The Efficacy and Safety of Liposomal Amphotericin B 3-5mg/kg Combined With Posaconazole/Isavuconazole for the Treatment of Mucormycosis in Patients With Hematologic Malignancies
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 9
- 主要终点
- Composite Response Rate at End of liposomal amphotericin B (L-AmB) (3-5 mg/kg/day IV) Therapy
研究概览
简要总结
This clinical trial, a single-arm prospective study, aims to evaluate the efficacy and safety of liposomal amphotericin B (3-5 mg/kg/day) combined with posaconazole/isavuconazole in treating adult patients with malignant hematological diseases complicated by mucormycosis. The primary objectives are to determine the proportion of patients achieving complete or partial resolution of mucormycosis symptoms and to identify prognostic factors influencing survival outcomes. Participants will receive the combination therapy, undergo regular monitoring of symptoms, adverse events, and disease progression via radiological and laboratory assessments, and complete follow-up visits to track long-term survival. The study will analyze composite response rates, treatment-related adverse events, and survival data to refine therapeutic strategies for this high-risk population.
详细描述
This research aims to test whether combining two antifungal medications-liposomal amphotericin B (given through an IV) and either posaconazole or isavuconazole (available as IV or oral pills)-can effectively and safely treat adults with blood cancers (like leukemia or lymphoma) who develop a severe fungal infection called mucormycosis. Current guidelines often recommend amphotericin B-based therapies, but optimal dosing, combinations, and treatment duration remain unclear. This study will provide critical data on whether a regimen of liposomal amphotericin B (3-5 mg/kg/day) paired with newer antifungals (posaconazole/isavuconazole) can enhance outcomes. It will also identify which patient characteristics (e.g., age, cancer type, recovery speed) most strongly affect survival, helping doctors personalize care.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of a hematologic malignancy (e.g., leukemia, lymphoma, myelodysplastic syndrome).
- •Proven, probable, or possible invasive mucormycosis according to the 2019 European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria.
- •Age ≥18 years and ≤65 years at enrollment.
- •Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0-
- •No clinically significant organ dysfunction (e.g., renal, hepatic, cardiac) at screening that would preclude protocol-defined therapies.
- •Ability to understand the study procedures and provide voluntary written informed consent.
排除标准
- •Prior treatment with non-liposomal amphotericin B formulations (e.g., amphotericin B deoxycholate) for ≥4 days.
- •Documented hypersensitivity, severe immediate allergic reaction, or intolerance to liposomal amphotericin B.
- •History of a second malignancy (other than the index hematologic malignancy) treated within the past 3 years.
- •Active HIV infection, hepatitis B virus (HBV) infection (HBsAg-positive), hepatitis C virus (HCV) infection (RNA-positive), or syphilis.
- •Psychiatric disorders, cognitive impairment, or other conditions impairing compliance with study procedures or assessments.
- •Pregnant females, breastfeeding females, or individuals of reproductive potential unwilling to use effective contraception during treatment and for ≥3 months post-therapy.
- •Serum creatinine ≥2.0 × upper limit of normal (ULN).
- •Liver transaminases (ALT/AST) or alkaline phosphatase ≥5.0 × ULN.
- •Total bilirubin ≥3.0 × ULN (isolated bilirubin ≥3.0 × ULN is permitted if due to Gilbert's syndrome or hemolysis).
- •Patients deemed ineligible by the investigator due to medical, ethical, or logistical reasons.
研究组 & 干预措施
Single-arm,multi-center real-world study
This is a single-arm study where all participants receive the same treatment. Participants will be treated with a combination antifungal regimen comprising:
- Liposomal Amphotericin B (L-AmB):
Dose: 3-5 mg/kg/day administered intravenously (IV). Duration: Daily infusions until clinical stability, with adjustments permitted based on disease severity and tolerability. 2. Posaconazole or Isavuconazole:
Formulations: Oral tablets or intravenous (IV) formulations. Dosing: Loading dose: As per product labeling. Maintenance dose: 300 mg (posaconazole) or 200 mg (isavuconazole) once daily. Duration: Continued orally after discontinuation of L-AmB, per clinical judgment.
干预措施: liposomal amphotericin B (3-5 mg/kg/day) combined with posaconazole/isavuconazole (Drug)
结局指标
主要结局
Composite Response Rate at End of liposomal amphotericin B (L-AmB) (3-5 mg/kg/day IV) Therapy
时间窗: Assessed immediately after discontinuation of liposomal amphotericin B therapy.
The proportion of participants achieving a composite response, defined as the complete or partial resolution of mucormycosis-related clinical symptoms, radiological improvement (e.g., reduction in lesion size on CT/MRI), and microbiological clearance (e.g., negative fungal cultures or biomarkers).
次要结局
- Time to Favorable Overall Response(From date of enrollment until the date of first documented response, assessed up to 84 dsys.)
- Length of Hospitalization(Measured immediately after the intervention)
- Safety and Tolerability Profile(Measured immediately after the intervention)
- Survival Rate at Key Time Points(Day 84)