NCT01307579

Brief Summary

This randomized phase III trial compares the effectiveness of caspofungin to fluconazole in preventing invasive fungal infections in patients receiving chemotherapy for acute myeloid leukemia (AML). Antifungal prophylaxis is considered standard of care in children and adults with prolonged neutropenia after chemotherapy for AML however the ideal antifungal agent for prophylaxis in children is not known. Caspofungin has activity against yeast and some molds while fluconazole coverage is limited to just yeasts. Adult randomized trials suggest that agents with activity against yeasts and molds are more effective than those with just activity against yeasts. There are limited data to answer this comparative question in children. This study will establish much needed pediatric data to guide clinical decision making on optimal antifungal prophylaxis.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
517

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Apr 2011

Longer than P75 for phase_3

Geographic Reach
3 countries

179 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 1, 2011

Completed
2 days until next milestone

First Posted

Study publicly available on registry

March 3, 2011

Completed
1 month until next milestone

Study Start

First participant enrolled

April 4, 2011

Completed
7.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2018

Completed
1.2 years until next milestone

Results Posted

Study results publicly available

September 17, 2019

Completed
10 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2020

Completed
Last Updated

March 30, 2021

Status Verified

June 1, 2019

Enrollment Period

7.2 years

First QC Date

March 1, 2011

Results QC Date

June 11, 2019

Last Update Submit

March 26, 2021

Conditions

Keywords

Pediatricsleukemiainvasive fungal infection

Outcome Measures

Primary Outcomes (1)

  • Percentage of Participants With Proven or Probable Invasive Fungal Infections (IFI)

    Proven or probable IFI is defined according to criteria developed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG).

    Up to 5 months since enrollment

Secondary Outcomes (3)

  • Percentage of Participants With Proven or Probable Invasive Aspergillosis (IA)

    Up to 5 months since enrollment

  • Overall Survival

    Up to 2 years post enrollment

  • Percentage of Participants That Need Empiric Antifungal Therapy

    Up to 5 months since enrollment

Other Outcomes (5)

  • Sensitivity of Galactomannan and Beta-D Glucan Assays for the Diagnosis of Proven or Probable IFI

    Up to 5 months since enrollment

  • Specificity of Galactomannan and Beta-D Glucan Assays for the Diagnosis of Proven or Probable IFI

    Up to 5 months since enrollment

  • Positive Predictive Value of Galactomannan and Beta-D Glucan Assays for the Diagnosis of Proven or Probable IFI

    Up to 5 months since enrollment

  • +2 more other outcomes

Study Arms (2)

Arm I (caspofungin acetate)

EXPERIMENTAL

Patients receive caspofungin acetate IV over one hour QD beginning within 24-72 hours following the last dose of chemotherapy for each course. and continuing until ANC \> 100-500/uL following the nadir or the next chemotherapy course begins.

Drug: Caspofungin AcetateOther: Laboratory Biomarker Analysis

Arm II (fluconazole)

ACTIVE COMPARATOR

Patients receive fluconazole IV over 1-2 hours or PO QD beginning within 24-72 hours following the last dose of chemotherapy for each course.

Drug: FluconazoleOther: Laboratory Biomarker Analysis

Interventions

Given IV

Also known as: Cancidas
Arm I (caspofungin acetate)

Given IV or PO

Also known as: Diflucan
Arm II (fluconazole)

Correlative studies

Arm I (caspofungin acetate)Arm II (fluconazole)

Eligibility Criteria

Age3 Months - 30 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Patients must have one of the following diagnoses and/or treatment plans:
  • Newly diagnosed de novo AML
  • First or subsequent relapse of AML
  • Secondary AML
  • Treatment with institutional standard AML therapy in those without AML (for example, myelodysplastic syndrome, bone marrow blasts \> 5% or biphenotypia)
  • Note: Patients with a history of prolonged antifungal therapy (example, relapsed AML) are eligible
  • 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 (age 1 month to \< 6 months)
  • =\< 0.5 mg/dL (age 6 months to \< 1 year)
  • =\< 0.6 mg/dL (age 1 to \< 2 years)
  • =\< 0.8 mg/dL (age 2 to \< 6 years)
  • =\< 1 mg/dL (age 6 to \< 10 years)
  • =\< 1.2 mg/dL (age 10 to \< 13 years)
  • =\< 1.4 mg/dL (females age \>= 13 years)
  • =\< 1.5 mg/dL (males age 13 to \< 16 years)
  • +3 more criteria

