Caspofungin Versus Fluconazole in Preventing Invasive Fungal Infections (IFI) in Patients Undergoing Chemotherapy for Acute Myeloid Leukemia
Condition: Acute Myeloid Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Childhood Acute Monoblastic Leukemia; Childhood Acute Monocytic Leukemia; Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myeloid Leukemia With Maturation; Childhood Acute Myeloid Leukemia With Minimal Differentiation; Childhood Acute Myeloid Leukemia Without Maturation; Childhood Acute Myelomonocytic Leukemia; Fungal Infection; Myeloid Neoplasm; Neutropenia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Myeloid Neoplasm
MeSH terms: Infections; Communicable Diseases; Mycoses; Invasive Fungal Infections; Leukemia; Neoplasms; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Myelomonocytic, Chronic; Leukemia, Monocytic, Acute; Neutropenia; Recurrence
Study type: Interventional
Phase: Phase 3

Summary: 
      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.
    

Detailed description: 
      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.

      ARM I: Patients receive caspofungin acetate intravenously (IV) over one 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 within
      24-72 hours following the last dose of chemotherapy for each course.

      Protocol prophylaxis was continued in both arms, until ANC increased to > 100-500/uL
      following the nadir or the next chemotherapy course began. Prophylaxis was given for all
      courses of planned AML chemotherapy or until the patient met one of the following
      off-protocol therapy criteria: development of proven or probable IFI according to
      institutional diagnosis, initiation of conditioning for hematopoietic cell transplantation,
      initiation of a new chemotherapy regimen for relapsed or refractory AML, refusal of further
      protocol therapy by patient, parent or guardian, or physician determines it is in the best
      interest of the patient.

      Regardless of duration of prophylaxis, subjects in both arms are monitored for IFI until the
      earliest of the following criteria is met: two weeks after recovery of neutropenia following
      the last planned AML chemotherapy course, initiation of conditioning for hematopoietic cell
      transplantation, initiation of a new chemotherapy regimen for relapsed or refractory AML,
      withdrawal of consent for any further data submission, or death.

      Patients were followed for overall survival up to two years from enrollment.
    

Intervention name(s): Caspofungin Acetate; Fluconazole; Laboratory Biomarker Analysis
Intervention type(s): Drug; Drug; Other
Intervention description(s): Given IV; Given IV or PO; Correlative studies
Other intervention name(s): Cancidas; Diflucan
Intervention MeSH terms: Fluconazole; Caspofungin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Supportive Care
Keywords: Pediatrics; leukemia; invasive fungal infection