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

PRIMARY OBJECTIVES:

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 initial alternative donor allogeneic hematopoietic cell
transplantation (alloHCT).

SECONDARY 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?, TNF?, 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 100 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
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 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.

Inclusion Criteria:

- Patient must have a diagnosis that is managed with an alternative donor allogeneic
hematopoietic cell transplant

- Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0 or 1 (>= 70% for Karnofsky/Lansky); use Karnofsky for
patients > 16 years of age and Lansky for patients =< 16 years of age

- Hematopoietic cell transplant (HCT)

- No previous history of HCT or other cellular therapy (e.g., chimeric antigen
receptor [CAR]-T cells, donor lymphocyte infusions)

- Patient must be receiving cells from a first alternative donor defined as one of
the following:

- Unrelated donor with a complete human leukocyte antigen (HLA) match or a 1
or 2 HLA mismatch

- Related donor with a 1 or 2 HLA mismatch

Exclusion Criteria:

- Patient plans on receiving stem cells from a matched (8/8) related donor

- Patient plans on receiving stem cells from a donor who has a 3 or more HLA mismatch

- Patient has used a probiotic dietary supplement within the previous 30 days of
enrollment; (consumption of yogurt products is allowed)

- Patient has a history of severe GI tract insult including but not limited to previous
bowel perforation, grade 4 neutropenic colitis or typhlitis, inflammatory bowel
syndrome, short small bowel syndrome (Crohn?s disease, ulcerative colitis) or history
of bowel resection

- Patient has a medical, psychiatric or social issue that would compromise patient
safety or compliance with protocol therapy, or interfere with consent, study
participation, follow up, or interpretation of study results

- Female patients who are pregnant are not eligible; women of childbearing potential
require a negative pregnancy test prior to enrollment

- Patient has diarrhea at the time of enrollment which is Clostridium difficile toxin
positive

- Patient is receiving antibiotic therapy for an active infection

- Patient is allergic to the third or fourth generation celphalosporins, carbapenem, or
aminoglycosides which are used to empirically treat LBP bacteremia