You may not qualify if:

  • Patients with the following diagnoses are not eligible:
  • Acute promyelocytic leukemia (APL)
  • Down syndrome
  • Juvenile myelomonocytic leukemia (JMML)
  • Patients with a documented history of invasive fungal infection (IFI) within the previous 30 days are not eligible
  • Patients with a history of echinocandin or fluconazole hypersensitivity are not eligible
  • Patients receiving treatment for an IFI are not eligible
  • Female patients of childbearing age must have a negative pregnancy test
  • Patients must agree to use an effective birth control method
  • Lactating patients must agree not to nurse a child while on this trial

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (179)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

Phoenix Childrens Hospital

Phoenix, Arizona, 85016, United States

Location

Arkansas Children's Hospital

Little Rock, Arkansas, 72202-3591, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Kaiser Permanente Downey Medical Center

Downey, California, 90242, United States

Location

Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

Miller Children's and Women's Hospital Long Beach

Long Beach, California, 90806, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Valley Children's Hospital

Madera, California, 93636, United States

Location

Kaiser Permanente-Oakland

Oakland, California, 94611, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Rady Children's Hospital - San Diego

San Diego, California, 92123, United States

Location

UCSF Medical Center-Parnassus

San Francisco, California, 94143, United States

Location

UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

Location

Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

Denver, Colorado, 80218, United States

Location

Connecticut Children's Medical Center

Hartford, Connecticut, 06106, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Alfred I duPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Broward Health Medical Center

Fort Lauderdale, Florida, 33316, United States

Location

Lee Memorial Health System

Fort Myers, Florida, 33901, United States

Location

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, 33908, United States

Location

University of Florida Health Science Center - Gainesville

Gainesville, Florida, 32610, United States

Location

Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Hollywood, Florida, 33021, United States

Location

Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, 32207, United States

Location

Florida Hospital Orlando

Orlando, Florida, 32803, United States

Location

Nemours Children's Clinic - Orlando

Orlando, Florida, 32806, United States

Location

UF Cancer Center at Orlando Health

Orlando, Florida, 32806, United States

Location

Nemours Children's Hospital

Orlando, Florida, 32827, United States

Location

Nemours Children's Clinic - Pensacola

Pensacola, Florida, 32504, United States

Location

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Tampa General Hospital

Tampa, Florida, 33606, United States

Location

Saint Joseph's Hospital/Children's Hospital-Tampa

Tampa, Florida, 33607, United States

Location

Saint Mary's Hospital

West Palm Beach, Florida, 33407, United States

Location

Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, 30322, United States

Location

Memorial Health University Medical Center

Savannah, Georgia, 31404, United States

Location

University of Hawaii Cancer Center

Honolulu, Hawaii, 96813, United States

Location

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, 96826, United States

Location

Saint Luke's Mountain States Tumor Institute

Boise, Idaho, 83712, United States

Location

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611, United States

Location

University of Illinois

Chicago, Illinois, 60612, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Advocate Children's Hospital-Oak Lawn

Oak Lawn, Illinois, 60453, United States

Location

Southern Illinois University School of Medicine

Springfield, Illinois, 62702, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Saint Vincent Hospital and Health Care Center

Indianapolis, Indiana, 46260, United States

Location

Blank Children's Hospital

Des Moines, Iowa, 50309, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

Norton Children's Hospital

Louisville, Kentucky, 40202, United States

Location

Tulane University Health Sciences Center

New Orleans, Louisiana, 70112, United States

Location

Children's Hospital New Orleans

New Orleans, Louisiana, 70118, United States

Location

Ochsner Medical Center Jefferson

New Orleans, Louisiana, 70121, United States

Location

Eastern Maine Medical Center

Bangor, Maine, 04401, United States

Location

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Sinai Hospital of Baltimore

Baltimore, Maryland, 21215, United States

Location

Walter Reed National Military Medical Center

Bethesda, Maryland, 20889-5600, United States

Location

Floating Hospital for Children at Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Ascension Saint John Hospital

