A Randomized Open-Label Trial of Caspofungin Versus Fluconazole to Prevent Invasive Fungal Infections in Children Undergoing Chemotherapy for Acute Myeloid Leukemia (AML)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 517
- 试验地点
- 179
- 主要终点
- Percentage of Participants With Proven or Probable Invasive Fungal Infections (IFI)
研究概览
简要总结
This randomized phase III trial compares the effectiveness of caspofungin to fluconazole in preventing invasive fungal infections in patients receiving chemotherapy for acute myeloid leukemia (AML). Antifungal prophylaxis is considered standard of care in children and adults with prolonged neutropenia after chemotherapy for AML however the ideal antifungal agent for prophylaxis in children is not known. Caspofungin has activity against yeast and some molds while fluconazole coverage is limited to just yeasts. Adult randomized trials suggest that agents with activity against yeasts and molds are more effective than those with just activity against yeasts. There are limited data to answer this comparative question in children. This study will establish much needed pediatric data to guide clinical decision making on optimal antifungal prophylaxis.
详细描述
PRIMARY OBJECTIVES:
I. To determine if prophylaxis with caspofungin administered during periods of neutropenia following chemotherapy for acute myeloid leukemia (AML) is associated with a lower incidence of proven or probable invasive fungal infections (IFI) compared with fluconazole.
SECONDARY OBJECTIVES:
I. To determine if prophylaxis with caspofungin will result in a lower incidence of proven or probable cases of invasive aspergillosis (IA) compared with fluconazole. (Clinical) II. To determine if prophylaxis with caspofungin will result in improved survival compared to fluconazole. (Clinical) III. To determine if prophylaxis with caspofungin will result in less empiric antifungal therapy compared to fluconazole. (Clinical) IV. To determine the sensitivity, specificity, and positive and negative predictive value of biweekly galactomannan (GM) and beta-D glucan testing in diagnosing IFI. (Biological) V. To test the association between single nucleotide polymorphisms (SNPs) in genes involved in innate immunity and proven or probable IFI. (Biological) VI. To develop predictive models of IFI using SNP in genes involved in immunity and clinical covariates. (Biological)
OUTLINE: Patients are randomized to one of two treatment arms during their first chemotherapy course for AML.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 3 Months 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have one of the following diagnoses and/or treatment plans:
- •Newly diagnosed de novo AML
- •First or subsequent relapse of AML
- •Secondary AML
- •Treatment with institutional standard AML therapy in those without AML (for example, myelodysplastic syndrome, bone marrow blasts > 5% or biphenotypia)
- •Note: Patients with a history of prolonged antifungal therapy (example, relapsed AML) are eligible
- •Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 OR a serum creatinine based on age/gender as follows:
- •=< 0.4 mg/dL (age 1 month to < 6 months)
- •=< 0.5 mg/dL (age 6 months to < 1 year)
- •=< 0.6 mg/dL (age 1 to < 2 years)
- •=< 0.8 mg/dL (age 2 to < 6 years)
- •=< 1 mg/dL (age 6 to < 10 years)
- •=< 1.2 mg/dL (age 10 to < 13 years)
- •=< 1.4 mg/dL (females age >= 13 years)
- •=< 1.5 mg/dL (males age 13 to < 16 years)
- •=< 1.7 mg/dL (males age >= 16 years)
- •Total bilirubin =< 1.5 x upper limit of normal (ULN) for age AND Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x ULN for age
- •All patients and/or their parents or legal guardians must sign a written informed consent
排除标准
- •Patients with the following diagnoses are not eligible:
- •Acute promyelocytic leukemia (APL)
- •Down syndrome
- •Juvenile myelomonocytic leukemia (JMML)
- •Patients with a documented history of invasive fungal infection (IFI) within the previous 30 days are not eligible
- •Patients with a history of echinocandin or fluconazole hypersensitivity are not eligible
- •Patients receiving treatment for an IFI are not eligible
- •Female patients of childbearing age must have a negative pregnancy test
- •Patients must agree to use an effective birth control method
- •Lactating patients must agree not to nurse a child while on this trial
研究组 & 干预措施
Arm I (caspofungin acetate)
Patients receive caspofungin acetate IV over one hour QD beginning within 24-72 hours following the last dose of chemotherapy for each course. and continuing until ANC > 100-500/uL following the nadir or the next chemotherapy course begins.
干预措施: Caspofungin Acetate (Drug)
Arm I (caspofungin acetate)
Patients receive caspofungin acetate IV over one hour QD beginning within 24-72 hours following the last dose of chemotherapy for each course. and continuing until ANC > 100-500/uL following the nadir or the next chemotherapy course begins.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (fluconazole)
Patients receive fluconazole IV over 1-2 hours or PO QD beginning within 24-72 hours following the last dose of chemotherapy for each course.
干预措施: Fluconazole (Drug)
Arm II (fluconazole)
Patients receive fluconazole IV over 1-2 hours or PO QD beginning within 24-72 hours following the last dose of chemotherapy for each course.
干预措施: Laboratory Biomarker Analysis (Other)
结局指标
主要结局
Percentage of Participants With Proven or Probable Invasive Fungal Infections (IFI)
时间窗: Up to 5 months since enrollment
Proven or probable IFI is defined according to criteria developed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG).
次要结局
- Percentage of Participants That Need Empiric Antifungal Therapy(Up to 5 months since enrollment)
- Percentage of Participants With Proven or Probable Invasive Aspergillosis (IA)(Up to 5 months since enrollment)
- Overall Survival(Up to 2 years post enrollment)