Caspofungin Acetate, Fluconazole, or Voriconazole in Preventing Fungal Infections in Patients Following Donor Stem Cell Transplant
- Conditions
- Fungal InfectionHematopoietic and Lymphoid Cell Neoplasm
- Interventions
- Registration Number
- NCT01503515
- Lead Sponsor
- Children's Oncology Group
- Brief Summary
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.
- Detailed Description
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.
EXPLORATORY 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 292
-
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
-
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I (caspofungin acetate) Caspofungin Acetate Patients receive caspofungin acetate 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 I (caspofungin acetate) Laboratory Biomarker Analysis Patients receive caspofungin acetate 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 (fluconazole or voriconazole) Laboratory Biomarker Analysis Patients receive fluconazole IV over 1-2 hours QD or PO QD; or voriconazole IV over 1-2 hours QD or PO 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. Arm II (fluconazole or voriconazole) Fluconazole Patients receive fluconazole IV over 1-2 hours QD or PO QD; or voriconazole IV over 1-2 hours QD or PO 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. Arm II (fluconazole or voriconazole) Voriconazole Patients receive fluconazole IV over 1-2 hours QD or PO QD; or voriconazole IV over 1-2 hours QD or PO 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.
- Primary Outcome Measures
Name Time Method 42-day-cumulative Incidence of Proven or Probable Invasive Fungal Infections (IFI) Up to 42 days following allogeneic HCT Kaplan-Meier curves will be used to estimate the 42- day-cumulative incidence of proven/probable IFI following allogeneic HCT for patients randomized to the 2 arms. Proven or probable IFI is defined according to criteria developed by the European Organization for Research and Treatment of Cancer (EORTC)/Mycoses Study Group (MSG).
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (49)
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸Dallas, Texas, United States
Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Rady Children's Hospital - San Diego
🇺🇸San Diego, California, United States
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
University of Minnesota/Masonic Cancer Center
🇺🇸Minneapolis, Minnesota, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Methodist Children's Hospital of South Texas
🇺🇸San Antonio, Texas, United States
Children's Hospital and Research Center at Oakland
🇺🇸Oakland, California, United States
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
Children's Hospital and Medical Center of Omaha
🇺🇸Omaha, Nebraska, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Phoenix Childrens Hospital
🇺🇸Phoenix, Arizona, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
UCSF Medical Center-Mission Bay
🇺🇸San Francisco, California, United States
Lucile Packard Children's Hospital Stanford University
🇺🇸Palo Alto, California, United States
UCSF Medical Center-Parnassus
🇺🇸San Francisco, California, United States
Nemours Children's Clinic-Jacksonville
🇺🇸Jacksonville, Florida, United States
Johns Hopkins All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Alfred I duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Children's Healthcare of Atlanta - Egleston
🇺🇸Atlanta, Georgia, United States
Kapiolani Medical Center for Women and Children
🇺🇸Honolulu, Hawaii, United States
University of Hawaii Cancer Center
🇺🇸Honolulu, Hawaii, United States
Children's Hospital New Orleans
🇺🇸New Orleans, Louisiana, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States
Children's Mercy Hospitals and Clinics
🇺🇸Kansas City, Missouri, United States
Helen DeVos Children's Hospital at Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Montefiore Medical Center - Moses Campus
🇺🇸Bronx, New York, United States
Children's Hospital Medical Center of Akron
🇺🇸Akron, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Medical City Dallas Hospital
🇺🇸Dallas, Texas, United States
Primary Children's Hospital
🇺🇸Salt Lake City, Utah, United States
Children's Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
University of Iowa/Holden Comprehensive Cancer Center
🇺🇸Iowa City, Iowa, United States
Norton Children's Hospital
🇺🇸Louisville, Kentucky, United States
C S Mott Children's Hospital
🇺🇸Ann Arbor, Michigan, United States
Floating Hospital for Children at Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Rainbow Babies and Childrens Hospital
🇺🇸Cleveland, Ohio, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, North Carolina, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Alberta Children's Hospital
🇨🇦Calgary, Alberta, Canada