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Broad-Spectrum Antibiotics in Treating Fever and Neutropenia in Patients Undergoing Stem Cell Transplant

Trial Status: Active

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, and aztreonam, 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 and aztreonam will have less of an effect on friendly gut bacteria.

Inclusion Criteria

  • Patients with any hematologic malignancy undergoing either an unmodified allogeneic HCT or a double umbilical cord blood transplant with or without the infusion of T-cell depleted HLA-haploidentical peripheral blood stem cells
  • Patients undergoing an unmodified transplant must have a related or unrelated marrow or peripheral blood stem cell (PBSC) donor as follows: * Sibling donor must be a 6/6 match for HLA-A and -B at intermediate (or higher) resolution, and HLA-DRB1 at high resolution using deoxyribonucleic acid (DNA)-based typing * Unrelated donor must be an 8/8 match at HLA-A, -B, -C and –DRB1 at high resolution using DNA-based typing

Exclusion Criteria

  • Patients with severe allergies to piperacillin-tazobactam, cefepime, aztreonam or vancomycin; severe reactions include anaphylaxis and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN)
  • Patients with unconfirmed allergies to piperacillin-tazobactam, cefepime, aztreonam or vancomycin can be evaluated by an allergy/immunology specialist, after which they may become eligible by a consensus of the treating physician, trial investigator and the allergy/immunology specialist
  • Prolonged antibiotic treatment (>= 10 days, within 3 weeks of enrollment) as prevention or suppression of an ongoing infection, where treatment involves gut-perturbing anti anaerobic antibiotics
  • Patients known to be colonized with multi-drug resistant organisms or with history of infection with multi-drug resistant organisms; patients with history of infection with extended-spectrum beta-lactamase producing organism
  • Febrile patients
  • Patients with estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m^2
  • Patients receiving post-transplant cyclophosphamide as GVHD prophylaxis

New York

New York
Memorial Sloan Kettering Cancer Center
Status: ACTIVE
Contact: Boglarka Gyurkocza
Phone: 212-639-2860

PRIMARY OBJECTIVES:

I. To assess the association between antibiotic treatment strategies and the change in the relative abundance of Clostridiales.

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.

VIII. All grades >= 3 toxicities according to Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be compared across each intervention arm on post-transplant day +100.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo previously planned allogeneic hematopoietic cell transplantation. If febrile neutropenia 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 will be considered non-evaluable and will be removed from the study.

ARM II: Patients undergo previously planned allogeneic hematopoietic cell transplantation. If febrile neutropenia occurs, patients receive cefepime IV q 8 hours. Patients whose fever resolves may then be switched over to instead receive aztreonam IV q 8 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 will be considered non-evaluable and will be removed from the study.

After completion of study treatment, patients are followed up for 2 years.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Boglarka Gyurkocza

  • Primary ID 17-097
  • Secondary IDs NCI-2017-00545
  • Clinicaltrials.gov ID NCT03078010