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CompletedNCT01503515Updated Oct 16, 2024Results posted

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

A Phase 3 interventional study of Caspofungin Acetate and Fluconazole in Fungal Infection and Hematopoietic and Lymphoid Cell Neoplasm, sponsored by Children's Oncology Group. Completed at 49 sites in 2 countries. Open to participants aged 3 Months to 20 Years. Per ClinicalTrials.gov, last updated 2024-10-16.

Sponsored by Children's Oncology Group · Phase 3, Interventional, and Supportive care

Phase
Phase 3
Study type
Interventional
Enrollment
292
Allocation
Randomized
Ages
3 Months to 20 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Fungal Infection
  • Hematopoietic and Lymphoid Cell Neoplasm
03

In context

Infections

6,688 studies on the registry are indexed under Infections; 807 are open to participants now.

This study's enrollment of 292 is above the median of 120 across 4,201 interventional studies indexed under Infections.

Browse Infections studies →

Lead sponsor

Children's Oncology Group is the lead sponsor of 436 studies on the registry; 34 are open to participants now.

Of its 12 completed or terminated interventional studies of FDA-regulated products, 11 (92%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
3 Months to 20 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Phase 3
Primary purpose
Supportive care
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
292 participants (actual)

Study arms

  • 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 · Other: Laboratory Biomarker Analysis

  • 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 · Other: Laboratory Biomarker Analysis · Drug: Voriconazole

Interventions

  • DrugCaspofungin Acetate

    Given IV

    Also known as: Cancidas

  • DrugFluconazole

    Given IV or PO

    Also known as: Diflucan

  • OtherLaboratory Biomarker Analysis

    Optional correlative studies

  • DrugVoriconazole

    Given IV or PO

    Also known as: Vfend

06

What researchers measure

Primary outcomes

  1. 42-day-cumulative Incidence of Proven or Probable Invasive Fungal Infections (IFI)

    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).

    Time frame: Up to 42 days following allogeneic HCT

Other outcomes

  1. 100-day-cumulative Incidence of Proven or Probable IFI

    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).

    Time frame: Up to day 100 following allogeneic HCT

  2. Fungal-free-survival

    Defined as time to death or proven/probable IFI during the first 42 days following allogeneic HCT.

    Time frame: Up to 42 days following allogeneic HCT

  3. Incidence of Overall Clinical GVHD Grades III and IV

    The percentage distribution of overall clinical grades III and IV will be estimated for each arm.

    Time frame: Up to 100 days after allogeneic HCT

  4. Incidence of Overall Clinical GVHD Grades II to IV

    The percentage distribution of overall clinical grades II and IV will be estimated for each arm.

    Time frame: Up to 100 days after allogeneic HCT

  5. Fungal-free-survival

    Defined as time to death or proven/probable IFI during the first 100 days following allogeneic HCT.

    Time frame: Up to 100 days following allogeneic HCT

  6. Sensitivity of Beta-D Glucan Assay for the Diagnosis of IFI Using Fungitell Assay

    Sensitivity of the beta-D glucan assay will be determined using standard formulas and EORTC/MSG criteria as the gold standard.

    Time frame: Up to day 42 following allogeneic HCT

  7. Specificity of Beta-D Glucan Assay for the Diagnosis of IFI Using Fungitell Assay

    Specificity of the beta-D glucan assay will be determined using standard formulas and EORTC/MSG criteria as the gold standard.

    Time frame: Up to day 42 following allogeneic HCT

  8. Positive Predictive Value of Beta-D Glucan Assay for the Diagnosis of IFI Using Fungitell Assay

    Positive predictive value of the beta-D glucan assay will be determined using standard formulas and EORTC/MSG criteria as the gold standard.

    Time frame: Up to day 42 following allogeneic HCT

  9. Negative Predictive Value of Beta-D Glucan Assay for the Diagnosis of IFI Using Fungitell Assay

    Negative predictive value of the beta-D glucan assay will be determined using standard formulas and EORTC/MSG criteria as the gold standard.

