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Trial record 1 of 1 for:    NCT01503515
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Caspofungin Acetate, Fluconazole, or Voriconazole in Preventing Fungal Infections in Patients Following Donor Stem Cell Transplant

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT01503515
First received: January 1, 2012
Last updated: January 18, 2017
Last verified: January 2017
  Purpose
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.

Condition Intervention Phase
Fungal Infection
Hematopoietic/Lymphoid Cancer
Drug: caspofungin acetate
Drug: fluconazole
Drug: voriconazole
Other: laboratory biomarker analysis
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Supportive Care
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)

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Development of proven or probable IFI defined according to criteria developed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group [ Time Frame: Up to 42 days following allogeneic HCT ]
    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.


Other Outcome Measures:
  • Development of proven or probable IFI [ Time Frame: Up to day 100 ]
    A log rank test will be performed comparing the incidence of proven/probable IFI between the 2 randomization arms.

  • Fungal-free-survival [ Time Frame: Time to death or proven/probable IFI during the first 42 and 100 days following allogeneic HCT ]
    Log rank test will be used to explore any treatment differences between the 2 arms on fungal-free survival.

  • Incidence of acute GVHD [ Time Frame: Up to 100 days after allogeneic HCT ]
    The binary incidence of acute GVHD and the percentage distribution of acute GVHD by stage and by overall clinical grade will be estimated for each arm and compared between the 2 arms by Chi-square test.


Enrollment: 292
Actual Study Start Date: March 2013
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (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.
Drug: caspofungin acetate
Given IV
Other Names:
  • Cancidas
  • L-743,873
  • MK-0991
Other: laboratory biomarker analysis
Optional correlative studies
Active Comparator: Arm II (fluconazole or 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.
Drug: fluconazole
Given IV or PO
Other Names:
  • Diflucan
  • FCZ
Drug: voriconazole
Given IV or PO
Other Names:
  • VCZ
  • Vfend
Other: laboratory biomarker analysis
Optional correlative studies

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.

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.

  Eligibility

Ages Eligible for Study:   3 Months to 20 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01503515

  Hide Study Locations
Locations
United States, Arizona
Phoenix Childrens Hospital
Phoenix, Arizona, United States, 85016
United States, California
Loma Linda University Medical Center
Loma Linda, California, United States, 92354
Children's Hospital and Research Center at Oakland
Oakland, California, United States, 94609-1809
Childrens Hospital of Orange County
Orange, California, United States, 92868-3874
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, United States, 94304
Rady Children's Hospital - San Diego
San Diego, California, United States, 92123
University of California San Francisco Medical Center-Parnassus
San Francisco, California, United States, 94143
United States, Delaware
Alfred I duPont Hospital for Children
Wilmington, Delaware, United States, 19803
United States, Florida
Nemours Children's Clinic - Jacksonville
Jacksonville, Florida, United States, 32207
All Children's Hospital
Saint Petersburg, Florida, United States, 33701
United States, Georgia
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, United States, 30322
United States, Indiana
Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
United States, Kentucky
Kosair Children's Hospital
Louisville, Kentucky, United States, 40202
United States, Louisiana
Children's Hospital-Main Campus
New Orleans, Louisiana, United States, 70118
United States, Massachusetts
Floating Hospital for Children at Tufts Medical Center
Boston, Massachusetts, United States, 02111
United States, Michigan
C S Mott Children's Hospital
Ann Arbor, Michigan, United States, 48109
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
Helen DeVos Children's Hospital at Spectrum Health
Grand Rapids, Michigan, United States, 49503
United States, Minnesota
University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota, United States, 55455
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216
United States, Missouri
The Childrens Mercy Hospital
Kansas City, Missouri, United States, 64108
United States, Nebraska
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, United States, 68114
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
Montefiore Medical Center - Moses Campus
Bronx, New York, United States, 10467-2490
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Children's Hospital Medical Center of Akron
Akron, Ohio, United States, 44308
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, United States, 44106
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Texas
Medical City Dallas Hospital
Dallas, Texas, United States, 75230
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States, 78229
United States, Utah
Primary Children's Hospital
Salt Lake City, Utah, United States, 84113
United States, Wisconsin
Midwest Children's Cancer Center
Milwaukee, Wisconsin, United States, 53226
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Principal Investigator: Christopher Dvorak, MD Children's Oncology Group
  More Information

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT01503515     History of Changes
Other Study ID Numbers: ACCL1131
NCI-2012-00102 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000721415 ( Other Identifier: ClinicalTrials.gov )
ACCL1131 ( Other Identifier: Children's Oncology Group )
COG-ACCL1131 ( Other Identifier: DCP )
ACCL1131 ( Other Identifier: CTEP )
U10CA095861 ( US NIH Grant/Contract Award Number )
Study First Received: January 1, 2012
Last Updated: January 18, 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Infection
Communicable Diseases
Mycoses
Caspofungin
Echinocandins
Fluconazole
Voriconazole
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 CYP3A Inhibitors

ClinicalTrials.gov processed this record on April 26, 2017