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Caspofungin Acetate or Fluconazole in Preventing Invasive Fungal Infections in Patients With Acute Myeloid Leukemia Who Are Undergoing Chemotherapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by Children's Oncology Group
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT01307579
First received: March 1, 2011
Last updated: August 23, 2016
Last verified: August 2016
History of Changes
  Purpose
This randomized phase III trial studies caspofungin acetate to see how it works compared to fluconazole in preventing invasive fungal infections in patients with acute myeloid leukemia who are undergoing chemotherapy. Caspofungin acetate or fluconazole may help prevent fungal infections caused by chemotherapy. It is not yet known whether fluconazole is more effective than caspofungin acetate in preventing fungal infections in patients with acute myeloid leukemia who are undergoing chemotherapy.

Condition Intervention Phase
Adult Acute Megakaryoblastic Leukemia (M7)
Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
Adult Acute Monoblastic Leukemia (M5a)
Adult Acute Monocytic Leukemia (M5b)
Adult Acute Myeloblastic Leukemia With Maturation (M2)
Adult Acute Myeloblastic Leukemia Without Maturation (M1)
Adult Acute Myeloid Leukemia in Remission
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)
Adult Acute Myelomonocytic Leukemia (M4)
Adult Erythroleukemia (M6a)
Adult Pure Erythroid Leukemia (M6b)
Childhood Acute Erythroleukemia (M6)
Childhood Acute Megakaryocytic Leukemia (M7)
Childhood Acute Minimally Differentiated Myeloid Leukemia (M0)
Childhood Acute Monoblastic Leukemia (M5a)
Childhood Acute Monocytic Leukemia (M5b)
Childhood Acute Myeloblastic Leukemia With Maturation (M2)
Childhood Acute Myeloblastic Leukemia Without Maturation (M1)
Childhood Acute Myeloid Leukemia in Remission
Childhood Acute Myelomonocytic Leukemia (M4)
Fungal Infection
Neutropenia
Recurrent Adult Acute Myeloid Leukemia
Recurrent Childhood Acute Myeloid Leukemia
Secondary Acute Myeloid Leukemia
Untreated Adult Acute Myeloid Leukemia
Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies
 Drug: caspofungin acetate
Drug: fluconazole
Other: laboratory biomarker analysis
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: A Randomized Open-Label Trial of Caspofungin Versus Fluconazole to Prevent Invasive Fungal Infections in Children Undergoing Chemotherapy for Acute Myeloid Leukemia (AML)

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Time to development of proven or probable IFI, defined according to criteria developed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) [ Time Frame: Assessed up to 2 years ] [ Designated as safety issue: No ]
    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. Gray's test will be used to compare the cumulative incidence function between the 2 arms. Summary statistics such as means, standard deviations, medians, and ranges will be produced.


Secondary Outcome Measures:
  • Time to development of proven or probably invasive aspergillosis (IA), defined according to the criteria developed by the EORTC/MSG [ Time Frame: Assessed up to 2 years ] [ Designated as safety issue: No ]
    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. Gray's test will be used to compare the cumulative incidence function between the 2 arms. Summary statistics such as means, standard deviations, medians, and ranges will be produced.

  • Time to death due to any cause [ Time Frame: Assessed up to 2 years ] [ Designated as safety issue: No ]
    Standard survival analyses will be performed.

  • Total days of empiric antifungal therapy while a patient is receiving prophylaxis [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Compared between the 2 arms using t-test or Wilcoxon rank sum test.

  • Sensitivity, specificity, positive predictive value, and negative predictive value of the galactomannan and beta-D glucan assays for the diagnosis of IFI or IA alone [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Determined using standard formulas and EORTC/MSG criteria as the gold standard. Calculated using STATA statistical software version 11.0.

  • Results of the genotyping assays for single nucleotide polymorphism analysis [ Time Frame: At the end of course 1 ] [ Designated as safety issue: No ]
    Impact of candidate gene SNPs will be determined using the log rank test.
Estimated Enrollment: 575
Study Start Date: April 2011
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (caspofungin acetate)
Patients receive caspofungin acetate IV over 1 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 acetate
Given IV
Other Names:
  • Cancidas
  • L-743,873
  • MK-0991
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: Arm II (fluconazole)
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 and continuing until ANC > 100-500/uL following the nadir or the next chemotherapy course begins.
 Drug: fluconazole
Given IV or PO
Other Names:
  • Diflucan
  • FCZ
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine if prophylaxis with caspofungin (caspofungin acetate) 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 OBJECTIVES:

I. To determine if prophylaxis with caspofungin will result in a lower incidence of proven or probable cases of invasive aspergillosis (IA) compared with fluconazole. (Clinical) II. To determine if prophylaxis with caspofungin will result in improved survival compared to fluconazole. (Clinical) III. To determine if prophylaxis with caspofungin will result in less empiric antifungal therapy compared to fluconazole. (Clinical) IV. To determine the sensitivity, specificity, and positive and negative predictive value of biweekly galactomannan (GM) and beta-D glucan testing in diagnosing IFI. (Biological) V. To test the association between single nucleotide polymorphisms (SNPs) in genes involved in innate immunity and proven or probable IFI. (Biological) VI. To develop predictive models of IFI using SNP in genes involved in immunity and clinical covariates. (Biological)

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 24-72 hours following the last dose of chemotherapy for each course and continuing until absolute neutrophil count (ANC) > 100-500/uL following the nadir or the next chemotherapy course begins.

ARM II: Patients receive fluconazole IV over 1-2 hours or orally (PO) 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.

In both arms, treatment continues in the absence of invasive fungal infections or disease progression.

After completion of study treatment, patients are followed up periodically.

  Eligibility
Ages Eligible for Study:   3 Months to 30 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)
    • =< 1.7 mg/dL (males age >= 16 years)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x ULN for age
  • All patients and/or their parents or legal guardians must sign a written informed consent

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01307579

  Show 172 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Principal Investigator: Theoklis Zaoutis, MD MSCE Children's Oncology Group
  More Information

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT01307579     History of Changes
Other Study ID Numbers: ACCL0933  NCI-2011-02640  CDR0000695748  COG-ACCL0933  ACCL0933  COG-ACCL0933  ACCL0933  U10CA095861 
Study First Received: March 1, 2011
Last Updated: August 23, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Infection
Communicable Diseases
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Neutropenia
Mycoses
Leukemia, Monocytic, Acute
Leukemia, Erythroblastic, Acute
Leukemia, Megakaryoblastic, Acute
Neoplasms by Histologic Type
Neoplasms
Myelodysplastic-Myeloproliferative Diseases
 Bone Marrow Diseases
Hematologic Diseases
Agranulocytosis
Leukopenia
Leukocyte Disorders
Myeloproliferative Disorders
Fluconazole
Caspofungin
Echinocandins
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 29, 2016