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

NCT ID: NCT01503515

Last Updated: 2024-10-16

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

292 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-03-21

Study Completion Date

2021-09-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Fungal Infection Hematopoietic and Lymphoid Cell Neoplasm

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Caspofungin Acetate

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Optional correlative studies

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.

Group Type ACTIVE_COMPARATOR

Fluconazole

Intervention Type DRUG

Given IV or PO

Laboratory Biomarker Analysis

Intervention Type OTHER

Optional correlative studies

Voriconazole

Intervention Type DRUG

Given IV or PO

Interventions

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Caspofungin Acetate

Given IV

Intervention Type DRUG

Fluconazole

Given IV or PO

Intervention Type DRUG

Laboratory Biomarker Analysis

Optional correlative studies

Intervention Type OTHER

Voriconazole

Given IV or PO

Intervention Type DRUG

Other Intervention Names

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Cancidas Diflucan Vfend

Eligibility Criteria

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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
Minimum Eligible Age

3 Months

Maximum Eligible Age

20 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Christopher C Dvorak

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

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Phoenix Childrens Hospital

Phoenix, Arizona, United States

Site Status

Loma Linda University Medical Center

Loma Linda, California, United States

Site Status

Children's Hospital and Research Center at Oakland

Oakland, California, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, United States

Site Status

Rady Children's Hospital - San Diego

San Diego, California, United States

Site Status

UCSF Medical Center-Parnassus

San Francisco, California, United States

Site Status

UCSF Medical Center-Mission Bay

San Francisco, California, United States

Site Status

Alfred I duPont Hospital for Children

Wilmington, Delaware, United States

Site Status

Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, United States

Site Status

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, United States

Site Status

Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, United States

Site Status

University of Hawaii Cancer Center

Honolulu, Hawaii, United States

Site Status

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, United States

Site Status

Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

Site Status

Norton Children's Hospital

Louisville, Kentucky, United States

Site Status

Children's Hospital New Orleans

New Orleans, Louisiana, United States

Site Status

Floating Hospital for Children at Tufts Medical Center

Boston, Massachusetts, United States

Site Status

C S Mott Children's Hospital

Ann Arbor, Michigan, United States

Site Status

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Helen DeVos Children's Hospital at Spectrum Health

Grand Rapids, Michigan, United States

Site Status

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, United States

Site Status

Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Montefiore Medical Center - Moses Campus

The Bronx, New York, United States

Site Status

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Children's Hospital Medical Center of Akron

Akron, Ohio, United States

Site Status

Rainbow Babies and Childrens Hospital

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Medical City Dallas Hospital

Dallas, Texas, United States

Site Status

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

Site Status

Methodist Children's Hospital of South Texas

San Antonio, Texas, United States

Site Status

Primary Children's Hospital

Salt Lake City, Utah, United States

Site Status

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Alberta Children's Hospital

Calgary, Alberta, Canada

Site Status

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Countries

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United States Canada

References

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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.

Reference Type DERIVED
PMID: 33136159 (View on PubMed)

Provided Documents

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Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Study Documents

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Document Type: Individual Participant Data Set

Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive

View Document

Other Identifiers

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NCI-2012-00102

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000721415

Identifier Type: -

Identifier Source: secondary_id

ACCL1131

Identifier Type: OTHER

Identifier Source: secondary_id

COG-ACCL1131

Identifier Type: OTHER

Identifier Source: secondary_id

ACCL1131

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA095861

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UG1CA189955

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ACCL1131

Identifier Type: -

Identifier Source: org_study_id

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