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A Randomized Open-Label Trial of Caspofungin Versus Fluconazole to Prevent Invasive Fungal Infections in Children Undergoing Chemotherapy for Acute Myeloid Leukemia (AML)


Phase 3
N/A
30 Years
Open (Enrolling)
Both
Fungal Infection, Leukemia, Neutropenia

Thank you

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 InstituteBuffalo, New York  14263
Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
Mayo Clinic Cancer CenterRochester, Minnesota  55905
University of Chicago Cancer Research CenterChicago, Illinois  60637
Barbara Ann Karmanos Cancer InstituteDetroit, Michigan  48201
Hurley Medical CenterFlint, Michigan  48503
Medical City Dallas HospitalDallas, Texas  75230
Presbyterian - St. Luke's Medical CenterDenver, Colorado  80218
Van Elslander Cancer Center at St. John Hospital and Medical CenterGrosse Pointe Woods, Michigan  48236
Bronson Methodist HospitalKalamazoo, Michigan  49007
CCOP - MeritCare HospitalFargo, North Dakota  58122
Natalie Warren Bryant Cancer Center at St. Francis HospitalTulsa, Oklahoma  74136
Sanford Cancer Center at Sanford USD Medical CenterSioux Falls, South Dakota  57117-5039
Vanderbilt-Ingram Cancer CenterNashville, Tennessee  37232-6838
Marshfield Clinic - Marshfield CenterMarshfield, Wisconsin  54449
Newark Beth Israel Medical CenterNewark, New Jersey  07112
New York Medical CollegeValhalla, New York  10595
Holden Comprehensive Cancer Center at University of IowaIowa City, Iowa  52242-1002
Ellis Fischel Cancer Center at University of Missouri - ColumbiaColumbia, Missouri  65203
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical CenterLebanon, New Hampshire  03756-0002
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel Hill, North Carolina  27599-7570
CCOP - Scott and White HospitalTemple, Texas  76508
Cancer Research Center of HawaiiHonolulu, Hawaii  96813
Brooke Army Medical CenterFort Sam Houston, Texas  78234-6200
Children's Hospital of Orange CountyOrange, California  92668
Children's National Medical CenterWashington, District of Columbia  20010-2970
Children's Mercy HospitalKansas City, Missouri  64108
St. Joseph's Hospital and Medical CenterPaterson, New Jersey  07503
Children's Hospital and Regional Medical Center - SeattleSeattle, Washington  98105
University of California Davis Cancer CenterSacramento, California  95817
Nemours Children's ClinicJacksonville, Florida  32207
All Children's HospitalSt. Petersburg, Florida  33701
Children's Memorial Hospital - ChicagoChicago, Illinois  60614
Children's Hospital of New OrleansNew Orleans, Louisiana  70118
Cardinal Glennon Children's HospitalSaint Louis, Missouri  63104
Schneider Children's HospitalNew Hyde Park, New York  11042
Driscoll Children's HospitalCorpus Christi, Texas  78466
Inova Fairfax HospitalFalls Church, Virginia  22042-3300
Fletcher Allen Health Care - University Health Center CampusBurlington, Vermont  05401
Southern California Permanente Medical GroupDowney, California  90242
Children's Hospital Central CaliforniaMadera, California  93638-8762
Kosair Children's HospitalLouisville, Kentucky  40202-3830
Palmetto Health South Carolina Cancer CenterColumbia, South Carolina  29203
Children's Hospital of the King's DaughtersNorfolk, Virginia  23507
Midwest Children's Cancer Center at Children's Hospital of WisconsinMilwaukee, Wisconsin  53226
Arkansas Cancer Research Center at University of Arkansas for Medical SciencesLittle Rock, Arkansas  72205
Blumenthal Cancer Center at Carolinas Medical CenterCharlotte, North Carolina  28232-2861
Carol G. Simon Cancer Center at Morristown Memorial HospitalMorristown, New Jersey  07962
Winthrop University HospitalMineola, New York  11501
Loma Linda University Cancer Institute at Loma Linda University Medical CenterLoma Linda, California  92354
Jonathan Jaques Children's Cancer Center at Miller Children's HospitalLong Beach, California  90801
Yale Cancer CenterNew Haven, Connecticut  06520-8028
Lee Cancer Care of Lee Memorial Health SystemFort Myers, Florida  33901
Broward General Medical Center Cancer CenterFt. Lauderdale, Florida  33316
Nemours Children's Clinic - OrlandoOrlando, Florida  32806
Florida Hospital Cancer Institute at Florida Hospital OrlandoOrlando, Florida  32803-1273
St. Joseph's Cancer Institute at St. Joseph's HospitalTampa, Florida  33607
St. Vincent Indianapolis HospitalIndianapolis, Indiana  46260
Blank Children's HospitalDes Moines, Iowa  50309
Ochsner Cancer Institute at Ochsner Clinic FoundationNew Orleans, Louisiana  70121
Alvin and Lois Lapidus Cancer Institute at Sinai HospitalBaltimore, Maryland  21215
Floating Hospital for Children at Tufts - New England Medical CenterBoston, Massachusetts  02111
Breslin Cancer Center at Ingham Regional Medical CenterLansing, Michigan  48910
Hackensack University Medical Center Cancer CenterHackensack, New Jersey  07601
Albert Einstein Cancer Center at Albert Einstein College of MedicineBronx, New York  10461
NYU Cancer Institute at New York University Medical CenterNew York, New York  10016
Stony Brook University Cancer CenterStony Brook, New York  11794-8174
