Fungal infection following treatment for acute myeloid leukaemia (AML), high risk myelodysplasia (HRMDS), and acute lymphoblastic leukaemia (ALL) Infections and Infestations
Conditions
Interventions
Current interventions as of 26/02/2025:
Trial design:
The trial is designed as a multicentre, 404-patient, randomised controlled trial with parallel groups, of a biomarker-based antifungal stewardsh
Sponsors
Hull University Teaching Hospitals NHS Trust
Eligibility
Sex/Gender
All
Age
16 Years to 120 Years
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 26/02/2025: 1. Aged =16 years 2. Diagnosis of new, or relapsed, acute leukaemia or haematological disorder judged to need chemotherapy by the patient’s clinical care team. Eligible conditions include acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), high-risk myelodysplastic syndrome (HRMDS), or AML transformation of a myeloproliferative neoplasm (tMPN). 3. The patient is expected to have prolonged neutropenia related to chemotherapy which would mandate either antifungal prophylaxis and/or systematic invasive fungal infection biomarker monitoring (at least weekly). 4. Patient is willing and able to give informed consent for participation in the study _____ Previous inclusion criteria as of 26/05/2023: 1. Aged =16 years 2. Diagnosis of new, or relapsed, acute leukaemia or haematological disorder judged to need intensive chemotherapy by the patient’s clinical care team. Eligible conditions include acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), high-risk myelodysplastic syndrome (HRMDS), or AML transformation of a myeloproliferative neoplasm (tMPN). 3. The patient is expected to have prolonged neutropenia related to intensive chemotherapy which would mandate either antifungal prophylaxis and/or systematic invasive fungal infection biomarker monitoring (at least weekly). 4. Patient is willing and able to give informed consent for participation in the study _____ Previous inclusion criteria: 1. Aged =16 years 2. New diagnosis of, or relapsed, acute myeloid leukaemia (AML; according to WHO classification), acute lymphoblastic leukaemia (ALL), or high-risk myelodysplasic syndrome (HRMDS) judged to need intensive chemotherapy by the patient’s clinical care team 3. The patient is expected to have prolonged neutropenia (=10 days) because of their intensive chemotherapy 4. Patient is willing and able to give informed consent for participation in the study
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 26/02/2025: 1. Previous proven or probable invasive fungal infection (IFI) (according to the EORTC/MSG criteria). (I.e. this would not include previously treated cutaneous or other non-invasive infection, etc. If there is doubt about eligibility, please discuss with the local PI / research team and, if required, the central trial team / Chief Investigators). 2. Contraindication to all potential prophylactic antifungal agents (i.e. cannot be prescribed any recognised anti-Aspergillus agent as prophylaxis) 3. Planned chemotherapy using any regimen that mandates the use of systemic antifungal medication 4. Received > 72 hours of systemic mould-acting antifungal prophylaxis or therapy, or biomarker monitoring for IFI, prior to trial enrolment 5. Commenced the first cycle of chemotherapy > 72 hours prior to trial enrolment 6. Current diagnosis of prolonged (> 72 hours) neutropenic fever 7. Pregnancy _____ Previous exclusion criteria as of 24/04/2024: 1. Previous proven or probable invasive fungal infection (IFI) (according to the EORTC/MSG criteria). (I.e. this would not include previously treated cutaneous or other non-invasive infection, etc. If there is doubt about eligibility, please discuss with the local PI/research team and, if required, the central trial team / Chief Investigators). 2. Contraindication to all potential prophylactic antifungal agents (i.e. cannot be prescribed any recognised anti-Aspergillus agent as prophylaxis) 3. Planned chemotherapy using any regimen that mandates the use of systemic antifungal medication (i.e.Venetoclax-based regimens) 4. Received > 72 hours of systemic mould-acting antifungal prophylaxis or therapy, or biomarker monitoring for IFI, prior to trial enrolment 5. Commenced the first cycle of chemotherapy > 72 hours prior to trial enrolment 6. Current diagnosis of prolonged (> 72 hours) neutropenic fever 7. Pregnancy _____ Previous exclusion criteria as of 26/05/2023: 1. Previous proven or probable invasive fungal infection (IFI) 2. Contraindication to all potential prophylactic antifungal agents (i.e. cannot be prescribed any recognised anti-Aspergillus agent as prophylaxis) 3. Planned chemotherapy using any regimen that mandates the use of systemic antifungal medication (i.e.Venetoclax-based regimens) 4. Commenced antifungal prophylaxis or biomarker monitoring for IFI 5. Commenced the first cycle of chemotherapy AND has entered the invasive fungal infection (IFI) at risk period according to the usual local standard of care (i.e. the period that normally mandates local IFIpreventi on measures such as antifungal prophylaxis and/or biomarker monitoring) 6. Current diagnosis of neutropenic fever 7. Pregnancy Previous exclusion criteria: 1. Previous proven or probable invasive fungal infection (IFI) 2. Contraindication to all potential prophylactic antifungal agents (i.e. cannot be prescribed any recognised anti-Aspergillus agent) 3. Current diagnosis of chemotherapy-related neutropenic fever 4. Pregnancy 5. Planned chemotherapy using a Venetoclax based regimen mandating posaconazole as a concurrent medication
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Antifungal (AF) exposure in the 12 months from recruitment, defined as receipt of =72 hours of therapeutic systemic AF, measured as a dichotomous variable (Yes/No) at 12 months 2. Health-related quality of life at 12 months post-randomisation measured using EuroQol 5 Dimensions (5L) Score (EQ-5D-5L) collected at 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 24/04/2024: 1. Total antifungal (AF) exposure in the 12 months from recruitment measured using the total Defined Daily Doses (DDD) and whole days of therapy of prophylactic and therapeutic AF use at 12 months 2. Probable/proven invasive fungal infection (IFI) measured using clinical assessment of probable and proven IFIs as per the consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group at 12 months 3. All-cause mortality, and invasive fungal infection (IFI) mortality measured using patient status data collected at 12 months 4. Invasive fungal infection (IFI) treatment outcomes measured using data on the outcome of IFI treatment (treatment given and completed with no relapse; treatment given and completed, but with relapse; ongoing treatment; and IFI-related mortality) collected at 12 months 5. Antifungal-associated adverse effects/events/complications, measured using the adverse event reporting procedure records, and/or from relevant follow-up case report forms as appropriate, between baseline and 12 months 6. Resource use measured using hospital care health service use (e.g. length of hospital inpatient stay, readmissions, and outpatient visits) and product cost data collected from hospital records on a monthly basis. 7. Episodes of neutropenic fever requiring hospital admission or outpatient management, measured using the standard ESMO Clinical Practice Guidelines definition at 12 months 8. Antifungal resistance in fungi (non-invasive and invasive) measured using fungi isolated from clinical specimens taken as part of routine care (additional samples will not be taken unless the patient has consented and the site is participating in additional sampling for storage/research) between baseline and 12 months. This will be reported to YTU for the 12 months from study recruitment. 9. Desirability of Outcome Ranking (DOOR) measured using | — |
Countries
England, Scotland, United Kingdom
Outcome results
None listed