Early Versus Late Stopping of Antibiotics in Adults With High-risk Hematological Malignancies/Receiving Cellular Therapies and Fever
Early Versus Late Stopping of Antibiotics in Adults With High Risk Haematological Malignancies/Receiving Cellular Therapies and Fever (ELSA- Adult)
Peter MacCallum Cancer Centre, Australia
214 participants
Dec 3, 2025
INTERVENTIONAL
Conditions
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.
Eligibility
Inclusion Criteria6
- 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.
- \[participants will be stratified into pre-neutropenic (ANC ≥500 cells/mm3) and neutropenic (ANC\<500 cells/mm3) strata based on ANC level at 48 hours post fever onset, as per international consensus definition of neutropenic fever\]
Exclusion Criteria9
- \- 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)
Interventions
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.
Locations(2)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT07051525