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 currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Children's Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT01503515
First received: January 1, 2012
Last updated: August 5, 2014
Last verified: August 2014
  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
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Development of proven or probable IFI [ Time Frame: Up to day 100 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 590
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
Genders Eligible for Study:   Both
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

  Show 43 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Christopher Dvorak Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT01503515     History of Changes
Other Study ID Numbers: ACCL1131, NCI-2012-00102, CDR0000721415, ACCL1131, COG-ACCL1131, ACCL1131, U10CA095861
Study First Received: January 1, 2012
Last Updated: August 5, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Communicable Diseases
Infection
Mycoses
Caspofungin
Echinocandins
Fluconazole
Voriconazole
14-alpha Demethylase Inhibitors
Anti-Infective Agents
Antifungal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014