Amphotericin B for Breakthrough Fungal Infections After Triazole Prophylaxis in Hematological Patients

N/ANot Yet RecruitingNCT07559032

Peking University People's Hospital15 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Invasive Fungal Disease

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Overall Response Rate of Antifungal Therapy at 6 Weeks (42 Days)

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.

Time frame: 6 weeks (42 days) after treatment initiation

Secondary Outcomes

Overall Survival Rate at 6 Weeks

Proportion of participants alive at 6 weeks (42 days) after initiation of amphotericin B therapy.

Time frame: 6 weeks (42 days) after treatment initiation

Change in serum G test level

Change from baseline in serum (1,3)-β-D-glucan level. Unit of measure: pg/mL.

Time frame: From enrollment to the end of 6-week treatment

Change in serum GM test level

Change from baseline in serum galactomannan test value. Unit of measure: ug/L.

Time frame: From enrollment to the end of 6-week treatment

Microbiological clearance

Proportion of participants with negative conversion of baseline positive microbiological evidence (e.g., blood culture, sputum culture, mNGS, or site smear/culture).

Time frame: From enrollment to the end of 6-week treatment

Change in chest CT findings

Change from baseline in chest CT lesion characteristics (e.g., reduction in size, new lesions, complete resolution).

Time frame: Baseline to 6 weeks after treatment initiation

Proportion of participants with treatment-emergent adverse events (AEs)

Proportion of participants experiencing any AE, graded according to WHO toxicity criteria (grade 3 or higher AEs leading to drug discontinuation).

Time frame: From first dose to 30 days after last dose.

Proportion of participants discontinuing amphotericin B due to adverse events

Proportion of participants who permanently stop amphotericin B because of any AE.

Time frame: During treatment period (up to 6 weeks).

Change in serum alanine aminotransferase (ALT)

Change from baseline in ALT level. Unit of measure: U/L.