A Randomized Open-Label Trial of Caspofungin Versus Fluconazole to Prevent Invasive Fungal Infections in Children Undergoing Chemotherapy for Acute Myeloid Leukemia (AML)

Location:

Rochester, Minn.

Trial status:
Open for Enrollment
Why is this study being done?

PRIMARY OBJECTIVES: I. To determine if prophylaxis with caspofungin (caspofungin acetate) 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. II. To determine if prophylaxis with caspofungin will result in improved survival compared to fluconazole. III. To determine if prophylaxis with caspofungin will result in less empiric antifungal therapy compared to fluconazole. IV. To determine the sensitivity, specificity, and positive and negative predictive value of biweekly galactomannan (GM) and beta-D glucan testing in diagnosing IFI. V. To test the association between single nucleotide polymorphisms (SNPs) in genes involved in innate immunity and proven or probable IFI. VI. To develop predictive models of IFI using SNP in genes involved in immunity and clinical covariates. OUTLINE: This is a multicenter study. Patients are stratified according to disease (de novo acute myeloid leukemia vs all other patients). Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive caspofungin acetate intravenously (IV) over 1 hour once daily (QD) beginning within 24-72 hours following the last dose of chemotherapy for each course and continuing until absolute neutrophil count (ANC) is 100-500/μL following the nadir or the next chemotherapy course begins. ARM II: Patients receive fluconazole IV over 2 hours or orally (PO) QD beginning within 24-72 hours following the last dose of chemotherapy for each course and continuing until absolute neutrophil count (ANC) is 100-500/μL following the nadir or the next chemotherapy course begins. In both arms, treatment continues in the absence of invasive fungal infections or disease progression. Blood samples may be collected twice weekly for antifungal antigen assays and at the end of course 1 for single nucleotide polymorphism analysis. After completion of study treatment, patients are followed up periodically for 2 years.

Who is eligible to participate?

Inclusion Criteria: - 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 - Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamic 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 Exclusion Criteria: - 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

Last updated:
2/5/2014
NCT ID:
NCT01307579
IRB Number:
11-007044