Detroit, Michigan, 48236, United States

Location

Michigan State University Clinical Center

East Lansing, Michigan, 48824-7016, United States

Location

Hurley Medical Center

Flint, Michigan, 48503, United States

Location

Helen DeVos Children's Hospital at Spectrum Health

Grand Rapids, Michigan, 49503, United States

Location

Bronson Methodist Hospital

Kalamazoo, Michigan, 49007, United States

Location

Kalamazoo Center for Medical Studies

Kalamazoo, Michigan, 49008, United States

Location

Beaumont Children's Hospital-Royal Oak

Royal Oak, Michigan, 48073, United States

Location

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, 55404, United States

Location

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Columbia Regional

Columbia, Missouri, 65201, United States

Location

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, 64108, United States

Location

Cardinal Glennon Children's Medical Center

St Louis, Missouri, 63104, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Mercy Hospital Saint Louis

St Louis, Missouri, 63141, United States

Location

Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, 68114, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

University Medical Center of Southern Nevada

Las Vegas, Nevada, 89102, United States

Location

Nevada Cancer Research Foundation CCOP

Las Vegas, Nevada, 89106, United States

Location

Sunrise Hospital and Medical Center

Las Vegas, Nevada, 89109, United States

Location

Alliance for Childhood Diseases/Cure 4 the Kids Foundation

Las Vegas, Nevada, 89135, United States

Location

Summerlin Hospital Medical Center

Las Vegas, Nevada, 89144, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Saint Barnabas Medical Center

Livingston, New Jersey, 07039, United States

Location

Morristown Medical Center

Morristown, New Jersey, 07960, United States

Location

Saint Peter's University Hospital

New Brunswick, New Jersey, 08901, United States

Location

Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

New Brunswick, New Jersey, 08903, United States

Location

Newark Beth Israel Medical Center

Newark, New Jersey, 07112, United States

Location

Saint Joseph's Regional Medical Center

Paterson, New Jersey, 07503, United States

Location

Overlook Hospital

Summit, New Jersey, 07902, United States

Location

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87102, United States

Location

Albany Medical Center

Albany, New York, 12208, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

NYU Winthrop Hospital

Mineola, New York, 11501, United States

Location

The Steven and Alexandra Cohen Children's Medical Center of New York

New Hyde Park, New York, 11040, United States

Location

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

Location

Columbia University/Herbert Irving Cancer Center

New York, New York, 10032, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Stony Brook University Medical Center

Stony Brook, New York, 11794, United States

Location

State University of New York Upstate Medical University

Syracuse, New York, 13210, United States

Location

Montefiore Medical Center - Moses Campus

The Bronx, New York, 10467, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

Mission Hospital Inc-Memorial Campus

Asheville, North Carolina, 28801, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, 28203, United States

Location

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, 28204, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

East Carolina University

Greenville, North Carolina, 27834, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Sanford Broadway Medical Center

Fargo, North Dakota, 58122, United States

Location

Children's Hospital Medical Center of Akron

Akron, Ohio, 44308, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Rainbow Babies and Childrens Hospital

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Dayton Children's Hospital

Dayton, Ohio, 45404, United States

Location

The Toledo Hospital/Toledo Children's Hospital

Toledo, Ohio, 43606, United States

Location

Mercy Children's Hospital

Toledo, Ohio, 43608, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Natalie Warren Bryant Cancer Center at Saint Francis

Tulsa, Oklahoma, 74136, United States

Location

Legacy Emanuel Children's Hospital

Portland, Oregon, 97227, United States

Location

Legacy Emanuel Hospital and Health Center

Portland, Oregon, 97227, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Lehigh Valley Hospital - Muhlenberg

Bethlehem, Pennsylvania, 18017, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Palmetto Health Richland