    Time frame: Up to day 42 following allogeneic HCT

07

Results

Posted Jan 7, 2021

Participant flow

Participant flow — Overall Study
MilestoneArm I (Caspofungin Acetate)Arm II (Fluconazole or Voriconazole)
Started145147
Completed124112
Not completed2135
Withdrew: Adverse event45
Withdrew: Death01
Withdrew: Physician decision1423
Withdrew: Withdrawal by subject01
Withdrew: Institutional dx of proven/probable ifi24
Withdrew: Ineligible11

Outcome measures

Primary42-day-cumulative Incidence of Proven or Probable Invasive Fungal Infections (IFI)

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).

Time frame:
Up to 42 days following allogeneic HCT
Reported as:
Number · percentage of patients
42-day-cumulative Incidence of Proven or Probable Invasive Fungal Infections (IFI)
percentage of patientsArm I (Caspofungin Acetate)Arm II (Fluconazole or Voriconazole)
42-day-cumulative Incidence of Proven or Probable Invasive Fungal Infections (IFI)1.4 (0.3 to 5.4)1.4 (0.4 to 5.5)
Other pre-specified100-day-cumulative Incidence of Proven or Probable IFI

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).

Time frame:
Up to day 100 following allogeneic HCT

Results for this outcome have not been posted.

Other pre-specifiedFungal-free-survival

Defined as time to death or proven/probable IFI during the first 42 days following allogeneic HCT.

Time frame:
Up to 42 days following allogeneic HCT

Results for this outcome have not been posted.

Other pre-specifiedIncidence of Overall Clinical GVHD Grades III and IV

The percentage distribution of overall clinical grades III and IV will be estimated for each arm.

Time frame:
Up to 100 days after allogeneic HCT

Results for this outcome have not been posted.

Other pre-specifiedIncidence of Overall Clinical GVHD Grades II to IV

The percentage distribution of overall clinical grades II and IV will be estimated for each arm.

Time frame:
Up to 100 days after allogeneic HCT

Results for this outcome have not been posted.

Other pre-specifiedFungal-free-survival

Defined as time to death or proven/probable IFI during the first 100 days following allogeneic HCT.

Time frame:
Up to 100 days following allogeneic HCT

Results for this outcome have not been posted.

Other pre-specifiedSensitivity of Beta-D Glucan Assay for the Diagnosis of IFI Using Fungitell Assay

Sensitivity of the beta-D glucan assay will be determined using standard formulas and EORTC/MSG criteria as the gold standard.

Time frame:
Up to day 42 following allogeneic HCT

Results for this outcome have not been posted.

Other pre-specifiedSpecificity of Beta-D Glucan Assay for the Diagnosis of IFI Using Fungitell Assay

Specificity of the beta-D glucan assay will be determined using standard formulas and EORTC/MSG criteria as the gold standard.

Time frame:
Up to day 42 following allogeneic HCT

Results for this outcome have not been posted.

Other pre-specifiedPositive Predictive Value of Beta-D Glucan Assay for the Diagnosis of IFI Using Fungitell Assay

Positive predictive value of the beta-D glucan assay will be determined using standard formulas and EORTC/MSG criteria as the gold standard.

Time frame:
Up to day 42 following allogeneic HCT

Results for this outcome have not been posted.

Other pre-specifiedNegative Predictive Value of Beta-D Glucan Assay for the Diagnosis of IFI Using Fungitell Assay

Negative predictive value of the beta-D glucan assay will be determined using standard formulas and EORTC/MSG criteria as the gold standard.

Time frame:
Up to day 42 following allogeneic HCT

Results for this outcome have not been posted.

