A Randomized Open-Label Trial of Caspofungin Versus Fluconazole to Prevent Invasive Fungal Infections in Children Undergoing Chemotherapy for Acute Myeloid Leukemia (AML)
N/A
30 Years
Both
Fungal Infection, Leukemia, Neutropenia
Trial Information
A Randomized Open-Label Trial of Caspofungin Versus Fluconazole to Prevent Invasive Fungal Infections in Children Undergoing Chemotherapy for Acute Myeloid Leukemia (AML)
OBJECTIVES:
Primary
- To determine if prophylaxis with caspofungin administered during periods of neutropenia
following chemotherapy for acute myeloid leukemia (AML) is associated with a lower
incidence of proven or probable invasive fungal infections (IFI) compared with
fluconazole.
Secondary
- To determine if prophylaxis with caspofungin will result in a lower incidence of proven
or probable cases of invasive aspergillosis (IA) compared with fluconazole.
- To determine if prophylaxis with caspofungin will result in improved survival compared
to fluconazole.
- To determine if prophylaxis with caspofungin will result in less empiric antifungal
therapy compared to fluconazole.
- To determine the sensitivity, specificity, and positive and negative predictive value
of biweekly galactomannan (GM) and beta-D glucan testing in diagnosing IFI.
- To test the association between single nucleotide polymorphisms (SNPs) in genes
involved in innate immunity and proven or probable IFI.
- To develop predictive models of IFI using SNP in genes involved in immunity and
clinical covariates.
OUTLINE: This is a multicenter study. Patients are stratified according to disease (de novo
acute myeloid leukemia vs all other patients). Patients are randomized to 1 of 2 treatment
arms.
- Arm I: Patients receive caspofungin acetate IV over 1 hour once daily (QD) beginning
within 24-72 hours after the last dose of chemotherapy for each course and continuing
until ANC > 100-500/μL, the next chemotherapy course begins, or patient meets any
off-protocol criteria.
- Arm II: Patients receive fluconazole IV over 2 hours or orally (PO) QD beginning within
24-72 hours after the last dose of chemotherapy for each course and continuing until
ANC > 100-500/μL, the next chemotherapy course begins, or patient meets any
off-protocol criteria.
In both arms, treatment continues in the absence of invasive fungal infections or disease
progression.
Blood samples may be collected twice weekly for antifungal antigen assays and at the end of
course 1 for single nucleotide polymorphism analysis.
After completion of study treatment, patients are followed up periodically for 2 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- 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
- Planned treatment as per COG-AAML0531 (including those in whom it is planned to
not administer Intensification III) or AAML1031 for any diagnosis; either those
following these treatment plans or those enrolled on AAML1031 are eligible
- Patients with the following diagnoses are not eligible:
- Acute promyelocytic leukemia (APL)
- Down syndrome
- Juvenile myelomonocytic leukemia (JMML)
PATIENT CHARACTERISTICS:
- Creatinine clearance or radioisotope GFR ≥ 70 mL/min 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)
- ≤ 1.7 mg/dL (males age ≥ 16 years)
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age AND SGOT (AST) or SGPT
(ALT) < 2.5 x ULN
- Lactating patients must agree not to nurse a child while on this trial
- Female patients of childbearing age must have a negative pregnancy test
- Patients must agree to use an effective birth control method
- Patients with a documented history of IFI within the previous 30 days are not
eligible
- Patients with a history of echinocandin or fluconazole hypersensitivity are not
eligible
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No other concurrent systemic antifungal therapy
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Supportive Care
Outcome Measure:
Time to development of proven or probable invasive fungal infections (IFI) defined according to criteria developed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG)
Outcome Description:
Evaluated using Kaplan-Meier analyses. Log rank test will be used to assess if there is any benefit associated with caspofungin acetate compared to fluconazole. Compared between the 2 arms using Gray's test. Summary statistics such as means, standard deviations, medians, and ranges will be produced
