This randomized phase II trial studies the effects of broad-spectrum antibiotics on friendly gut bacteria in patients with fever and neutropenia undergoing stem cell transplant. Broad-spectrum antibiotics, such as piperacillin-tazobactam, cefepime, aztreonam, vancomycin, are given to prevent or control fever and neutropenia. However, they may also kill off friendly gut bacteria. It is not yet known if treatment with piperacillin-tazobactam or cefepime, aztreonam, and vancomycin will have less of an effect on friendly gut bacteria.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03078010.
PRIMARY OBJECTIVE:
I. To compare microbiome diversity as reflected by fold-change in Clostridiales abundance between patients who receive initial empiric antibiotic therapy with piperacillin-tazobactam vs. cefepime for any episode of febrile neutropenia arising between initiation of conditioning and neutrophil engraftment.
SECONDARY OBJECTIVES:
I. Compare incidence of acute and chronic graft versus host disease (GVHD) and GVHD-related mortality after allogeneic hematopoietic cell transplant (HCT).
II. Compare overall survival (OS), non-relapse mortality (NRM) and relapse after allogeneic HCT.
III. Compare the rates of bloodstream infections on post-transplant day +100.
IV. Compare the rate of defervescence, time to defervescence in patients with febrile neutropenia between initiation of conditioning and engraftment.
V. Compare the proportion of patients who require antibiotic escalation/adjustment between the two study arms.
VI. Assess differences in intestinal bacterial flora diversity and Blautia abundance between treatment arms.
VII. Identify microbiota markers associated with increased or decreased risk for acute GVHD.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients undergo previously planned allogeneic hematopoietic cell transplantation. If febrile neutropenia or afebrile neutropenia with signs or symptoms suggestive of infection occurs, patients receive piperacillin-tazobactam intravenously (IV) every (q) 6 hours. Antibiotic therapy is continued per clinical practice guidelines. Patients provide fecal specimens 3 times a week (Monday, Wednesday, and Friday) from the day of initiating conditioning or enrollment (whichever occurs later) until completion of antibiotic therapy and on post-transplant days 28, 56, and 100. Patients who do not develop febrile neutropenia before neutrophil engraftment are considered non-evaluable and are removed from the study.
ARM II: Patients undergo previously planned allogeneic hematopoietic cell transplantation. If febrile neutropenia or afebrile neutropenia with signs or symptoms suggestive of infection occurs, patients receive cefepime IV q 8 hours. Patients whose fever resolves for >= 72 hours, may then be switched over to instead receive aztreonam IV q 8 hours and vancomycin IV q 12 hours, or prior quinolone prophylaxis (levofloxacin orally [PO] or IV daily or ciprofloxacin IV or PO q 12 hours) per treating physician’s discretion, within 4-5 days of initiation of cefepime, to further preserve intestinal microbiome integrity. Antibiotic therapy is continued per clinical practice guidelines. Patients provide fecal specimens 3 times a week (Monday, Wednesday, and Friday) from the day of initiating conditioning or enrollment (whichever occurs later) until completion of antibiotic therapy and on post-transplant days 28, 56, and 100. Patients who do not develop febrile neutropenia before neutrophil engraftment are considered non-evaluable and are removed from the study.
After completion of study treatment, patients are followed up for 2 years.
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorSusan K. Seo
