Clinical Trial: Caspofungin Acetate or Fluconazole in Preventing Invasive Fungal Infections in Patients With Acute Myeloid Leukemia Who Are Undergoing Chemotherapy

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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

Brief Summary: This randomized phase III trial studies caspofungin acetate to see how it works compared to fluconazole in preventing invasive fungal infections in patients with acute myeloid leukemia who are undergoing chemotherapy. Caspofungin acetate or fluconazole may help prevent fungal infections caused by chemotherapy. It is not yet known whether fluconazole is more effective than caspofungin acetate in preventing fungal infections in patients with acute myeloid leukemia who are undergoing chemotherapy.

Detailed Summary:

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. (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 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) > 100-500/uL following the nadir or the next chemotherapy course begins.

ARM II: Patients receive fluconazole IV over 1-2 hours or orally (PO) QD beginning
Sponsor: Children's Oncology Group

Current Primary Outcome: Time to development of proven or probable IFI, defined according to criteria developed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) [ Time Frame: Assessed up to 2 years ]

Evaluated using Kaplan-Meier analyses. Log rank test will be used to assess if there is any benefit associated with caspofungin acetate compared to fluconazole. Gray's test will be used to compare the cumulative incidence function between the 2 arms. Summary statistics such as means, standard deviations, medians, and ranges will be produced.


Original Primary Outcome: Development of proven or probable invasive fungal infections (IFI) defined according to criteria developed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG)

Current Secondary Outcome:

  • Time to development of proven or probably invasive aspergillosis (IA), defined according to the criteria developed by the EORTC/MSG [ Time Frame: Assessed up to 2 years ]
    Evaluated using Kaplan-Meier analyses. Log rank test will be used to assess if there is any benefit associated with caspofungin acetate compared to fluconazole. Gray's test will be used to compare the cumulative incidence function between the 2 arms. Summary statistics such as means, standard deviations, medians, and ranges will be produced.
  • Time to death due to any cause [ Time Frame: Assessed up to 2 years ]
    Standard survival analyses will be performed.
  • Total days of empiric antifungal therapy while a patient is receiving prophylaxis [ Time Frame: Up to 4 years ]
    Compared between the 2 arms using t-test or Wilcoxon rank sum test.


Original Secondary Outcome:

  • Development of proven or probably invasive aspergillosis (IA) defined according to the criteria developed by the EORTC/MSG
  • Death due to any cause
  • Need for empiric antifungal therapy defined as the institution of antifungal therapy while a patient is receiving prophylaxis
  • Results from galactomannan and beta-D glucan assays for the diagnosis of IFI or IA alone
  • Results of the genotyping assays for single nucleotide polymorphism analysis


Information By: Children's Oncology Group

Dates:
Date Received: March 1, 2011
Date Started: April 2011
Date Completion:
Last Updated: January 31, 2017
Last Verified: January 2017