Outcome Time Frame:
Assessed up to 2 years
Safety Issue:
No
Principal Investigator
Theoklis Zaoutis, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Children's Hospital of Philadelphia
Authority:
United States: Federal Government
Study ID:
ACCL0933
NCT ID:
NCT01307579
Start Date:
April 2011
Completion Date:
Related Keywords:
- Fungal Infection
- Leukemia
- Neutropenia
- fungal infection
- neutropenia
- childhood acute myeloid leukemia in remission
- recurrent childhood acute myeloid leukemia
- untreated childhood acute myeloid leukemia and other myeloid malignancies
- secondary acute myeloid leukemia
- adult acute myeloid leukemia in remission
- recurrent adult acute myeloid leukemia
- untreated adult acute myeloid leukemia
- adult acute minimally differentiated myeloid leukemia (M0)
- childhood acute minimally differentiated myeloid leukemia (M0)
- adult acute myeloblastic leukemia without maturation (M1)
- childhood acute myeloblastic leukemia without maturation (M1)
- adult acute myeloblastic leukemia with maturation (M2)
- childhood acute myeloblastic leukemia with maturation (M2)
- adult acute myelomonocytic leukemia (M4)
- childhood acute myelomonocytic leukemia (M4)
- adult acute monoblastic leukemia (M5a)
- adult acute monocytic leukemia (M5b)
- childhood acute monoblastic leukemia (M5a)
- childhood acute monocytic leukemia (M5b)
- adult erythroleukemia (M6a)
- adult pure erythroid leukemia (M6b)
- childhood acute erythroleukemia (M6)
- adult acute megakaryoblastic leukemia (M7)
- childhood acute megakaryocytic leukemia (M7)
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities
- adult acute myeloid leukemia with del(5q)
- adult acute myeloid leukemia with inv(16)(p13;q22)
- adult acute myeloid leukemia with t(16;16)(p13;q22)
- adult acute myeloid leukemia with t(8;21)(q22;q22)
- Leukemia
- Leukemia, Myeloid, Acute
- Leukemia, Myeloid
- Mycoses
- Neutropenia
Name | Location |
|---|---|
| Roswell Park Cancer Institute | Buffalo, New York 14263 |
| Children's Hospital of Philadelphia | Philadelphia, Pennsylvania 19104 |
| Mayo Clinic Cancer Center | Rochester, Minnesota 55905 |
| University of Chicago Cancer Research Center | Chicago, Illinois 60637 |
| Barbara Ann Karmanos Cancer Institute | Detroit, Michigan 48201 |
| Hurley Medical Center | Flint, Michigan 48503 |
| Medical City Dallas Hospital | Dallas, Texas 75230 |
| Presbyterian - St. Luke's Medical Center | Denver, Colorado 80218 |
| Van Elslander Cancer Center at St. John Hospital and Medical Center | Grosse Pointe Woods, Michigan 48236 |
| Bronson Methodist Hospital | Kalamazoo, Michigan 49007 |
| CCOP - MeritCare Hospital | Fargo, North Dakota 58122 |
| Natalie Warren Bryant Cancer Center at St. Francis Hospital | Tulsa, Oklahoma 74136 |
| Sanford Cancer Center at Sanford USD Medical Center | Sioux Falls, South Dakota 57117-5039 |
| Vanderbilt-Ingram Cancer Center | Nashville, Tennessee 37232-6838 |
| Marshfield Clinic - Marshfield Center | Marshfield, Wisconsin 54449 |
| Newark Beth Israel Medical Center | Newark, New Jersey 07112 |
| New York Medical College | Valhalla, New York 10595 |
| Holden Comprehensive Cancer Center at University of Iowa | Iowa City, Iowa 52242-1002 |
| Ellis Fischel Cancer Center at University of Missouri - Columbia | Columbia, Missouri 65203 |
| Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center | Lebanon, New Hampshire 03756-0002 |
| Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill | Chapel Hill, North Carolina 27599-7570 |
| CCOP - Scott and White Hospital | Temple, Texas 76508 |
| Cancer Research Center of Hawaii | Honolulu, Hawaii 96813 |
| Brooke Army Medical Center | Fort Sam Houston, Texas 78234-6200 |
| Children's Hospital of Orange County | Orange, California 92668 |
| Children's National Medical Center | Washington, District of Columbia 20010-2970 |
| Children's Mercy Hospital | Kansas City, Missouri 64108 |
| St. Joseph's Hospital and Medical Center | Paterson, New Jersey 07503 |
| Children's Hospital and Regional Medical Center - Seattle | Seattle, Washington 98105 |
| University of California Davis Cancer Center | Sacramento, California 95817 |
