Caspofungin Acetate, Fluconazole, or Voriconazole in Preventing Fungal Infections in Patients Following Donor Stem Cell Transplant

PRIMARY OBJECTIVES:

I. To determine if caspofungin (caspofungin acetate) is associated with a lower incidence of
proven/probable invasive fungal infections (IFI) during the first 42 days following
allogeneic hematopoietic cell transplantation (HCT) at high-risk for IFI compared with azole
(fluconazole or voriconazole) prophylaxis.

SECONDARY OBJECTIVES:

I. To determine if caspofungin is associated with a lower incidence of proven/probable IFI
during the first 100 days following high-risk allogeneic HCT compared with azole (fluconazole
or voriconazole) prophylaxis. (Exploratory) II. To determine if caspofungin is associated
with a lower incidence of proven/probable IFI during the first 42 and 100 days following
high-risk allogeneic HCT compared with fluconazole prophylaxis. (Exploratory) III. To
determine if caspofungin is associated with a lower incidence of proven/probable IFI during
the first 42 and 100 days following high-risk allogeneic HCT compared with voriconazole
prophylaxis. (Exploratory) IV. To determine if caspofungin is associated with a superior
fungal-free survival (FFS) (time to death or proven/probable IFI) at 42 and 100 days
following high-risk allogeneic HCT compared with azole prophylaxis. (Exploratory) V. To
describe the effect that caspofungin and azoles have on the incidence and severity of acute
graft-versus-host disease (GVHD). (Exploratory) VI. To define the test characteristics of
weekly Fungitell assay testing for identifying IFI in pediatric hematopoietic stem cell
transplantation (HSCT) recipients receiving antifungal prophylaxis during the post-transplant
neutropenic period. (Exploratory) VII. To create a deoxyribonucleic acid (DNA) specimen bank
in anticipation of the development of biology correlative studies exploring the relationship
between IFI and single nucleotide polymorphisms (SNPs) of genes involved in immunity.
(Exploratory)

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 hours of allogeneic HSCT (day -1 or 0) and continuing until day 42 in the
absence of invasive fungal infections or disease progression.

ARM II: Patients receive fluconazole IV over 1-2 hours QD or orally (PO) QD; or voriconazole
IV over 1-2 hours QD or PO twice daily (BID) beginning within 24 hours of allogeneic HSCT
(day -1 or 0) and continuing until day 42 in the absence of invasive fungal infections or
disease progression.

After completion of study treatment, patients are followed up until day 100.

Inclusion Criteria:

- Age

- For centers that will use fluconazole as the antifungal comparator:

- Age >= 3 months and < 21 years

- For centers that will use voriconazole as the antifungal comparator:

- Age >= 2 years and < 21 years

- The patient must be undergoing allogeneic HCT from any donor (including matched
related) with any stem cell source for any underlying condition

- Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1 or 2; use Karnofsky for patients > 16 years of age and
Lansky for patients =< 16 years of age

- 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 (1 month to < 6 months of age)

- 0.5 mg/dL (6 months to < 1 year of age)

- 0.6 mg/dL (1 to < 2 years of age)

- 0.8 mg/dL (2 to < 6 years of age)

- 1.0 mg/dL (6 to < 10 years of age)

- 1.2 mg/dL (10 to < 13 years of age)

- 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)

- 1.7 mg/dL (male) or 1.4 mg/dL (female) (>= 16 years of age)

- Total bilirubin < 2.5 mg/dL unless the increase in bilirubin is attributable to
Gilbert?s syndrome

- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or
serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 5 x
upper limit of normal (ULN) for age

- All patients and/or their parents or legal guardians must sign a written informed
consent

- All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met

Exclusion Criteria:

- Within 90 days of enrollment:

- Patients with a proven or probable invasive mold infection are not eligible

- Patients with an incompletely treated invasive yeast infection are not eligible

- Patients with an elevated galactomannan level (>= 0.5 index) within 30 days prior
to time of enrollment (if performed) must have a full evaluation for invasive
aspergillosis (including a negative chest computed tomography [CT] scan) during
that time period to be eligible for enrollment

- Patients receiving treatment for an IFI are not eligible

- Patients with a history of echinocandin or azole hypersensitivity are not eligible

- Female patients of childbearing potential are not eligible unless a negative pregnancy
test result has been obtained

- Sexually active patients of reproductive potential are not eligible unless they have
agreed to use an effective contraceptive method for the duration of their study
participation

- Lactating females are not eligible unless they have agreed not to breastfeed their
infants