Caspofungin Acetate or Fluconazole in Preventing Invasive Fungal Infections in Patients With Acute Myeloid Leukemia Who Are Undergoing Chemotherapy
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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) |
- 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.
- 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:
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:
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 |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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 LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT01307579
Show 172 Study Locations
| Principal Investigator: | Theoklis Zaoutis, MD MSCE | Children's Oncology Group |
More Information
No publications provided
| 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: | January 8, 2015 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Communicable Diseases Infection Leukemia Leukemia, Erythroblastic, Acute Leukemia, Megakaryoblastic, Acute Leukemia, Monocytic, Acute Leukemia, Myeloid Leukemia, Myeloid, Acute Leukemia, Myelomonocytic, Acute Leukemia, Myelomonocytic, Chronic Mycoses Bone Marrow Diseases Hematologic Diseases Myelodysplastic-Myeloproliferative Diseases |
Myeloproliferative Disorders Neoplasms Neoplasms by Histologic Type Caspofungin Echinocandins Fluconazole 14-alpha Demethylase Inhibitors Anti-Infective Agents Antifungal Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Therapeutic Uses |
ClinicalTrials.gov processed this record on March 01, 2015