Low-Dose Liposomal Amphotericin B for Invasive Fungal Infection Prophylaxis in Neutropenic Children

Evaluation of Efficacy and Safety of Low-Dose Liposomal Amphotericin B in Prophylaxis of Invasive Fungal Infections Among Children With Prolonged Neutropenia: A Clinical Study

This is a single-center, single-arm, observational clinical study evaluating the efficacy and safety of low-dose liposomal amphotericin B (1 mg/kg/day, intravenous, once daily) for the prevention of invasive fungal infections in children aged 3-17 years with hematological malignancies who develop prolonged neutropenia (absolute neutrophil count ≤ 0.5×10^9/L, expected to last > 7 days) and are at high risk for invasive fungal disease. Participants are those who, per the treating physician's routine clinical decision, have been initiated on liposomal amphotericin B prophylaxis at 1 mg/kg/day due to intolerance or toxicity to other antifungal agents. The primary outcome is the incidence of proven or probable invasive fungal disease. Secondary outcomes include incidence of pneumonia, persistent unexplained fever >4 days, use of additional systemic antifungal therapy, and adverse events. A total of 30 participants will be enrolled. Data will be collected at baseline, during treatment, and within 7 days after treatment completion.

Study Overview

• Status: Recruiting
• Conditions: Invasive Fungal Infections; Neutropenia; Thalassemia; Hematopoietic Stem Cell Transplantation; Graft vs Host Disease
• Intervention / Treatment: Drug: Liposomal Amphotericin B (LAmB)

Detailed Description

Invasive fungal disease (IFD) is a serious and life-threatening infection caused by pathogenic fungi such as Candida, Aspergillus, and Mucorales, commonly affecting immunocompromised patients with hematological malignancies and those undergoing hematopoietic stem cell transplantation. The incidence of IFD has increased significantly in recent years due to the use of intensive chemotherapy and immunosuppressive agents, which result in prolonged and profound neutropenia (absolute neutrophil count < 500/μL for ≥10 days). Effective antifungal prophylaxis is a critical strategy to reduce IFD-related morbidity and mortality in this high-risk population.

Liposomal amphotericin B (L-AmB) is a broad-spectrum antifungal agent with potent activity against most pathogenic fungi, including azole-resistant strains such as certain Aspergillus and Mucorales species. It is recommended by multiple guidelines as a first-line treatment for candidemia, invasive aspergillosis, and mucormycosis. However, its optimal prophylactic dosing regimen remains unclear, with published studies using widely varying regimens ranging from fixed low-dose (e.g., 50 mg every other day) to intermittent high-dose schedules (e.g., 5 mg/kg twice weekly).

This study proposes a novel prophylactic regimen of L-AmB at a fixed low dose of 50 mg/day (approximately 1 mg/kg/day) administered intravenously once daily. This regimen is designed to provide sustained, continuous drug exposure throughout the high-risk neutropenic period, potentially offering superior protection compared to intermittent high-dose schedules while maintaining a favorable safety profile.

This is a single-center, single-arm, observational clinical study. Participants will be children aged 3-17 years with hematological malignancies who meet the NCCN 2025 V1 guideline criteria for high-risk IFD, including allogeneic hematopoietic stem cell transplantation, autologous hematopoietic cell transplantation with mucosal damage, acute leukemia, grade 3/4 graft-versus-host disease, myelodysplastic syndrome, or other conditions with expected neutropenia >7 days. Participants must have been initiated on L-AmB prophylaxis at 1 mg/kg/day by the treating physician in routine clinical practice due to intolerance or toxicity to other antifungal agents. Key exclusion criteria include prior proven/probable IFD, active fungal infection at screening, significant hypokalemia, severe hepatic or renal impairment, and NYHA Class III/IV heart failure.

A total of 30 participants will be enrolled. Data will be collected at three time points: baseline (Day -3 to 0), treatment period (from Day 1 until the end of L-AmB therapy), and follow-up (within 7 days after treatment completion). Assessments include complete blood counts, serum biochemistry, imaging (chest CT), microbiological tests (G/GM tests, blood cultures, bronchoalveolar lavage fluid cultures or NGS), and recording of neutropenia episodes, fever, pneumonia, and adverse events. IFD diagnosis will be classified according to the Sixth Revised Edition of the Diagnostic Criteria and Treatment Principles for Invasive Fungal Disease in Patients with Hematological Malignancies.

