A Phase III Open-Label Trial of Caspofungin vs. Azole Prophylaxis for Patients at High-Risk for Invasive Fungal Infections (IFI) Following Allogeneic Hematopoietic Cell Transplantation (HCT)

Location:

Rochester, Minn.

Trial status:

Open for Enrollment

Why is this study being done?

PRIMARY OBJECTIVES: I. To determine if caspofungin acetate (caspofungin) 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 create a 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: This is a multicenter study. Patients are stratified by center's choice of azole (fluconazole vs voriconazole), age (>= 12 years vs < 12 years), and type of transplant (umbilical cord blood [UCB] donor vs non-UCB donor with ex vivo T-cell depletion vs non-UCB donor with standard pharmacological graft-versus-host disease prophylaxis). 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 hours of allogeneic hematopoietic stem cell transplantation (HSCT) 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 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 days 100-114.

Who is eligible to participate?

Inclusion Criteria: - The patient must be undergoing allogeneic hematopoietic cell transplantation (HCT) for treatment of a malignancy, bone marrow failure syndrome, or congenital immunodeficiency - The source for allogeneic stem cells (bone marrow, peripheral blood stem cells [PBSC], or umbilical cord blood) must be an unrelated donor or mismatched (≤ 7/8 at human leukocyte antigen [HLA]-A, B, C, and DR if bone marrow or PBSC; ≤ 5/6 at HLA-A, B, and DR if cord blood) family donor - 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 CT scan) during that time period to be eligible for enrollment - Age ≥ 3 months and < 21 years for patients receiving fluconazole as antifungal comparator - Age ≥ 2 years and < 21 years for patients receiving voriconazole as the antifungal comparator - ECOG scores of 0, 1 or 2 (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 OR 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 ≤ 1.5 times upper limit of normal (ULN) for age (unless the increase in bilirubin is attributable to Gilbert syndrome) - SGOT (AST) or SGPT (ALT) < 2.5 times ULN for age - Patients with a history of proven or probable invasive mold infection are not eligible - Patients with an incompletely treated invasive yeast infection are not eligible - Patients with a history of anidulafungin (echinocandin) or azole (fluconazole or voriconazole) 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 - Patients receiving treatment for an invasive fungal infection (IFI) are not eligible

Last updated:

2/5/2014

NCT ID:

NCT01503515

IRB Number:

13-001959