Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01503515
Recruitment Status : Active, not recruiting
First Posted : January 4, 2012
Last Update Posted : August 26, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Fungal Infection Hematopoietic and Lymphoid Cell Neoplasm Drug: Caspofungin Acetate Drug: Fluconazole Other: Laboratory Biomarker Analysis Drug: Voriconazole Phase 3

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 292 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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)
Actual Study Start Date : March 21, 2013
Actual Primary Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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 Name: Cancidas

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 Name: Diflucan

Other: Laboratory Biomarker Analysis
Optional correlative studies

Drug: Voriconazole
Given IV or PO
Other Name: Vfend




Primary Outcome Measures :
  1. 42-day-cumulative incidence of proven or probable invasive fungal infections (IFI) [ Time Frame: 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).


Other Outcome Measures:
  1. 100-day-cumulative incidence of proven or probable IFI [ Time Frame: Up to day 100 following allogeneic HCT ]
    Kaplan-Meier curves will be used to estimate the 100- 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).

  2. Fungal-free-survival [ Time Frame: Up to 42 days following allogeneic HCT ]
    Defined as time to death or proven/probable IFI during the first 42 days following allogeneic HCT.

  3. Incidence of overall clinical GVHD grades III and IV [ Time Frame: Up to 100 days after allogeneic HCT ]
    The percentage distribution of overall clinical grades III and IV will be estimated for each arm.

  4. Incidence of overall clinical GVHD grades II to IV [ Time Frame: Up to 100 days after allogeneic HCT ]
    The percentage distribution of overall clinical grades II and IV will be estimated for each arm.

  5. Fungal-free-survival [ Time Frame: Up to 100 days following allogeneic HCT ]
    Defined as time to death or proven/probable IFI during the first 100 days following allogeneic HCT.

  6. Sensitivity of beta-D glucan assay for the diagnosis of IFI using Fungitell assay [ Time Frame: Up to day 42 following allogeneic HCT ]
    Sensitivity of the beta-D glucan assay will be determined using standard formulas and EORTC/MSG criteria as the gold standard.

  7. Specificity of beta-D glucan assay for the diagnosis of IFI using Fungitell assay [ Time Frame: Up to day 42 following allogeneic HCT ]
    Specificity of the beta-D glucan assay will be determined using standard formulas and EORTC/MSG criteria as the gold standard.

  8. Positive predictive value of beta-D glucan assay for the diagnosis of IFI using Fungitell assay [ Time Frame: Up to day 42 following allogeneic HCT ]
    Positive predictive value of the beta-D glucan assay will be determined using standard formulas and EORTC/MSG criteria as the gold standard.

  9. Negative predictive value of beta-D glucan assay for the diagnosis of IFI using Fungitell assay [ Time Frame: Up to day 42 following allogeneic HCT ]
    Negative predictive value of the beta-D glucan assay will be determined using standard formulas and EORTC/MSG criteria as the gold standard.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01503515


Locations
Show Show 49 study locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Christopher C Dvorak Children's Oncology Group
Layout table for additonal information
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT01503515    
Other Study ID Numbers: ACCL1131
NCI-2012-00102 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000721415
ACCL1131 ( Other Identifier: Children's Oncology Group )
COG-ACCL1131 ( Other Identifier: DCP )
ACCL1131 ( Other Identifier: CTEP )
U10CA095861 ( U.S. NIH Grant/Contract )
UG1CA189955 ( U.S. NIH Grant/Contract )
First Posted: January 4, 2012    Key Record Dates
Last Update Posted: August 26, 2020
Last Verified: January 2020
Additional relevant MeSH terms:
Layout table for MeSH terms
Infection
Communicable Diseases
Mycoses
Fluconazole
Voriconazole
Caspofungin
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