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)
N/A
20 Years
Both
Fungal Infection, Hematopoietic/Lymphoid Cancer, Nonneoplastic Condition, Unspecified Childhood Solid Tumor, Protocol Specific
Trial Information
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)
OBJECTIVES:
Primary
- 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
- 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)
- 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)
- 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)
- 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)
- To describe the effect that caspofungin and azoles have on the incidence and severity
of acute graft-versus-host disease (GVHD). (Exploratory)
- To determine the diagnostic performance characteristics of galactomannan and beta-D
glucan testing in the setting of different anti-fungal prophylactic strategies for the
early diagnoses of IFI following high-risk allogeneic HCT. (Exploratory)
- 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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- 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
PATIENT CHARACTERISTICS:
- 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
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Patients receiving treatment for an invasive fungal infection (IFI) are not eligible
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Supportive Care
Outcome Measure:
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)
Outcome Description:
Kaplan-Meier curves will be used to estimate the time to onset of proven/probable IFI for patients randomized to the 2 arms. Log rank test will be used to compare the incidence of IFI between the 2 randomized arms during the at-risk period.
Outcome Time Frame:
Up to 42 days following stem cell infusion
Safety Issue:
No
Principal Investigator
Christopher C. Dvorak, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
UCSF Medical Center at Parnassus
Authority:
United States: Federal Government
Study ID:
ACCL1131
NCT ID:
NCT01503515
Start Date:
March 2013
Completion Date:
Related Keywords:
- Fungal Infection
- Hematopoietic/Lymphoid Cancer
- Nonneoplastic Condition
- Unspecified Childhood Solid Tumor, Protocol Specific
- fungal infection
- unspecified childhood solid tumor, protocol specific
- hematopoietic/lymphoid cancer
- congenital combined immunodeficiency
- Mycoses
Name | Location |
|---|---|
| Children's Oncology Group | Arcadia, California 91006-3776 |