Adverse events

Collected over Collected Adverse Events within the 100 day observation period. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Arm I (Caspofungin Acetate)9/144 (6.3%)4/144 (2.8%)29/144 (20.1%)
Arm II (Fluconazole or Voriconazole)10/146 (6.8%)3/146 (2.1%)30/146 (20.5%)
Most frequent serious events
Most frequent serious events
EventArm I (Caspofungin Acetate)Arm II (Fluconazole or Voriconazole)
Infections and infestations - Other, specifyInfections and infestations1/1440/146
Multi-organ failureGeneral disorders1/1440/146
Respiratory failureRespiratory, thoracic and mediastinal disorders1/1440/146
SepsisInfections and infestations1/1441/146
Adult respiratory distress syndromeRespiratory, thoracic and mediastinal disorders0/1441/146
Death NOSGeneral disorders0/1441/146
Most frequent other events
Showing 10 of 47
Most frequent other events
EventArm I (Caspofungin Acetate)Arm II (Fluconazole or Voriconazole)
Respiratory failureRespiratory, thoracic and mediastinal disorders7/1447/146
Alanine aminotransferase increasedInvestigations5/1445/146
Aspartate aminotransferase increasedInvestigations3/1445/146
Acute kidney injuryRenal and urinary disorders4/1441/146
GGT increasedInvestigations4/1440/146
Blood bilirubin increasedInvestigations3/1440/146
HypokalemiaMetabolism and nutrition disorders3/1441/146
SepsisInfections and infestations3/1442/146
Mucositis oralGastrointestinal disorders2/1441/146
HypercalcemiaMetabolism and nutrition disorders0/1442/146

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Arm I (Caspofungin Acetate)Arm II (Fluconazole or Voriconazole)Total
<=18 years134133267
Between 18 and 65 years111425
>=65 years000
Age, Continuous
Age, Continuous(years)Arm I (Caspofungin Acetate)Arm II (Fluconazole or Voriconazole)Total
Mean9.2 ± 5.79.1 ± 6.09.2 ± 5.8
Sex: Female, Male
Sex: Female, Male(Participants)Arm I (Caspofungin Acetate)Arm II (Fluconazole or Voriconazole)Total
Female5656112
Male8991180
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Arm I (Caspofungin Acetate)Arm II (Fluconazole or Voriconazole)Total
Hispanic or Latino262753
Not Hispanic or Latino113107220
Unknown or Not Reported61319
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Arm I (Caspofungin Acetate)Arm II (Fluconazole or Voriconazole)Total
American Indian or Alaska Native123
Asian9615
Native Hawaiian or Other Pacific Islander101
Black or African American112233
White11097207
More than one race202
Unknown or Not Reported112031
Region of Enrollment
Region of Enrollment(participants)Arm I (Caspofungin Acetate)Arm II (Fluconazole or Voriconazole)Total
United States136132268
Canada91524
08

