Purpose

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.

Condition

Eligibility

Eligible Ages
Between 2 Years and 25 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • All clinical and laboratory studies, if applicable, must be obtained within 21 days prior to start of protocol therapy (repeat if necessary); protocol therapy must begin within 6 months of study enrollment
  • 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)
  • Patient must be receiving cells from 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 more HLA mismatch (including haplo-identical)
  • Note: History of HCT or other cellular therapy (e.g. chimeric antigen receptor [CAR]-T cells, donor lymphocyte infusions) is permitted

Exclusion Criteria

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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Prevention
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Arm I (Lactobacillus plantarum, alloHCT)
Patients receive Lactobacillus plantarum strains 299 and 299v 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.
  • Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
    Undergo alloHCT
    Other names:
    • Allogeneic Hematopoietic Cell Transplantation
    • allogeneic stem cell transplantation
    • HSC
    • HSCT
  • Biological: Lactobacillus plantarum strain 299
    Given PO or via NG or G tube
    Other names:
    • DSM 6595
  • Biological: Lactobacillus plantarum strain 299v
    Given PO or via NG or G tube
    Other names:
    • DSM 9843
    • Lp 299v
Placebo Comparator
Arm II (placebo, alloHCT)
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.
  • Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
    Undergo alloHCT
    Other names:
    • Allogeneic Hematopoietic Cell Transplantation
    • allogeneic stem cell transplantation
    • HSC
    • HSCT
  • Other: Placebo
    Given PO or via NG or G tube
    Other names:
    • placebo therapy
    • PLCB
    • sham therapy

Recruiting Locations

Children's National and nearby locations

Children's National Medical Center
Washington, District of Columbia 20010
Contact:
Site Public Contact
202-884-2549

More Details

NCT ID
NCT03057054
Status
Recruiting
Sponsor
Children's Oncology Group

Detailed Description

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 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 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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.