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

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ClinicalTrials.gov Identifier: NCT01307579

Recruitment Status : Active, not recruiting

First Posted : March 3, 2011

Last Update Posted : August 7, 2018

Sponsor:

Collaborator:

National Cancer Institute (NCI)

Information provided by (Responsible Party):

Children's Oncology Group

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Acute Myeloid Leukemia Adult Acute Megakaryoblastic Leukemia Adult Acute Monoblastic Leukemia Adult Acute Monocytic Leukemia Adult Acute Myeloid Leukemia in Remission Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11 Adult Acute Myeloid Leukemia With Maturation Adult Acute Myeloid Leukemia With Minimal Differentiation Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11 Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1 Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A Adult Acute Myeloid Leukemia Without Maturation Adult Acute Myelomonocytic Leukemia Adult Erythroleukemia Adult Pure Erythroid Leukemia Alkylating Agent-Related Acute Myeloid Leukemia Childhood Acute Erythroid Leukemia Childhood Acute Megakaryoblastic Leukemia Childhood Acute Monoblastic Leukemia Childhood Acute Monocytic Leukemia Childhood Acute Myeloid Leukemia in Remission Childhood Acute Myeloid Leukemia With Maturation Childhood Acute Myeloid Leukemia With Minimal Differentiation Childhood Acute Myeloid Leukemia Without Maturation Childhood Acute Myelomonocytic Leukemia Fungal Infection Myeloid Neoplasm Neutropenia Recurrent Adult Acute Myeloid Leukemia Recurrent Childhood Acute Myeloid Leukemia Secondary Acute Myeloid Leukemia Untreated Adult Acute Myeloid Leukemia Untreated Childhood Myeloid Neoplasm	Drug: Caspofungin Acetate Drug: Fluconazole Other: Laboratory Biomarker Analysis	Phase 3

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.

Study Design


Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	575 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (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)
Actual Study Start Date :	April 4, 2011
Estimated Primary Completion Date :	December 31, 2018

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Core binding factor acute myeloid leukemia Cytogenetically normal acute myeloid leukemia Familial acute myeloid leukemia with mutated CEBPA

MedlinePlus related topics: Acute Myeloid Leukemia Fungal Infections Leukemia Molds

Drug Information available for: Fluconazole Caspofungin Caspofungin acetate

Genetic and Rare Diseases Information Center resources: Myeloid Leukemia Acute Myeloid Leukemia Acute Non Lymphoblastic Leukemia Granulocytopenia Acute Myeloblastic Leukemia Without Maturation Acute Myeloblastic Leukemia With Maturation Acute Erythroid Leukemia Acute Megakaryoblastic Leukemia Acute Myelomonocytic Leukemia Di Guglielmo's Syndrome Acute Monoblastic Leukemia Chronic Myelomonocytic Leukemia Myelodysplastic/myeloproliferative Disease Chronic Myeloproliferative Disorders

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
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 Name: Cancidas 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 Name: Diflucan Other: Laboratory Biomarker Analysis Correlative studies

Outcome Measures

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 ]
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 ]
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 ]
Standard survival analyses will be performed.
Total days of empiric antifungal therapy while a patient is receiving prophylaxis [ Time Frame: Up to 4 years ]
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 ]
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 ]
Impact of candidate gene SNPs will be determined using the log rank test.

Eligibility Criteria

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Ages Eligible for Study:	3 Months to 30 Years (Child, Adult)
Sexes Eligible for Study:	All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01307579

Show 179 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Theoklis Zaoutis	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 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) CDR0000695748 COG-ACCL0933 S12-00316 ACCL0933 ( Other Identifier: Childrens Oncology Group ) COG-ACCL0933 ( Other Identifier: DCP ) ACCL0933 ( Other Identifier: CTEP ) U10CA095861 ( U.S. NIH Grant/Contract ) UG1CA189955 ( U.S. NIH Grant/Contract )
First Posted:	March 3, 2011 Key Record Dates
Last Update Posted:	August 7, 2018
Last Verified:	January 2018

Additional relevant MeSH terms:


Leukemia Infection Communicable Diseases Neoplasms Leukemia, Myeloid Leukemia, Myeloid, Acute Leukemia, Myelomonocytic, Acute Leukemia, Myelomonocytic, Chronic Neutropenia Mycoses Leukemia, Monocytic, Acute Invasive Fungal Infections Leukemia, Megakaryoblastic, Acute Leukemia, Erythroblastic, Acute Neoplasms by Histologic Type	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

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