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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.
Verified May 2013 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: May 30, 2013
Last verified: May 2013
History of Changes
  Purpose

RATIONALE: 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.

PURPOSE: This randomized phase III clinical trial is studying 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.


Condition Intervention Phase
Fungal Infection
Leukemia
Neutropenia
 Drug: caspofungin acetate
Drug: fluconazole
 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 invasive fungal infections (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. Compared between the 2 arms using Gray's test. 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. Compared between the 2 arms using Gray's test. 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: 550
Study Start Date: April 2011
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (caspofungin acetate)
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/μL (recommended > 200/μL for 2 consecutive days) or the next chemotherapy course begins.
 Drug: caspofungin acetate
Given IV
Other Names:
  • Cancidas
  • L-743
  • 873
  • MK-0991
Active Comparator: Arm II (fluconazole)
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/μL (recommended > 200/μL for 2 consecutive days) or the next chemotherapy course begins.
 Drug: fluconazole
Given IV or orally
Other Names:
  • 4- triazole-1-ethanol
  • Diflucan
  • FCZ

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01307579

  Show 147 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Study Chair: Theoklis Zaoutis, MD Children's Hospital of Philadelphia
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT01307579     History of Changes
Other Study ID Numbers: ACCL0933, COG-ACCL0933, CDR0000695748
Study First Received: March 1, 2011
Last Updated: May 30, 2013
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
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)

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Mycoses
Neutropenia
Neoplasms by Histologic Type
Neoplasms
Agranulocytosis
Leukopenia
Leukocyte Disorders
Hematologic Diseases
 Fluconazole
Caspofungin
Echinocandins
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on June 18, 2013