Antibiotics for Protecting Gut Bacteria During Stem Cell Transplant

Recruiting at 1 trial location

Overseen By Jonathan Peled, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 29

Duration: 7 days

347 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to see how different antibiotics affect the community of friendly bacteria existing in the intestinal tract (gut). Under normal circumstances, these friendly bacteria are not harmful and they help with normal bodily functions such as digestion. When these bacteria are absent, several complications may occur, such as infections with harmful bacteria or other inflammatory reactions, that can complicate the stem cell transplant course. Treatment with antibiotics or chemotherapy is known to kill off these friendly bacteria. In this study we compare the effects of different antibiotics on the community of friendly bacteria in the gut. For microbiota-related biomarker analysis, optional urine samples (MSKCC patients only) will be collected at baseline, 7 +/-2 days after initiation of antibiotic therapy, and on post-transplant days +28, +56 and +100 (+/- 7days).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on prolonged antibiotic treatment for an ongoing infection, you may not be eligible to participate.

What data supports the effectiveness of the drug Cefepime, Piperacillin-tazobactam, Zosyn, Tazocin for protecting gut bacteria during stem cell transplant?

Research indicates that while piperacillin-tazobactam is associated with increased risks of graft-versus-host disease (GVHD) and mortality, cefepime does not show this association, suggesting cefepime might be a safer option for protecting gut bacteria during stem cell transplants. ^{1 2 3 4 5}

Is the use of antibiotics like Cefepime and Piperacillin-tazobactam safe for protecting gut bacteria during stem cell transplants?

Cefepime is generally not associated with increased mortality related to graft-versus-host disease (GVHD) after stem cell transplants, while Piperacillin-tazobactam may increase GVHD-related mortality and cause changes in gut bacteria. Piperacillin-tazobactam has also been linked to bone marrow suppression and a higher risk of kidney injury when used with vancomycin, but it is generally considered safe for treating febrile neutropenia in some studies. ^{1 4 6 7 8}

How does the drug used in the trial protect gut bacteria during stem cell transplants?

The trial explores using antibiotics to protect gut bacteria during stem cell transplants, which is unique because it focuses on minimizing harm to beneficial gut bacteria, unlike some broad-spectrum antibiotics that can increase the risk of complications like graft-versus-host disease (GVHD). This approach aims to balance treating infections while preserving the gut's microbial balance, which is crucial for patient outcomes. ^{1 4 6 9 10}

Research Team

Susan Seo, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults with blood cancers undergoing stem cell transplants can join this trial. They must not have been on gut-affecting antibiotics for long periods recently, should not currently have a fever, and their kidneys need to work well. Those allergic to the study drugs or with certain drug-resistant infections cannot participate.

Inclusion Criteria

I am undergoing treatment for a blood cancer.

Exclusion Criteria

I currently have a fever.

My kidney function is low, with an eGFR under 30.

I have been on strong antibiotics for more than 10 days recently to prevent or treat an infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either piperacillin-tazobactam or cefepime to assess the impact on gut bacteria

7 days

Baseline visit, 1 visit (in-person) at 7 days

Follow-up

Participants are monitored for changes in gut microbiota and safety post-treatment

14 weeks

Visits on post-transplant days +28, +56, and +100

Treatment Details

Interventions

• Cefepime
• Piperacillin-tazobactam

Trial Overview The trial is testing how two antibiotics, Piperacillin-tazobactam and cefepime, impact the good bacteria in the gut during stem cell transplant recovery. It will involve monitoring changes in these bacteria through urine samples at several points before and after starting antibiotic therapy.

Participant Groups

Group I: cefepime Experimental Treatment 1 Intervention

Group II: Piperacillin-tazobactam Active Control 1 Intervention

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

References

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

Increased GVHD-related mortality with broad-spectrum antibiotic use after allogeneic hematopoietic stem cell transplantation in human patients and mice. [2023]

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

Anaerobic Antibiotics and the Risk of Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation. [2021]

3. France pubmed.ncbi.nlm.nih.gov

[Prevention of bacterial infections after bone marrow graft by broad-spectrum oral antibiotics, absorbable (pefloxacin, penicillin) and non absorbable (cephalosporin, gentamycin, bacitracin)]. [2006]

4. England pubmed.ncbi.nlm.nih.gov

Impact of choice, timing, sequence and combination of broad-spectrum antibiotics on the outcome of allogeneic haematopoietic stem cell transplantation. [2019]

5. France pubmed.ncbi.nlm.nih.gov

[Randomized trial of empirical antibiotic therapy in febrile episodes after bone marrow transplantation. Comparison of an aminoglycoside-beta lactam (tobramycin-ticarcillin) combination with 2 beta-lactam antibiotics (ticarcillin-latamoxef)]. [2013]

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

Piperacillin induced bone marrow suppression: a case report. [2018]

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

Acute Kidney Injury in Hematopoietic Cell Transplantation Patients Receiving Vancomycin and Piperacillin/Tazobactam Versus Vancomycin and Cefepime. [2019]

8. Japan pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of piperacillin-tazobactam for febrile neutropenic patients in Japan]. [2018]

9. Denmark pubmed.ncbi.nlm.nih.gov

[Piperacillin/tazobactam--Tazocin. A penicillin-based alternative to 3rd generation cephalosporins and carbapenems]. [2013]

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

Review of piperacillin/tazobactam in the treatment of bacteremic infections and summary of clinical efficacy. [2019]