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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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)

Conditions
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Hematopoietic and Lymphoid System Neoplasm, Leukemia, Lymphoma

Intervention / Treatment
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* Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
* Biological: Lactobacillus plantarum strain 299
* Biological: Lactobacillus plantarum strain 299v
* Other: Placebo Administration


Participation Criteria
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Eligibility Criteria
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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 Lansky (for patients =< 16 years of age) or Karnofsky (for patients > 16 years of age) performance status score of >= 70; patients who are unable to walk because of a chronic underlying condition (such as paralysis), but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing performance score 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, considering only HLA-A, HLA-B, HLA-C, and HLA-DRB1 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), history of gastrointestinal GVHD, 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 bacterial infection Patient is allergic to all third or fourth generation cephalosporins, carbapenems, and all aminoglycosides, which are used to empirically treat LBP bacteremia

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (Lactobacillus plantarum, alloHCT)<br>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. | Procedure: Allogeneic Hematopoietic Stem Cell Transplantation<br>* Undergo alloHCT<br>* Other names: Stem Cell Transplantation, Allogeneic;Biological: Lactobacillus plantarum strain 299<br>* Given PO or via NJ, NG or G tube<br>* Other names: LACTOBACILLUS PLANTARUM 299;Biological: Lactobacillus plantarum strain 299v<br>* Given PO or via NJ, NG or G tube<br>* Other names: Lp 299v;|
| Placebo Comparator: Arm II (placebo, alloHCT)<br>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. | Procedure: Allogeneic Hematopoietic Stem Cell Transplantation<br>* Undergo alloHCT<br>* Other names: Stem Cell Transplantation, Allogeneic;Other: Placebo Administration<br>* Given PO or via NJ, NG or G tube<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With Stage 1-4 Gastrointestinal (GI) Acute Graft Versus Host Disease (aGVHD) | 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. | Up to 120 days post stem cell infusion |