Columbia, South Carolina, 29203, United States

Location

BI-LO Charities Children's Cancer Center

Greenville, South Carolina, 29605, United States

Location

Greenville Cancer Treatment Center

Greenville, South Carolina, 29605, United States

Location

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, 57117-5134, United States

Location

T C Thompson Children's Hospital

Chattanooga, Tennessee, 37403, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Texas Tech University Health Sciences Center-Amarillo

Amarillo, Texas, 79106, United States

Location

Driscoll Children's Hospital

Corpus Christi, Texas, 78411, United States

Location

Medical City Dallas Hospital

Dallas, Texas, 75230, United States

Location

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

Location

Brooke Army Medical Center

Fort Sam Houston, Texas, 78234, United States

Location

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

Location

Covenant Children's Hospital

Lubbock, Texas, 79410, United States

Location

Children's Hospital of San Antonio

San Antonio, Texas, 78207, United States

Location

Methodist Children's Hospital of South Texas

San Antonio, Texas, 78229, United States

Location

Scott and White Memorial Hospital

Temple, Texas, 76508, United States

Location

University of Vermont College of Medicine

Burlington, Vermont, 05405, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

Location

Children's Hospital of The King's Daughters

Norfolk, Virginia, 23507, United States

Location

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, 99204, United States

Location

Mary Bridge Children's Hospital and Health Center

Tacoma, Washington, 98405, United States

Location

Madigan Army Medical Center

Tacoma, Washington, 98431, United States

Location

West Virginia University Charleston Division

Charleston, West Virginia, 25304, United States

Location

West Virginia University Healthcare

Morgantown, West Virginia, 26506, United States

Location

Saint Vincent Hospital Cancer Center Green Bay

Green Bay, Wisconsin, 54301, United States

Location

Marshfield Medical Center-Marshfield

Marshfield, Wisconsin, 54449, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

British Columbia Children's Hospital

Vancouver, British Columbia, V6H 3V4, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Janeway Child Health Centre

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

Location

IWK Health Centre

Halifax, Nova Scotia, B3K 6R8, Canada

Location

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, L8N 3Z5, Canada

Location

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

Location

Children's Hospital

London, Ontario, N6A 5W9, Canada

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

The Montreal Children's Hospital of the MUHC

Montreal, Quebec, H3H 1P3, Canada

Location

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

San Jorge Children's Hospital

San Juan, 00912, Puerto Rico

Location

Related Publications (1)

  • Fisher BT, Zaoutis T, Dvorak CC, Nieder M, Zerr D, Wingard JR, Callahan C, Villaluna D, Chen L, Dang H, Esbenshade AJ, Alexander S, Wiley JM, Sung L. Effect of Caspofungin vs Fluconazole Prophylaxis on Invasive Fungal Disease Among Children and Young Adults With Acute Myeloid Leukemia: A Randomized Clinical Trial. JAMA. 2019 Nov 5;322(17):1673-1681. doi: 10.1001/jama.2019.15702.

Related Links

MeSH Terms

Conditions

Leukemia, Myeloid, AcuteLeukemia, Monocytic, AcuteLeukemia, Myelomonocytic, AcuteMycosesNeutropeniaLeukemiaInvasive Fungal Infections

Interventions

CaspofunginFluconazole

Condition Hierarchy (Ancestors)

Leukemia, MyeloidNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesBacterial Infections and MycosesInfectionsAgranulocytosisLeukopeniaCytopeniaLeukocyte Disorders

Intervention Hierarchy (Ancestors)

LipopeptidesLipidsPeptidesAmino Acids, Peptides, and ProteinsEchinocandinsPeptides, CyclicTriazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Results Point of Contact

Title
Results Reporting Coordinator
Organization
Children's Oncology Group

Study Officials

  • Theoklis E Zaoutis

    Children's Oncology Group

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
SUPPORTIVE CARE
Intervention Model
PARALLEL
Sponsor Type
NETWORK
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 1, 2011

First Posted

March 3, 2011

Study Start

April 4, 2011

Primary Completion

June 30, 2018

Study Completion

June 30, 2020

Last Updated

March 30, 2021

Results First Posted

September 17, 2019

Record last verified: 2019-06

Locations