| Nemours Children's Clinic | Jacksonville, Florida 32207 |
| All Children's Hospital | St. Petersburg, Florida 33701 |
| Children's Memorial Hospital - Chicago | Chicago, Illinois 60614 |
| Children's Hospital of New Orleans | New Orleans, Louisiana 70118 |
| Cardinal Glennon Children's Hospital | Saint Louis, Missouri 63104 |
| Schneider Children's Hospital | New Hyde Park, New York 11042 |
| Driscoll Children's Hospital | Corpus Christi, Texas 78466 |
| Inova Fairfax Hospital | Falls Church, Virginia 22042-3300 |
| Fletcher Allen Health Care - University Health Center Campus | Burlington, Vermont 05401 |
| Southern California Permanente Medical Group | Downey, California 90242 |
| Children's Hospital Central California | Madera, California 93638-8762 |
| Kosair Children's Hospital | Louisville, Kentucky 40202-3830 |
| Palmetto Health South Carolina Cancer Center | Columbia, South Carolina 29203 |
| Children's Hospital of the King's Daughters | Norfolk, Virginia 23507 |
| Midwest Children's Cancer Center at Children's Hospital of Wisconsin | Milwaukee, Wisconsin 53226 |
| Arkansas Cancer Research Center at University of Arkansas for Medical Sciences | Little Rock, Arkansas 72205 |
| Blumenthal Cancer Center at Carolinas Medical Center | Charlotte, North Carolina 28232-2861 |
| Carol G. Simon Cancer Center at Morristown Memorial Hospital | Morristown, New Jersey 07962 |
| Winthrop University Hospital | Mineola, New York 11501 |
| Loma Linda University Cancer Institute at Loma Linda University Medical Center | Loma Linda, California 92354 |
| Jonathan Jaques Children's Cancer Center at Miller Children's Hospital | Long Beach, California 90801 |
| Yale Cancer Center | New Haven, Connecticut 06520-8028 |
| Lee Cancer Care of Lee Memorial Health System | Fort Myers, Florida 33901 |
| Broward General Medical Center Cancer Center | Ft. Lauderdale, Florida 33316 |
| Nemours Children's Clinic - Orlando | Orlando, Florida 32806 |
| Florida Hospital Cancer Institute at Florida Hospital Orlando | Orlando, Florida 32803-1273 |
| St. Joseph's Cancer Institute at St. Joseph's Hospital | Tampa, Florida 33607 |
| St. Vincent Indianapolis Hospital | Indianapolis, Indiana 46260 |
| Blank Children's Hospital | Des Moines, Iowa 50309 |
| Ochsner Cancer Institute at Ochsner Clinic Foundation | New Orleans, Louisiana 70121 |
| Alvin and Lois Lapidus Cancer Institute at Sinai Hospital | Baltimore, Maryland 21215 |
| Floating Hospital for Children at Tufts - New England Medical Center | Boston, Massachusetts 02111 |
| Breslin Cancer Center at Ingham Regional Medical Center | Lansing, Michigan 48910 |
| Hackensack University Medical Center Cancer Center | Hackensack, New Jersey 07601 |
| Albert Einstein Cancer Center at Albert Einstein College of Medicine | Bronx, New York 10461 |
| NYU Cancer Institute at New York University Medical Center | New York, New York 10016 |
| Stony Brook University Cancer Center | Stony Brook, New York 11794-8174 |
| SUNY Upstate Medical University Hospital | Syracuse, New York 13210 |
| Mission Hospitals - Memorial Campus | Asheville, North Carolina 28801 |
| Presbyterian Cancer Center at Presbyterian Hospital | Charlotte, North Carolina 28233-3549 |
| Wake Forest University Comprehensive Cancer Center | Winston-Salem, North Carolina 27157-1096 |
| Cincinnati Children's Hospital Medical Center | Cincinnati, Ohio 45229-3039 |
| Rainbow Babies and Children's Hospital | Cleveland, Ohio 44106-5000 |
| Toledo Hospital | Toledo, Ohio 43606 |
| Rhode Island Hospital Comprehensive Cancer Center | Providence, Rhode Island 02903 |
| Hollings Cancer Center at Medical University of South Carolina | Charleston, South Carolina 29425 |
| Texas Tech University Health Sciences Center School of Medicine - Amarillo | Amarillo, Texas 79106 |
| Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas | Dallas, Texas 75390 |
| Baylor University Medical Center - Houston | Houston, Texas 77030-2399 |
| Methodist Children's Hospital of South Texas | San Antonio, Texas 78229-3993 |
| Providence Cancer Center at Sacred Heart Medical Center | Spokane, Washington 99220-2555 |
| St. Vincent Hospital Regional Cancer Center | Green Bay, Wisconsin 54307-3508 |
