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

October 4, 2024 updated by: Children's Oncology Group

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)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
292

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T3B 6A8
        • Alberta Children's Hospital
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3E 0V9
        • CancerCare Manitoba
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Hospital for Sick Children
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85016
        • Phoenix Childrens Hospital
    • California
      • Loma Linda, California, United States, 92354
        • Loma Linda University Medical Center
      • Oakland, California, United States, 94609-1809
        • Children's Hospital and Research Center at Oakland
      • Orange, California, United States, 92868
        • Children's Hospital of Orange County
      • Palo Alto, California, United States, 94304
        • Lucile Packard Children's Hospital Stanford University
      • San Diego, California, United States, 92123
        • Rady Children's Hospital - San Diego
      • San Francisco, California, United States, 94158
        • UCSF Medical Center-Mission Bay
      • San Francisco, California, United States, 94143
        • UCSF Medical Center-Parnassus
    • Delaware
      • Wilmington, Delaware, United States, 19803
        • Alfred I duPont Hospital for Children
    • Florida
      • Jacksonville, Florida, United States, 32207
        • Nemours Children's Clinic-Jacksonville
      • Saint Petersburg, Florida, United States, 33701
        • Johns Hopkins All Children's Hospital
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Children's Healthcare of Atlanta - Egleston
    • Hawaii
      • Honolulu, Hawaii, United States, 96813
        • University of Hawaii Cancer Center
      • Honolulu, Hawaii, United States, 96826
        • Kapiolani Medical Center for Women and Children
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Riley Hospital for Children
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa/Holden Comprehensive Cancer Center
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Norton Children's Hospital
    • Louisiana
      • New Orleans, Louisiana, United States, 70118
        • Children's Hospital New Orleans
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • Floating Hospital for Children at Tufts Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • C S Mott Children's Hospital
      • Detroit, Michigan, United States, 48201
        • Wayne State University/Karmanos Cancer Institute
      • Grand Rapids, Michigan, United States, 49503
        • Helen DeVos Children's Hospital at Spectrum Health
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota/Masonic Cancer Center
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Children's Mercy Hospitals and Clinics
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center
      • Omaha, Nebraska, United States, 68114
        • Children's Hospital and Medical Center of Omaha
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
    • New York
      • Bronx, New York, United States, 10467
        • Montefiore Medical Center - Moses Campus
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • UNC Lineberger Comprehensive Cancer Center
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Ohio
      • Akron, Ohio, United States, 44308
        • Children's Hospital Medical Center of Akron
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
      • Cleveland, Ohio, United States, 44106
        • Rainbow Babies and Childrens Hospital
      • Columbus, Ohio, United States, 43205
        • Nationwide Children's Hospital
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
      • Pittsburgh, Pennsylvania, United States, 15224
        • Children's Hospital of Pittsburgh of UPMC
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University/Ingram Cancer Center
    • Texas
      • Dallas, Texas, United States, 75390
        • UT Southwestern/Simmons Cancer Center-Dallas
      • Dallas, Texas, United States, 75230
        • Medical City Dallas Hospital
      • San Antonio, Texas, United States, 78229
        • Methodist Children's Hospital of South Texas
    • Utah
      • Salt Lake City, Utah, United States, 84113
        • Primary Children's Hospital
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Children's Hospital of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

3 months to 20 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.
Other: Laboratory Biomarker Analysis
Optional correlative studies
Drug: Caspofungin Acetate
Given IV
Other Names:
  • Cancidas
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.
Other: Laboratory Biomarker Analysis
Optional correlative studies
Drug: Fluconazole
Given IV or PO
Other Names:
  • Diflucan
Drug: Voriconazole
Given IV or PO
Other Names:
  • Vfend

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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).
Up to 42 days following allogeneic HCT

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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).
Up to day 100 following allogeneic HCT
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.
Up to 42 days following allogeneic HCT
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.
Up to 100 days after allogeneic HCT
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.
Up to 100 days after allogeneic HCT
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.
Up to 100 days following allogeneic HCT
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.
Up to day 42 following allogeneic HCT
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.
Up to day 42 following allogeneic HCT
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.
Up to day 42 following allogeneic HCT
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.
Up to day 42 following allogeneic HCT

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Children's Oncology Group

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Christopher C Dvorak, Children's Oncology Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 21, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 30, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 1, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 1, 2012

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 4, 2012

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 16, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 4, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ACCL1131 (Other Identifier: CTEP)
  • U10CA095861 (U.S. NIH Grant/Contract)
  • UG1CA189955 (U.S. NIH Grant/Contract)
  • NCI-2012-00102 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • CDR0000721415
  • COG-ACCL1131 (Other Identifier: DCP)

Plan for Individual participant data (IPD)

Study Data/Documents

  1. Individual Participant Data Set
    Information comments: Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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