | 7 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 21 | 1 / 10 |
| other Total, other adverse events | 0 / 21 | 0 / 10 |
| serious Total, serious adverse events | 0 / 21 | 0 / 10 |
Outcome results
Primary
Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring
Time frame: Baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Lactobacillus Rhamnosus GG) | Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring | 10 Participants |
| Arm II (no Intervention) | Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring | 4 Participants |
Primary
Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring
Time frame: 1 month
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Lactobacillus Rhamnosus GG) | Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring | 10 Participants |
| Arm II (no Intervention) | Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring | 4 Participants |
Primary
Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring
Time frame: 3 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Lactobacillus Rhamnosus GG) | Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring | 10 Participants |
| Arm II (no Intervention) | Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring | 4 Participants |
Primary
Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Lactobacillus Rhamnosus GG) | Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring | 10 Participants |
| Arm II (no Intervention) | Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring | 4 Participants |
Primary
Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring
Time frame: 9 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Lactobacillus Rhamnosus GG) | Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring | 10 Participants |
| Arm II (no Intervention) | Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring | 4 Participants |
Primary
Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Lactobacillus Rhamnosus GG) | Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring | 10 Participants |
| Arm II (no Intervention) | Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring | 4 Participants |