SUNY Upstate Medical University HospitalSyracuse, New York  13210
Mission Hospitals - Memorial CampusAsheville, North Carolina  28801
Presbyterian Cancer Center at Presbyterian HospitalCharlotte, North Carolina  28233-3549
Wake Forest University Comprehensive Cancer CenterWinston-Salem, North Carolina  27157-1096
Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039
Rainbow Babies and Children's HospitalCleveland, Ohio  44106-5000
Toledo HospitalToledo, Ohio  43606
Rhode Island Hospital Comprehensive Cancer CenterProvidence, Rhode Island  02903
Hollings Cancer Center at Medical University of South CarolinaCharleston, South Carolina  29425
Texas Tech University Health Sciences Center School of Medicine - AmarilloAmarillo, Texas  79106
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - DallasDallas, Texas  75390
Baylor University Medical Center - HoustonHouston, Texas  77030-2399
Methodist Children's Hospital of South TexasSan Antonio, Texas  78229-3993
Providence Cancer Center at Sacred Heart Medical CenterSpokane, Washington  99220-2555
St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54307-3508
Saint Peter's University HospitalNew Brunswick, New Jersey  08901-1780
James P. Wilmot Cancer Center at University of Rochester Medical CenterRochester, New York  14642
David C. Pratt Cancer Center at St. John's MercySt. Louis, Missouri  63141
Greenebaum Cancer Center at University of Maryland Medical CenterBaltimore, Maryland  21201
UNMC Eppley Cancer Center at the University of Nebraska Medical CenterOmaha, Nebraska  68198-7680
Memorial Cancer Institute at Memorial Regional HospitalHollywood, Florida  33021
Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical CenterLos Angeles, California  90048-1865
Childrens Hospital Los AngelesLos Angeles, California  90027
Rady Children's Hospital - San DiegoSan Diego, California  92123-4282
UCSF Helen Diller Family Comprehensive Cancer CenterSan Francisco, California  94115
Alfred I. duPont Hospital for ChildrenWilmington, Delaware  19803
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston CampusAtlanta, Georgia  30322
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical CenterSavannah, Georgia  31403-3089
Mountain States Tumor Institute at St. Luke's Regional Medical CenterBoise, Idaho  83712-6297
University of Illinois Cancer CenterChicago, Illinois  60612-7243
Keyser Family Cancer Center at Advocate Hope Children's HospitalOak Lawn, Illinois  60453
Simmons Cooper Cancer InstituteSpringfield, Illinois  62794-9677
Lucille P. Markey Cancer Center at University of KentuckyLexington, Kentucky  40536-0093
Tulane Cancer Center Office of Clinical ResearchAlexandria, Louisiana  71315-3198
CancerCare of Maine at Eastern Maine Medical CenterBangor, Maine  04401
C.S. Mott Children's Hospital at University of Michigan Medical CenterAnn Arbor, Michigan  48109-0286
Masonic Cancer Center at University of MinnesotaMinneapolis, Minnesota  55455
Children's Hospitals and Clinics of Minnesota - MinneapolisMinneapolis, Minnesota  55404
University of Mississippi Cancer ClinicJackson, Mississippi  39216-4505
Siteman Cancer Center at Barnes-Jewish Hospital - Saint LouisSt. Louis, Missouri  63110
Children's HospitalOmaha, Nebraska  68114-4113
CCOP - Nevada Cancer Research FoundationLas Vegas, Nevada  89109-2306
St. Barnabas Medical Center Cancer CenterLivingston, New Jersey  07039
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical SchoolNew Brunswick, New Jersey  08903
University of New Mexico Cancer CenterAlbuquerque, New Mexico  87131-5636
Albany Medical Center HospitalAlbany, New York  12208-3419
Herbert Irving Comprehensive Cancer Center at Columbia University Medical CenterNew York, New York  10032
Akron Children's HospitalAkron, Ohio  44308-1062
Nationwide Children's HospitalColumbus, Ohio  43205-2696
Dayton Children's - DaytonDayton, Ohio  45404-1815
Oklahoma University Cancer InstituteOklahoma City, Oklahoma  73104
Knight Cancer Institute at Oregon Health and Science UniversityPortland, Oregon  97239-3098
Geisinger Cancer Institute at Geisinger HealthDanville, Pennsylvania  17822-0001
Children's Hospital of Pittsburgh of UPMCPittsburgh, Pennsylvania  15213
Madigan Army Medical Center - TacomaTacoma, Washington  98431
Mary Bridge Children's Hospital and Health Center - TacomaTacoma, Washington  98405
West Virginia University Health Sciences Center - CharlestonCharleston, West Virginia  25302
Riley's Children Cancer Center at Riley Hospital for ChildrenIndianapolis, Indiana  46202-5225
University of Virginia Cancer CenterCharlottesville, Virginia  22908
Duke Cancer InstituteDurham, North Carolina  27710
T.C. Thompson Children's HospitalChattanooga, Tennessee  37403
Connecticut Children's Medical CenterHartford, Connecticut  06106
Nemours Children's Clinic - PensacolaPensacola, Florida  32504
Helen DeVos Children's Hospital at Spectrum HealthGrand Rapids, Michigan  49503
Mercy Children's HospitalToledo, Ohio  43608
Legacy Emanuel Children's HospitalPortland, Oregon  97227
BI-LO Charities Children's Cancer CenterGreenville, South Carolina  29605
Children's Hospital of Alabama at University of Alabama at BirminghamBirmingham, Alabama  35233