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, MN.

Trial status:

Open for Enrollment

Why is this study being done?

OBJECTIVES: Primary - 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 - To determine if prophylaxis with caspofungin will result in a lower incidence of proven or probable cases of invasive aspergillosis (IA) compared with fluconazole. - To determine if prophylaxis with caspofungin will result in improved survival compared to fluconazole. - To determine if prophylaxis with caspofungin will result in less empiric antifungal therapy compared to fluconazole. - To determine the sensitivity, specificity, and positive and negative predictive value of biweekly galactomannan (GM) and beta-D glucan testing in diagnosing IFI. - To test the association between single nucleotide polymorphisms (SNPs) in genes involved in innate immunity and proven or probable IFI. - 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 IV over 1 hour once daily (QD) beginning within 24-72 hours after the last dose of chemotherapy for each course and continuing until ANC > 100-500/μL, the next chemotherapy course begins, or patient meets any off-protocol criteria. - Arm II: Patients receive fluconazole IV over 2 hours or orally (PO) QD beginning within 24-72 hours after the last dose of chemotherapy for each course and continuing until ANC > 100-500/μL, the next chemotherapy course begins, or patient meets any off-protocol criteria. 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?

DISEASE CHARACTERISTICS: - 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 - Planned treatment as per COG-AAML0531 (including those in whom it is planned to not administer Intensification III) or AAML1031 for any diagnosis; either those following these treatment plans or those enrolled on AAML1031 are eligible - Patients with the following diagnoses are not eligible: - Acute promyelocytic leukemia (APL) - Down syndrome - Juvenile myelomonocytic leukemia (JMML) PATIENT CHARACTERISTICS: - Creatinine clearance or radioisotope GFR ≥ 70 mL/min 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 SGOT (AST) or SGPT (ALT) < 2.5 x ULN - Lactating patients must agree not to nurse a child while on this trial - Female patients of childbearing age must have a negative pregnancy test - Patients must agree to use an effective birth control method - Patients with a documented history of IFI within the previous 30 days are not eligible - Patients with a history of echinocandin or fluconazole hypersensitivity are not eligible PRIOR CONCURRENT THERAPY: - See Disease Characteristics - No other concurrent systemic antifungal therapy

Last updated:

5/30/2013

NCT ID:

NCT01307579

IRB Number:

11-007044