Invasive Fungal Disease
Conditions
Keywords
Breakthrough fungal infection, Invasive fungal disease, Triazole prophylaxis, Amphotericin B, Hematological diseases
Brief summary
The goal of this clinical trial is to learn if amphotericin B works to treat breakthrough invasive fungal disease (IFD) in patients with hematological diseases who have received azole-based prophylaxis. It will also learn about the safety of amphotericin B in this population. The main questions it aims to answer are: 1. What is the overall response rate (complete remission + partial remission) of amphotericin B in treating breakthrough IFD after azole prophylaxis? 2. What medical problems do participants have when taking amphotericin B? 3. What is the 6-week (42-day) overall survival rate after starting treatment? This is a single-arm, prospective study. Participants will: 1. Receive intravenous liposomal amphotericin B (3-5 mg/kg daily) for 4-6 weeks. 2. Undergo weekly clinical and laboratory assessments, including serum G/GM tests, microbiology tests, and imaging (CT) at 2, 4, and 6 weeks. 3. Have safety monitoring including liver and kidney function, electrolytes, and ECG. 4. Be followed for treatment response and survival.
Interventions
DRUGAmphotericin B
Amphotericin B is a polyene antifungal drug used to treat breakthrough fungal infections. The dosage and duration will be determined based on pathogen results and clinical guidelines.
Sponsors
Peking University People's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years old. 2. Diagnosed with hematological diseases and receiving triazole prophylaxis. 3. Confirmed or suspected breakthrough invasive fungal disease (IFD) according to EORTC/MSG 2020 criteria. 4. Able to understand and sign the informed consent form voluntarily.
Exclusion criteria
1. Severe liver or renal dysfunction (ALT/AST \> 3×ULN, Cr \> 2×ULN). 2. Known allergy to amphotericin B or any component of the study drug. 3. Pregnant or lactating women. 4. Severe underlying diseases with expected survival \< 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate of Antifungal Therapy at 6 Weeks (42 Days) | 6 weeks (42 days) after treatment initiation | The overall response rate will be assessed at 6 weeks (42 days) after the initiation of amphotericin B treatment, evaluated according to the EORTC/MSG 2020 criteria for invasive fungal disease, including complete response, partial response, stable disease, and progressive disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival Rate at 6 Weeks | 6 weeks (42 days) after treatment initiation | Proportion of participants alive at 6 weeks (42 days) after initiation of amphotericin B therapy. |
| Change in serum G test level | From enrollment to the end of 6-week treatment | Change from baseline in serum (1,3)-β-D-glucan level. Unit of measure: pg/mL. |
| Change in serum GM test level | From enrollment to the end of 6-week treatment | Change from baseline in serum galactomannan test value. Unit of measure: ug/L. |
| Microbiological clearance | From enrollment to the end of 6-week treatment | Proportion of participants with negative conversion of baseline positive microbiological evidence (e.g., blood culture, sputum culture, mNGS, or site smear/culture). |
| Change in chest CT findings | Baseline to 6 weeks after treatment initiation | Change from baseline in chest CT lesion characteristics (e.g., reduction in size, new lesions, complete resolution). |
| Proportion of participants with treatment-emergent adverse events (AEs) | From first dose to 30 days after last dose. | Proportion of participants experiencing any AE, graded according to WHO toxicity criteria (grade 3 or higher AEs leading to drug discontinuation). |
| Proportion of participants discontinuing amphotericin B due to adverse events | During treatment period (up to 6 weeks). | Proportion of participants who permanently stop amphotericin B because of any AE. |
| Change in serum alanine aminotransferase (ALT) | Baseline to end of treatment up to 6 weeks (twice weekly). | Change from baseline in ALT level. Unit of measure: U/L. |
| Change in serum aspartate aminotransferase (AST) | Baseline to end of treatment up to 6 weeks (twice weekly). | Change from baseline in AST level. Unit of measure: U/L. |
| Change in serum total bilirubin | Baseline to end of treatment up to 6 weeks (twice weekly). | Change from baseline in total bilirubin level. Unit of measure: μmol/L. |
| Change in serum creatinine | Baseline to end of treatment up to 6 weeks (twice weekly). | Description: Change from baseline in serum creatinine level. Unit of measure: μmol/L. |
| Change in serum electrolyte levels (potassium, sodium, calcium, magnesium) | Baseline to end of treatment up to 6 weeks (twice weekly). | Change from baseline in serum levels of potassium, sodium, calcium, and magnesium. Each electrolyte will be reported separately as absolute change (mmol/L) from baseline. |
| Change in electrocardiogram (ECG) findings | Baseline to end of treatment up to 6 weeks (weekly). | Change from baseline in ECG parameters (e.g., QTc interval). |
Countries
China
Contacts
CONTACTRui Ma
Outcome results
None listed