Early Versus Late Stopping of Antibiotics in Adults With High-risk Hematological Malignancies/Receiving Cellular Therapies and Fever

NCT07051525 | Recruiting DMC

• 3 other identifiers: 24/2362024.406ERM113654
• Study Type: interventional
• Target: 214
• Locations: 1 country
• Sites: 2

Brief Summary

Pre-neutropenic fever (PNF) (fever following chemotherapy but before developing low white cells) and neutropenic fever (NF) (fever in the setting of low white cells) are very common after chemotherapy for acute leukemia, bone marrow transplantation or Chimeric Antigen Receptor T-cell (CAR T) therapy. Often, there is no bacterial cause for fever found, and in the setting of a well patient with resolved fever, some studies have shown it to be safe to cease antibiotic therapy which was commenced at the onset of fever. This reduces the overall exposure to antibiotics, which can be beneficial to the patient (reduced risk of resistant bugs emerging, reduced serious side effects). However, some subgroups of high-risk patients have been underrepresented in these studies (in particular, those who have received a bone marrow transplant from a donor, those with longer duration of low white cells) and none have been performed in Australia, hence applying this data to our setting and patient groups is indirect and further data are needed. This study plans to recruit participants who have received chemotherapy for acute leukemia or a stem cell transplant (either their own cells or a donor's cells) or CAR T-cell therapy and perform a trial to compare early stopping of antibiotics (STOP arm) to the standard of care, which traditionally involves continuing antibiotics until the white cell count reaches above a specific threshold. The primary study outcome is duration of days free of antibiotics within 28 days of study allocation. The investigators will also observe for important clinical outcomes including rates of fever recurrence, bloodstream and other infections, intensive care admission and mortality. Patients will stay in hospital during this period, even in the setting of stopping antibiotics, and these antibiotics can be recommenced urgently according to the sepsis protocol if there is concern for infection.

Conditions

Infections, Bacterial; Leukemia; CART Therapy; Transplantation, Stem Cell

Keywords

EPIC; ELSA; Febrile neutropaenia; Febrile neutropenia; antibitoics

Outcome Measures

Primary Outcomes (1)

• Days free of antibiotic therapy in 28 days post randomization (termed empiric antibiotic free days (EAFDs))

  The primary study outcome is duration of days free of antibiotics within 28 days of study allocation. Measured as antibiotic free days in last 28 days post fever onset

  28 days after randomization

Secondary Outcomes (18)

• Days alive and free of antibiotic therapy in 28 days post randomization

  28 days after randomization

• Recurrence of fever (>38deg Celsius) beyond randomization

  same episode of neutropenia - until ANC>500 cells/mm3

• Number of occasions antibiotic therapy is recommenced with treatment intent

  Within 28 days after randomization

• Days of antibiotic therapy during neutropenic period

  Neutropenic period - until ANC>500 cells/mm3

• Number of intensive care unit (ICU) admissions

  pre-neutropenic and neutropenic period post randomization (until ANC>500 cells/mm3)

Study Arms (2)

STOP - early discontinuation of empiric antibiotic therapy

EXPERIMENTAL

Short course antibiotics (STOP): Antibiotics will be commenced at onset of fever and stopped once afebrile for 48-96 hours and clinically stable.

Drug: Early antibiotic cessation alert

SOC - standard of care continuation of empiric antibiotic therapy

NO INTERVENTION

Standard of care (SOC): Antibiotics will be commenced at onset of fever and continued for a duration as per clinician's discretion, typically until resolution of fever, clinical recovery and ANC ≥200- 500 cells/mm3.

Interventions

Early antibiotic cessation alert DRUG

For all patients, antibiotics will be commenced at onset of fever. For those in the intervention arm an alert will fire in the electronic medical record once a patient is afebrile for 48-96 hours and clinically stable.

STOP - early discontinuation of empiric antibiotic therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients ( ≥18 years) who are receiving either:
• Conditioning chemotherapy for an autologous or allogeneic haematopoietic cell transplant or CAR T cell therapy, OR
• Induction remission chemotherapy for acute leukaemia,
• AND develop fever ( ≥38degC) between time of initiation of chemotherapy/conditioning administration and ANC recovery to ≥500 cells/mm3 post the ANC nadir,
• AND fever subsequently has settled (\<38degC) for ≥48 and \<96h hours.
• \[participants will be stratified into pre-neutropenic (ANC ≥500 cells/mm3) and neutropenic (ANC\<500 cells/mm3) strata based on ANC level at 48 hours post fever onset, as per international consensus definition of neutropenic fever\]

You may not qualify if:

• \- Prolonged fever prior to defervescence (documented daily temperature ≥38.0°C for ≥ 5 days)
• Documented positive blood culture for bacteria since onset of fever episode and prior to randomisation
• Documented other infection (clinically or microbiologically defined) requiring antibacterial treatment
• Grade 2 or higher mucositis (WHO) or neutropenic enterocolitis
• Clinically unstable and/or admission to ICU at time of potential randomization
• Within 28 days of last randomization
• Prior randomization during current chemotherapy/conditioning cycle
• Pregnant or breastfeeding
• Currently being treated for CRS Grade 3 or 4, and/or ICANS Grade 3 or 4 (defined as per ASTCT Consensus Guidelines, Lee et al)

Sponsors & Collaborators

• Peter MacCallum Cancer Centre, Australia: lead
• Melbourne Health: collaborator

Study Sites (2)

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

RECRUITING

Royal Melbourne Hospital

Melbourne, Victoria, 3050, Australia

RECRUITING

MeSH Terms

Conditions

Leukemia; Bacterial Infections; Febrile Neutropenia

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bacterial Infections and Mycoses; Infections; Neutropenia; Agranulocytosis; Leukopenia; Cytopenia; Leukocyte Disorders

Study Officials

• Abby P Douglas, MBBS PhD FRACP

  Peter MacCallum Cancer Centre; National Centre for Infections in Cancer

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Principal Investigator

CONTACT

+61448503643; infectiousdiseases.clinicaltrials@petermac.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Intervention: Early discontinuation of empiric antibiotic therapy: ceasing antibiotics upon meeting all inclusion and no exclusion criteria Control: Standard of care: Continuing empiric antibiotics beyond resolution of fever for at least 96 hours and otherwise as per clinician's discretion (typically recovery of absolute neutrophil count (ANC) to \>200 cells/mm3)

Study Record Dates

• First Submitted: April 21, 2025
• First Posted: July 4, 2025
• Study Start: December 3, 2025
• Primary Completion (Estimated): December 5, 2027
• Study Completion (Estimated): February 5, 2028
• Last Updated: December 15, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2)