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Acidophilus

Patients receive Lactobacillus plantarum strains 299 and 299v PO or through NJ, NG or G tube QD on day 1 of transplant conditioning regimen to 56 days post alloHCT. Patients undergo alloHCT at day 0.

Patients receive placebo PO or through NJ, NG or G tube QD on day 1 of transplant conditioning regimen to 56 days post alloHCT. Patients undergo alloHCT at day 0.

Allogeneic Hematopoietic Stem Cell Transplantation

Lactobacillus plantarum strain 299

Lactobacillus plantarum strain 299v

Placebo Administration

Michael L Nieder

This randomized phase III trial studies how well Lactobacillus plantarum works in preventing acute graft versus host disease in children undergoing donor stem cell transplant. Lactobacillus plantarum may help prevent the development of gastrointestinal graft versus host disease in children, adolescents, and young adults undergoing donor stem cell transplant.

PRIMARY OBJECTIVE:

I. To determine efficacy of orally-administered Lactobacillus plantarum (LBP) in preventing the development of gastrointestinal (GI) acute graft versus host disease (aGvHD) in children and adolescents undergoing alternative donor allogeneic hematopoietic cell transplantation (alloHCT).

EXPLORATORY OBJECTIVES:

I. To determine whether orally-administered LBP decreases the incidence of grade II-IV aGvHD following alternative donor alloHCT.

II. To determine whether LBP administration maintains intestinal integrity as measured by mean serum citrulline levels and reduction in mucosal barrier injury (MBI) bacteremia.

III. To measure the effects of LBP on the intestinal flora phylogenetic composition during and after alternative donor alloHCT using 16S ribosomal ribonucleic acid (rRNA) gene deep sequencing.

IV. To measure effects of LBP on intestinal flora function during and after alternative donor alloHCT using metagenomic and metabolite profiling.

V. To measure proposed immunomodulatory effects of LBP in mean serum levels of alloreactive-induced inflammatory cytokines (IL-2, IL-6, IL-12p70, IFN gamma, TNF alpha, etc) in patients receiving LBP compared to placebo.

VI. To determine whether LBP administration reduces the incidence of Clostridium difficile-associated diarrhea in alternative donor HCT patients.

VII. To determine whether LBP administration reduces hospital days within the first 120 days post hematopoietic cell transplant (HCT).

VIII. To define the safety of orally administered LBP strains 299 and 299v in alternative donor HCT patients as measured by incidence of Lactobacillus plantarum bacteremia.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive Lactobacillus plantarum strains 299 and 299v orally (PO) or through nasojejunal (NJ), nasogastric (NG) or gastronomy (G) tube once daily (QD) on day 1 of transplant conditioning regimen to 56 days post alloHCT. Patients undergo alloHCT at day 0.

ARM II: Patients receive placebo PO or through NJ, NG or G tube QD on day 1 of transplant conditioning regimen to 56 days post alloHCT. Patients undergo alloHCT at day 0.

After completion of study treatment, patients are followed up for 120 days from alloHCT.

Lactobacillus Plantarum in Preventing Acute Graft Versus Host Disease in Children Undergoing Donor Stem Cell Transplant

The Effectiveness of Lactobacillus Plantarum (LBP, IND# 17339) in Preventing Acute Graft-Versus-Host Disease (GvHD) in Children Undergoing Alternative Hematopoietic Progenitor Cell Transplantation (HCT)

A similar analysis approach will be used as described for the primary outcome measure but using the dichotomous cumulative incidence of grade II-IV acute graft versus host disease as the endpoint measure.

The risk of mucosal barrier blood stream infections will be compared between two groups.

Proportion of C. diff-associated diarrhea during the study period will be compared between arms.

The change in citrulline levels from baseline to each of the time points (days 7, 14, 28, 56, and 120 post-infusion) will be summarized and described by arm.

LBP introduction on the intestinal flora via LBP administration will be compared with bacterial genes and pathways, and bacterial metabolites via correlation analyses. Also, dDescriptive analysis will be used to examine the association between the graft versus host disease outcomes (GI aGvHD and overall GvHD) and bacterial genes, pathways, and metabolites.

The association between Lactobacillus plantarum administration and bacterial genes and pathways, and bacterial metabolites will be evaluated.

The effects of Lactobacillus plantarum on pro-inflammatory (LBP) cytokines in allogeneic hematopoietic cell transplantation recipients will be examined by comparing levels across arms.

Total hospital days over the study period is calculated as the duration between the date of admission for conditional therapy and the date of discharge (or the study end date). Hospital days will be compared between arms.

Patients who have at least one incidence (positive) of lactobacillus plantarum during any reporting period is considered evaluable for this aim. The proportion of patients experiencing lactobacillus plantarum bacteremia during the study period will be compared between arms.

The proportion of eligible patients having stage 1-4 GI aGvHD occur from Day 0 through Day 120 will be compared between the two arms.

National Cancer Institute (NCI)

Children's Oncology Group

Adverse event reporting is collected routinely using case report forms. SAE field contains NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. All-Cause Mortality events were monitored/assessed in all randomized participants. Serious and Other Adverse Events were monitored/assessed only in the eligible participants.

Arm I (Lactobacillus Plantarum, alloHCT)

Arm II (Placebo, alloHCT)

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Canada

Region of Enrollment

Results Reporting Coordinator

2 patients were excluded because they were not eligible (1 patient from Group 1 and 1 patient from Group 2). 2 patients were excluded because they did not initiate treatment (1 patient from Group 1 and 1 patient from Group 2). 10 patients were excluded because they never received a stem cell infusion within 6 months of enrollment (5 patients from Group 1 and 5 patients from Group 2).

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