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

NCT ID: NCT03057054

Last Updated: 2025-10-06

Study Results

Results available

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

173 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-04-30

Study Completion Date

2026-06-30

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.

Conditions

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Acute Graft Versus Host Disease Hematopoietic and Lymphatic System Neoplasm Leukemia Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Arm I (Lactobacillus plantarum, alloHCT)

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.

Group Type EXPERIMENTAL

Allogeneic Hematopoietic Stem Cell Transplantation

Intervention Type PROCEDURE

Undergo alloHCT

Lactobacillus plantarum strain 299

Intervention Type BIOLOGICAL

Given PO or via NJ, NG or G tube

Lactobacillus plantarum strain 299v

Intervention Type BIOLOGICAL

Given PO or via NJ, NG or G tube

Arm II (placebo, alloHCT)

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.

Group Type PLACEBO_COMPARATOR

Allogeneic Hematopoietic Stem Cell Transplantation

Intervention Type PROCEDURE

Undergo alloHCT

Placebo Administration

Intervention Type OTHER

Given PO or via NJ, NG or G tube

Interventions

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Allogeneic Hematopoietic Stem Cell Transplantation

Undergo alloHCT

Intervention Type PROCEDURE

Lactobacillus plantarum strain 299

Given PO or via NJ, NG or G tube

Intervention Type BIOLOGICAL

Lactobacillus plantarum strain 299v

Given PO or via NJ, NG or G tube

Intervention Type BIOLOGICAL

Placebo Administration

Given PO or via NJ, NG or G tube

Intervention Type OTHER

Other Intervention Names

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Allogeneic Allogeneic Hematopoietic Cell Transplantation Allogeneic Stem Cell Transplantation HSC HSCT Stem Cell Transplantation, Allogeneic DSM 6595 LACTOBACILLUS PLANTARUM 299 DSM 9843 LACTIPLANTIBACILLUS PLANTARUM 299V Lp 299v

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
Minimum Eligible Age

2 Years

Maximum Eligible Age

25 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael L Nieder

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

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Children's Hospital of Alabama

Birmingham, Alabama, United States

Site Status

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

UCSF Benioff Children's Hospital Oakland

Oakland, California, United States

Site Status

Rady Children's Hospital - San Diego

San Diego, California, United States

Site Status

UCSF Medical Center-Mission Bay

San Francisco, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

Yale University

New Haven, Connecticut, United States

Site Status

Alfred I duPont Hospital for Children

Wilmington, Delaware, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

University of Florida Health Science Center - Gainesville

Gainesville, Florida, United States

Site Status

Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, United States

Site Status

Nemours Children's Hospital

Orlando, Florida, United States

Site Status

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, United States

Site Status

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, United States

Site Status

Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status

Children's Hospital New Orleans

New Orleans, Louisiana, United States

Site Status

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

C S Mott Children's Hospital

Ann Arbor, Michigan, United States

Site Status

Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

Grand Rapids, Michigan, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

New York Medical College

Valhalla, New York, United States

Site Status

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

The Children's Hospital at TriStar Centennial

Nashville, Tennessee, United States

Site Status

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Medical City Dallas Hospital

Dallas, Texas, United States

Site Status

Children's Hospital of San Antonio

San Antonio, Texas, United States

Site Status

Methodist Children's Hospital of South Texas

San Antonio, Texas, United States

Site Status

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, United States

Site Status

Alberta Children's Hospital

Calgary, Alberta, Canada

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, Canada

Site Status

Countries

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United States Canada

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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NCI-2017-00208

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACCL1633

Identifier Type: OTHER

Identifier Source: secondary_id

COG-ACCL1633

Identifier Type: OTHER

Identifier Source: secondary_id

ACCL1633

Identifier Type: OTHER

Identifier Source: secondary_id

R01CA201788

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UG1CA189955

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ACCL1633

Identifier Type: -

Identifier Source: org_study_id

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