The primary outcome is the incidence of proven or probable IFD. Secondary outcomes include: (1) incidence of pneumonia with no identified pathogen; (2) proportion of patients with persistent unexplained fever >4 days; (3) proportion of patients requiring additional systemic antifungal therapy; (4) discontinuation rate due to adverse effects or intolerance; and (5) incidence of adverse events graded according to CTCAE Version 5.0.

The study is expected to enroll patients from February 2026 to February 2027, with final data collection and analysis completed by March 2027. This study is approved by the institutional ethics committee and will be conducted in accordance with the Declaration of Helsinki. Informed consent will be obtained from all participants or their legal representatives.

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Xiaoyang Yang, MD; Phone Number: +86-13337647693; Email: y108108@126.com
• Study Contact Backup: Name: Guang Cheng, MMed; Phone Number: +86-18077944163; Email: chengg4163@163.com

Study Locations

• China
  • Hainan
    • Haikou, Hainan, China, 570208
      • Recruiting
      • Haikou Affiliated Hospital of Central South University Xiangya School of Medicine
      • Contact: Xiaoyang Yang, MD; Phone Number: +86-13337647693; Email: y108108@126.com
      • Contact: Luyi Pang, MMed; Phone Number: +86-15737306070; Email: pangluyi2024@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Children aged 3-17 years with thalassemia or other hematological conditions who undergo allogeneic hematopoietic stem cell transplantation or other intensive therapies associated with prolonged neutropenia (>7 days), meet NCCN 2025 V1 high-risk criteria for invasive fungal disease, and have been initiated on liposomal amphotericin B prophylaxis at 1 mg/kg/day by the treating physician in routine clinical practice due to intolerance or toxicity to other antifungal agents.

Description

Inclusion Criteria:

• Age 3 to 17 years (inclusive), both sexes.
• Meets NCCN 2025 V1 guideline criteria for high-risk invasive fungal disease, including allogeneic hematopoietic stem cell transplantation, autologous hematopoietic cell transplantation with mucosal damage, acute leukemia, grade 3/4 graft-versus-host disease, myelodysplastic syndrome, lymphoma(a), multiple myeloma(a), chronic lymphocytic leukemia(a), treatment with purine analogues (fludarabine, clofarabine, nelarabine), chimeric antigen receptor (CAR) T-cell therapy, alemtuzumab therapy, with expected neutropenia >7 days(b) and accompanied by agranulocytosis.

Note (a): For these heterogeneous diseases, myeloablative therapy must be met; if neutropenia >7 days is not met, the patient should be excluded.

Note (b): Agranulocytosis is defined as absolute neutrophil count ≤0.5×10^9/L, or absolute neutrophil count ≤1×10^9/L with expected decline to ≤0.5×10^9/L within 48 hours.

• Assessed by the study physician as having high-risk for invasive fungal infection, intolerant or unable to use other antifungal agents due to toxicity or other reasons, and the treating physician has independently decided in routine clinical practice to initiate liposomal amphotericin B for antifungal prophylaxis for 3-5 days, with the selected dosage regimen of 1 mg/kg/day, intravenous, once daily.
• Patient or legally authorized representative has voluntarily signed the informed consent form.

Exclusion Criteria:

• Allergy to any component of liposomal amphotericin B, or development of serious adverse events during the initial 3-5 days of prophylactic use.
• Prior history of proven or probable invasive fungal disease (IFD).
• Presence of pneumonia, unexplained fever, or clinical/imaging evidence suggestive of or diagnosed as fungal infection during screening.
• Clinically significant hypokalemia (defined as serum potassium <3.2 mmol/L, or below the lower limit of normal while receiving digitalis therapy) that cannot be corrected before starting trial treatment.
• Hepatic dysfunction with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥5× upper limit of normal (ULN), or total bilirubin ≥3× ULN.
• Renal impairment requiring or currently undergoing hemodialysis or peritoneal dialysis.
• New York Heart Association (NYHA) Class III/IV heart failure.
• Positive for human immunodeficiency virus (HIV) antibody or Treponema pallidum hemagglutination assay (TPHA).
• Expected survival <3 months.
• Pregnant or breastfeeding women, or women of childbearing potential who are not using contraception and planning pregnancy.
• Any other condition that the investigator considers inappropriate for participation in the clinical trial.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Liposomal Amphotericin B Prophylaxis Group; Children with thalassemia undergoing allogeneic hematopoietic stem cell transplantation who meet high-risk criteria for invasive fungal disease per NCCN 2025 V1 guidelines, with expected neutropenia >7 days (absolute neutrophil count ≤0.5×10^9/L). Participants receive liposomal amphotericin B at 1 mg/kg/day, intravenous, once daily, as antifungal prophylaxis initiated by the treating physician in routine clinical practice due to intolerance or toxicity to other antifungal agents.