Study locations

49 sites
  • Phoenix Childrens Hospital
    Phoenix, Arizona 85016, United States
  • Loma Linda University Medical Center
    Loma Linda, California 92354, United States
  • Children's Hospital and Research Center at Oakland
    Oakland, California 94609-1809, United States
  • Children's Hospital of Orange County
    Orange, California 92868, United States
  • Lucile Packard Children's Hospital Stanford University
    Palo Alto, California 94304, United States
  • Rady Children's Hospital - San Diego
    San Diego, California 92123, United States
  • UCSF Medical Center-Parnassus
    San Francisco, California 94143, United States
  • UCSF Medical Center-Mission Bay
    San Francisco, California 94158, United States
  • Alfred I duPont Hospital for Children
    Wilmington, Delaware 19803, United States
  • Nemours Children's Clinic-Jacksonville
    Jacksonville, Florida 32207, United States
  • Johns Hopkins All Children's Hospital
    Saint Petersburg, Florida 33701, United States
  • Children's Healthcare of Atlanta - Egleston
    Atlanta, Georgia 30322, United States
  • University of Hawaii Cancer Center
    Honolulu, Hawaii 96813, United States
  • Kapiolani Medical Center for Women and Children
    Honolulu, Hawaii 96826, United States
  • Riley Hospital for Children
    Indianapolis, Indiana 46202, United States
  • University of Iowa/Holden Comprehensive Cancer Center
    Iowa City, Iowa 52242, United States
  • Norton Children's Hospital
    Louisville, Kentucky 40202, United States
  • Children's Hospital New Orleans
    New Orleans, Louisiana 70118, United States
  • Floating Hospital for Children at Tufts Medical Center
    Boston, Massachusetts 02111, United States
  • C S Mott Children's Hospital
    Ann Arbor, Michigan 48109, United States
  • Wayne State University/Karmanos Cancer Institute
    Detroit, Michigan 48201, United States
  • Helen DeVos Children's Hospital at Spectrum Health
    Grand Rapids, Michigan 49503, United States
  • University of Minnesota/Masonic Cancer Center
    Minneapolis, Minnesota 55455, United States
  • Mayo Clinic in Rochester
    Rochester, Minnesota 55905, United States
  • University of Mississippi Medical Center
    Jackson, Mississippi 39216, United States
  • Children's Mercy Hospitals and Clinics
    Kansas City, Missouri 64108, United States
  • Children's Hospital and Medical Center of Omaha
    Omaha, Nebraska 68114, United States
  • University of Nebraska Medical Center
    Omaha, Nebraska 68198, United States
  • Hackensack University Medical Center
    Hackensack, New Jersey 07601, United States
  • Montefiore Medical Center - Moses Campus
    Bronx, New York 10467, United States
  • Roswell Park Cancer Institute
    Buffalo, New York 14263, United States
  • UNC Lineberger Comprehensive Cancer Center
    Chapel Hill, North Carolina 27599, United States
  • Duke University Medical Center
    Durham, North Carolina 27710, United States
  • Children's Hospital Medical Center of Akron
    Akron, Ohio 44308, United States
  • Rainbow Babies and Childrens Hospital
    Cleveland, Ohio 44106, United States
  • Cleveland Clinic Foundation
    Cleveland, Ohio 44195, United States
  • Nationwide Children's Hospital
    Columbus, Ohio 43205, United States
  • University of Oklahoma Health Sciences Center
    Oklahoma City, Oklahoma 73104, United States
  • Children's Hospital of Philadelphia
    Philadelphia, Pennsylvania 19104, United States
  • Children's Hospital of Pittsburgh of UPMC
    Pittsburgh, Pennsylvania 15224, United States
  • Vanderbilt University/Ingram Cancer Center
    Nashville, Tennessee 37232, United States
  • Medical City Dallas Hospital
    Dallas, Texas 75230, United States
  • UT Southwestern/Simmons Cancer Center-Dallas
    Dallas, Texas 75390, United States
  • Methodist Children's Hospital of South Texas
    San Antonio, Texas 78229, United States
  • Primary Children's Hospital
    Salt Lake City, Utah 84113, United States
  • Children's Hospital of Wisconsin
    Milwaukee, Wisconsin 53226, United States
  • Alberta Children's Hospital
    Calgary, Alberta T3B 6A8, Canada
  • CancerCare Manitoba
    Winnipeg, Manitoba R3E 0V9, Canada
  • Hospital for Sick Children
    Toronto, Ontario M5G 1X8, Canada
09

References and documents

Publications

  • Dvorak CC, Fisher BT, Esbenshade AJ, Nieder ML, Alexander S, Steinbach WJ, Dang H, Villaluna D, Chen L, Skeens M, Zaoutis TE, Sung L. A Randomized Trial of Caspofungin vs Triazoles Prophylaxis for Invasive Fungal Disease in Pediatric Allogeneic Hematopoietic Cell Transplant. J Pediatric Infect Dis Soc. 2021 Apr 30;10(4):417-425. doi: 10.1093/jpids/piaa119. PubMed 33136159 ↗

Study documents

  • Protocol, analysis plan and consent form · Nov 16, 2015

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 16, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01503515
Lead sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Jan 4, 2012
Start date
Mar 21, 2013
Primary completion
Dec 31, 2019
Completion
Sep 30, 2021
Results posted
Jan 7, 2021
Last update
Oct 16, 2024

Study contacts

Christopher C Dvorak
principal investigator · Children's Oncology Group

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
View the source record on ClinicalTrials.gov ↗

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