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

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 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:

Genetics Home Reference related topics: cyclic neutropenia familial acute myeloid leukemia with mutated CEBPA

MedlinePlus related topics: Acute Myeloid Leukemia Cancer Fungal Infections Leukemia Molds

Drug Information available for: Fluconazole Caspofungin Caspofungin acetate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

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) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Development of proven or probably invasive aspergillosis (IA) defined according to the criteria developed by the EORTC/MSG [ Designated as safety issue: No ]
Death due to any cause [ Designated as safety issue: No ]
Need for empiric antifungal therapy defined as the institution of antifungal therapy while a patient is receiving prophylaxis [ Designated as safety issue: No ]
Results from galactomannan and beta-D glucan assays for the diagnosis of IFI or IA alone [ Designated as safety issue: No ]
Results of the genotyping assays for single nucleotide polymorphism analysis [ Designated as safety issue: No ]

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 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.	Drug: caspofungin acetate Given IV
Active Comparator: 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.	Drug: fluconazole Given IV or orally

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:	Gregory H. Reaman, Children's Oncology Group - Group Chair Office
ClinicalTrials.gov Identifier:	NCT01307579 History of Changes
Other Study ID Numbers:	CDR0000695748, COG-ACCL0933
Study First Received:	March 1, 2011
Last Updated:	November 22, 2012
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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 May 19, 2013