Drug: Liposomal Amphotericin B (LAmB); Liposomal amphotericin B at 1 mg/kg/day, administered intravenously once daily, for antifungal prophylaxis in children with prolonged neutropenia. Liposomal amphotericin B is a broad-spectrum polyene antifungal agent with activity against most pathogenic fungi, including Candida, Aspergillus, and Mucorales species. The liposomal formulation reduces nephrotoxicity compared to conventional amphotericin B deoxycholate while maintaining equivalent antifungal activity.; Other Names: L-AmB; Amphotericin B Liposome

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Proven or Probable Invasive Fungal Disease	Proven or probable invasive fungal disease (IFD) diagnosed according to the Sixth Revised Edition of the Diagnostic Criteria and Treatment Principles for Invasive Fungal Disease in Patients with Hematological Malignancies. Proven IFD requires histopathological evidence or positive culture from a sterile site. Probable IFD requires the presence of host factors, clinical features, and mycological evidence.	From baseline to 7 days after the end of antifungal prophylaxis treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Pneumonia With No Identified Pathogen	Incidence of pneumonia occurring during the study period with no pathogen identified by microbiological or molecular methods, including but not limited to blood cultures, bronchoalveolar lavage fluid cultures, and NGS.	From baseline to 7 days after the end of antifungal prophylaxis treatment
Proportion of Participants With Persistent Unexplained Fever >4 Days	Proportion of participants with persistent unexplained fever lasting more than 4 days during the study period. Unexplained fever is defined as fever without an identifiable infectious source after initial clinical evaluation.	From baseline to 7 days after the end of antifungal prophylaxis treatment
Proportion of Participants Requiring Additional Systemic Antifungal Therapy	Proportion of participants who require systemic antifungal therapy other than the study drug (low-dose liposomal amphotericin B) for suspected or confirmed fungal infection during the study period.	From baseline to 7 days after the end of antifungal prophylaxis treatment
Discontinuation Rate of Liposomal Amphotericin B Due to Adverse Effects or Intolerance	Proportion of participants who discontinue liposomal amphotericin B prophylaxis due to drug-related adverse effects or intolerance during the treatment period.	Throughout the treatment period (from Day 1 to the end of liposomal amphotericin B therapy)
Incidence of Adverse Events	Incidence of adverse events occurring during the study period, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Adverse events include laboratory abnormalities (serum creatinine elevation, hepatic enzyme elevation, hypokalemia) and clinical symptoms (infusion-related reactions, fever, chills, nausea, vomiting, etc.).	From baseline to 7 days after the end of antifungal prophylaxis treatment

Collaborators and Investigators

• Sponsor: Haikou Affiliated Hospital of Central South University Xiangya School of Medicine
• Investigators: Principal Investigator: Xiaoyang Yang, MD, Department of Hematology, Haikou People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2026
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: July 21, 2026
• First Submitted That Met QC Criteria: July 23, 2026
• First Posted (Actual): July 24, 2026

Study Record Updates

• Last Update Posted (Actual): July 24, 2026
• Last Update Submitted That Met QC Criteria: July 23, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Thalassemia; Neutropenia; Liposomal Amphotericin B; Allogeneic Hematopoietic Stem Cell Transplantation; Invasive Fungal Disease; Antifungal Prophylaxis
• Additional Relevant MeSH Terms: Cytopenia; Genetic Diseases, Inborn; Immune System Diseases; Infections; Leukocyte Disorders; Hematologic Diseases; Bacterial Infections and Mycoses; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Leukopenia; Agranulocytosis; Mycoses; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Invasive Fungal Infections; Thalassemia; Graft vs Host Disease; Neutropenia; Organic Chemicals; Macrolides; Lactones; Polyketides; Amphotericin B; liposomal amphotericin B
• Other Study ID Numbers: SC20260053

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: This is a single-center observational study with a small sample size of 30 pediatric participants. Individual participant data will not be shared because the study involves a vulnerable population (children with thalassemia undergoing allogeneic hematopoietic stem cell transplantation), and the research protocol did not include provisions for data sharing with external researchers. Furthermore, the study materials and records will be stored locally at the study site and will not be made publicly available to protect participant privacy, in accordance with the study's confidentiality and privacy protection requirements.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No