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

Study ID
ACCL1131

Cancer Related
Yes

Healthy Volunteers
No

Study Sites

  • Children’s Medical Center (Dallas, Plano, Southlake)

Contact
Sophia Williams
214/648-6554
sophia.williams2@childrens.com

Principal Investigator
Victor Aquino, M.D.

Official Title

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)

Brief Overview


This randomized phase III trial studies how well caspofungin acetate works compared to
fluconazole or voriconazole in preventing fungal infections in patients following donor stem
cell transplant. Caspofungin acetate, fluconazole, and voriconazole may be effective in
preventing fungal infections in patients following donor stem cell transplant. It is not yet
known whether caspofungin acetate is more effective than fluconazole or voriconazole in
preventing fungal infections in patients following donor stem cell transplant.

Summary


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 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 hematopoietic stem cell transplantation (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.

Participant Eligibility


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