Probiotics for Preventing Graft-versus-Host Disease

Recruiting at 46 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Children's Oncology Group

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

173 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing whether Lactobacillus plantarum, a beneficial bacteria found in foods like yogurt, can prevent a serious gut complication called acute graft versus host disease in young patients receiving stem cell transplants. The bacteria may help by keeping the gut healthy and reducing inflammation. Lactobacillus plantarum has been used in human studies to promote beneficial effects in the immune system, alleviate intestinal disorders, and reduce the risk of cardiovascular disease. The study will compare patients taking Lactobacillus plantarum to those not taking it.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on antibiotics for an active bacterial infection, you may not be eligible to participate.

What data supports the effectiveness of the treatment Lactobacillus Plantarum for preventing graft-versus-host disease?

Research suggests that probiotics like Lactobacillus can help manage graft-versus-host disease (GVHD) by altering gut bacteria and reducing inflammation. Although specific studies on Lactobacillus Plantarum are not mentioned, similar probiotics have shown potential benefits in reducing GVHD severity in experimental settings. ^{1 2 3 4 5}

Is Lactobacillus plantarum safe for use in humans?

Research indicates that Lactobacillus plantarum is safe for use in children and adolescents undergoing hematopoietic cell transplantation, with no cases of bacteremia (bacteria in the blood) or unexpected adverse events reported. ^{1 2 3 6 7}

How does the treatment Lactobacillus Plantarum differ from other treatments for preventing graft-versus-host disease?

Lactobacillus Plantarum is a probiotic treatment that aims to prevent graft-versus-host disease by altering the gut microbiome, which can help reduce inflammation and improve immune function. Unlike traditional immunosuppressive drugs, this approach focuses on maintaining a healthy balance of gut bacteria to potentially prevent the condition. ^{1 2 6 7 8}

Research Team

Michael L Nieder

Principal Investigator

Children's Oncology Group

Eligibility Criteria

This trial is for children with leukemia, lymphoma, or other blood cancers who are undergoing a donor stem cell transplant. They must have good performance status and be receiving cells from a partially matched donor. Kids can't join if they're allergic to certain antibiotics, recently took probiotics, are pregnant, have active infections or severe GI issues.

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

I can do most activities or use a wheelchair due to a condition but not because of my current illness.

I am receiving cells from a donor who is either a perfect match or has only 1-2 mismatches.

Exclusion Criteria

I plan to receive stem cells from a fully matched family member.

I have had severe gastrointestinal problems or surgeries in the past.

I am not pregnant and have a negative pregnancy test.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Transplant Conditioning

Participants receive Lactobacillus plantarum or placebo starting on day 1 of the transplant conditioning regimen

Up to 56 days

Daily administration

Allogeneic Hematopoietic Cell Transplantation (alloHCT)

Participants undergo alloHCT at day 0

1 day

Post-Transplant Treatment

Continued administration of Lactobacillus plantarum or placebo until 56 days post alloHCT

56 days

Daily administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

120 days

Regular follow-up visits

Treatment Details

Interventions

• Lactobacillus Plantarum

Trial Overview The study tests whether Lactobacillus plantarum strains (299 and 299v) can prevent acute graft versus host disease in the gut after stem cell transplants compared to a placebo. It's randomized: patients don't choose which treatment they get.

Participant Groups

Group I: Arm I (Lactobacillus plantarum, alloHCT) Experimental Treatment 3 Interventions

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 II: Arm II (placebo, alloHCT) Placebo Group 2 Interventions

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.

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

References

1. United States pubmed.ncbi.nlm.nih.gov

Probiotic effects on experimental graft-versus-host disease: let them eat yogurt. [2021]

2. Denmark pubmed.ncbi.nlm.nih.gov

Lactobacillus rhamnosus GG probiotic enteric regimen does not appreciably alter the gut microbiome or provide protection against GVHD after allogeneic hematopoietic stem cell transplantation. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Intestinal Blautia Is Associated with Reduced Death from Graft-versus-Host Disease. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Detrimental Effect of Broad-spectrum Antibiotics on Intestinal Microbiome Diversity in Patients After Allogeneic Stem Cell Transplantation: Lack of Commensal Sparing Antibiotics. [2020]

6. England pubmed.ncbi.nlm.nih.gov

The safety and feasibility of probiotics in children and adolescents undergoing hematopoietic cell transplantation. [2018]

7. England pubmed.ncbi.nlm.nih.gov

FK506 and Lactobacillus acidophilus ameliorate acute graft-versus-host disease by modulating the T helper 17/regulatory T-cell balance. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Gut microbiota intervention by pre and probiotics can induce regulatory T cells and reduce the risk of severe acute GVHD following allogeneic hematopoietic stem cell transplantation. [2023]