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

• Sponsor: Rutgers, The State University of New Jersey (Other)
• Overall Status: Completed
• CT.gov ID: NCT02144701
• Collaborator: Rutgers Cancer Institute of New Jersey (Other), National Cancer Institute (NCI) (NIH)
• Enrollment: 33
• Location: 1
• Arms: 2
• Actual Duration (Months): 60.3
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Graft Versus Host Disease	Dietary Supplement: Lactobacillus rhamnosus GG; Other: laboratory biomarker analysis was not performed because of no differences in the clinical outcomes	N/A

Detailed Description

PRIMARY OBJECTIVES:

1. 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.

2. 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:

1. 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 Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: A Randomized Trial Testing a Probiotic Enteric Regimen for Easing Complications of Transplant (Randomized PERFECT Trial)
• Actual Study Start Date: Feb 18, 2013
• Actual Primary Completion Date: Feb 28, 2016
• Actual Study Completion Date: Feb 28, 2018

Arms and Interventions

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 Gefilus LGG ; 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.

Outcome Measures

Primary Outcome Measures

1. Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring [Baseline]

2. Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring [1 month]

3. Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring [3 months]

4. Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring [6 months]

5. Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring [9 months]

6. Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring [12 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903

Sponsors and Collaborators

• Rutgers, The State University of New Jersey
• Rutgers Cancer Institute of New Jersey
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Roger Strair, Rutgers Cancer Institute of New Jersey

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Roger Strair, MD, PhD, Professor of Medicine, RWJMS, Rutgers Cancer Institute of New Jersey
• ClinicalTrials.gov Identifier: NCT02144701
• Other Study ID Numbers: Pro2012001625; NCI-2013-00094; Pro2012001625; P30CA072720
• First Posted: May 22, 2014
• Last Update Posted: Apr 27, 2021
• Last Verified: Apr 1, 2021

• Additional relevant MeSH terms: Graft vs Host Disease

Study Results

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 Detail	We are reporting results on 33 eligible patients. 18 patients were deemed ineligible.

Arm/Group Title	Lactobacillus Rhamnosus GG	no Intervention
Arm/Group Description	Patients receive Lactobacillus rhamnosus GG PO QD for 1 year. Lactobacillus rhamnosus GG: Given PO laboratory biomarker analysis: Correlative studies	Patients receive no intervention.
Period Title: Overall Study
STARTED	22	11
COMPLETED	13	8
NOT COMPLETED	9	3

Baseline Characteristics

Arm/Group Title	Arm I (Lactobacillus Rhamnosus GG)	Arm II (no Intervention)	Total
Arm/Group Description	Patients receive Lactobacillus rhamnosus GG PO QD for 1 year. Lactobacillus rhamnosus GG: Given PO laboratory biomarker analysis: Correlative studies	Patients receive no intervention.	Total of all reporting groups
Overall Participants	21	10	31
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	19 90.5%	7 70%	26 83.9%
>=65 years	2 9.5%	3 30%	5 16.1%
Sex: Female, Male (Count of Participants)
Female	12 57.1%	3 30%	15 48.4%
Male	9 42.9%	7 70%	16 51.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 14.3%	2 20%	5 16.1%
Not Hispanic or Latino	18 85.7%	8 80%	26 83.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 14.3%	1 10%	4 12.9%
White	16 76.2%	8 80%	24 77.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 9.5%	1 10%	3 9.7%
Region of Enrollment (participants) [Number]
United States	21 100%	10 100%	31 100%

Outcome Measures

1. Primary Outcome

Title	Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Lactobacillus Rhamnosus GG)	Arm II (no Intervention)
Arm/Group Description	Patients receive Lactobacillus rhamnosus GG PO QD for 1 year. Lactobacillus rhamnosus GG: Given PO laboratory biomarker analysis: Correlative studies	Patients receive no intervention.
Measure Participants	20	11
Count of Participants [Participants]	10 47.6%	4 40%

2. Primary Outcome

Title	Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring
Time Frame	1 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Lactobacillus Rhamnosus GG)	Arm II (no Intervention)
Arm/Group Description	Patients receive Lactobacillus rhamnosus GG PO QD for 1 year. Lactobacillus rhamnosus GG: Given PO laboratory biomarker analysis: Correlative studies	Patients receive no intervention.
Measure Participants	10	4
Count of Participants [Participants]	10 47.6%	4 40%

3. Primary Outcome

Title	Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Lactobacillus Rhamnosus GG)	Arm II (no Intervention)
Arm/Group Description	Patients receive Lactobacillus rhamnosus GG PO QD for 1 year. Lactobacillus rhamnosus GG: Given PO laboratory biomarker analysis: Correlative studies	Patients receive no intervention.
Measure Participants	10	4
Count of Participants [Participants]	10 47.6%	4 40%

4. Primary Outcome

Title	Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Lactobacillus Rhamnosus GG)	Arm II (no Intervention)
Arm/Group Description	Patients receive Lactobacillus rhamnosus GG PO QD for 1 year. Lactobacillus rhamnosus GG: Given PO laboratory biomarker analysis: Correlative studies	Patients receive no intervention.
Measure Participants	10	4
Count of Participants [Participants]	10 47.6%	4 40%

5. Primary Outcome

Title	Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring
Time Frame	9 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Lactobacillus Rhamnosus GG)	Arm II (no Intervention)
Arm/Group Description	Patients receive Lactobacillus rhamnosus GG PO QD for 1 year. Lactobacillus rhamnosus GG: Given PO laboratory biomarker analysis: Correlative studies	Patients receive no intervention.
Measure Participants	10	4
Count of Participants [Participants]	10 47.6%	4 40%

6. Primary Outcome

Title	Rate of Grade 1 Upper GI and/or 2-4 Lower GI aGVHD Assessed Using CIBMTR Scoring
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Lactobacillus Rhamnosus GG)	Arm II (no Intervention)
Arm/Group Description	Patients receive Lactobacillus rhamnosus GG PO QD for 1 year. Lactobacillus rhamnosus GG: Given PO laboratory biomarker analysis: Correlative studies	Patients receive no intervention.
Measure Participants	10	4
Count of Participants [Participants]	10 47.6%	4 40%

Adverse Events

Time Frame	Adverse events were collected over a period of one year.
Arm/Group Title	Arm I (Lactobacillus Rhamnosus GG)		Arm II (no Intervention)
Arm/Group Description	Patients receive Lactobacillus rhamnosus GG PO QD for 1 year. Lactobacillus rhamnosus GG: Given PO laboratory biomarker analysis: Correlative studies		Patients receive no intervention.
All Cause Mortality
	Arm I (Lactobacillus Rhamnosus GG)		Arm II (no Intervention)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/21 (19%)		1/10 (10%)
Serious Adverse Events
	Arm I (Lactobacillus Rhamnosus GG)		Arm II (no Intervention)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Arm I (Lactobacillus Rhamnosus GG)		Arm II (no Intervention)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.