| Saint Peter's University Hospital | New Brunswick, New Jersey 08901-1780 |
| James P. Wilmot Cancer Center at University of Rochester Medical Center | Rochester, New York 14642 |
| David C. Pratt Cancer Center at St. John's Mercy | St. Louis, Missouri 63141 |
| Greenebaum Cancer Center at University of Maryland Medical Center | Baltimore, Maryland 21201 |
| UNMC Eppley Cancer Center at the University of Nebraska Medical Center | Omaha, Nebraska 68198-7680 |
| Memorial Cancer Institute at Memorial Regional Hospital | Hollywood, Florida 33021 |
| Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center | Los Angeles, California 90048-1865 |
| Childrens Hospital Los Angeles | Los Angeles, California 90027 |
| Rady Children's Hospital - San Diego | San Diego, California 92123-4282 |
| UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco, California 94115 |
| Alfred I. duPont Hospital for Children | Wilmington, Delaware 19803 |
| AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus | Atlanta, Georgia 30322 |
| Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center | Savannah, Georgia 31403-3089 |
| Mountain States Tumor Institute at St. Luke's Regional Medical Center | Boise, Idaho 83712-6297 |
| University of Illinois Cancer Center | Chicago, Illinois 60612-7243 |
| Keyser Family Cancer Center at Advocate Hope Children's Hospital | Oak Lawn, Illinois 60453 |
| Simmons Cooper Cancer Institute | Springfield, Illinois 62794-9677 |
| Lucille P. Markey Cancer Center at University of Kentucky | Lexington, Kentucky 40536-0093 |
| Tulane Cancer Center Office of Clinical Research | Alexandria, Louisiana 71315-3198 |
| CancerCare of Maine at Eastern Maine Medical Center | Bangor, Maine 04401 |
| C.S. Mott Children's Hospital at University of Michigan Medical Center | Ann Arbor, Michigan 48109-0286 |
| Masonic Cancer Center at University of Minnesota | Minneapolis, Minnesota 55455 |
| Children's Hospitals and Clinics of Minnesota - Minneapolis | Minneapolis, Minnesota 55404 |
| University of Mississippi Cancer Clinic | Jackson, Mississippi 39216-4505 |
| Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis | St. Louis, Missouri 63110 |
| Children's Hospital | Omaha, Nebraska 68114-4113 |
| CCOP - Nevada Cancer Research Foundation | Las Vegas, Nevada 89109-2306 |
| St. Barnabas Medical Center Cancer Center | Livingston, New Jersey 07039 |
| Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School | New Brunswick, New Jersey 08903 |
| University of New Mexico Cancer Center | Albuquerque, New Mexico 87131-5636 |
| Albany Medical Center Hospital | Albany, New York 12208-3419 |
| Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center | New York, New York 10032 |
| Akron Children's Hospital | Akron, Ohio 44308-1062 |
| Nationwide Children's Hospital | Columbus, Ohio 43205-2696 |
| Dayton Children's - Dayton | Dayton, Ohio 45404-1815 |
| Oklahoma University Cancer Institute | Oklahoma City, Oklahoma 73104 |
| Knight Cancer Institute at Oregon Health and Science University | Portland, Oregon 97239-3098 |
| Geisinger Cancer Institute at Geisinger Health | Danville, Pennsylvania 17822-0001 |
| Children's Hospital of Pittsburgh of UPMC | Pittsburgh, Pennsylvania 15213 |
| Madigan Army Medical Center - Tacoma | Tacoma, Washington 98431 |
| Mary Bridge Children's Hospital and Health Center - Tacoma | Tacoma, Washington 98405 |
| West Virginia University Health Sciences Center - Charleston | Charleston, West Virginia 25302 |
| Riley's Children Cancer Center at Riley Hospital for Children | Indianapolis, Indiana 46202-5225 |
| University of Virginia Cancer Center | Charlottesville, Virginia 22908 |
| Duke Cancer Institute | Durham, North Carolina 27710 |
| T.C. Thompson Children's Hospital | Chattanooga, Tennessee 37403 |
| Connecticut Children's Medical Center | Hartford, Connecticut 06106 |
| Nemours Children's Clinic - Pensacola | Pensacola, Florida 32504 |
| Helen DeVos Children's Hospital at Spectrum Health | Grand Rapids, Michigan 49503 |
| Mercy Children's Hospital | Toledo, Ohio 43608 |
| Legacy Emanuel Children's Hospital | Portland, Oregon 97227 |
| BI-LO Charities Children's Cancer Center | Greenville, South Carolina 29605 |
| Children's Hospital of Alabama at University of Alabama at Birmingham | Birmingham, Alabama 35233 |
