Caspofungin Versus Fluconazole in Preventing Invasive Fungal Infections (IFI) in Patients Undergoing Chemotherapy for Acute Myeloid Leukemia
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ClinicalTrials.gov Identifier: NCT01307579 |
Recruitment Status :
Completed
First Posted : March 3, 2011
Results First Posted : September 17, 2019
Last Update Posted : March 30, 2021
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Condition or disease | Intervention/treatment | Phase |
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Acute Myeloid 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 Alkylating Agent-Related Acute Myeloid 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 |
PRIMARY OBJECTIVES:
I. 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 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 one of two treatment arms during their first chemotherapy course for AML.
ARM I: Patients receive caspofungin acetate intravenously (IV) over one 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.
Protocol prophylaxis was continued in both arms, until ANC increased to > 100-500/uL following the nadir or the next chemotherapy course began. Prophylaxis was given for all courses of planned AML chemotherapy or until the patient met one of the following off-protocol therapy criteria: development of proven or probable IFI according to institutional diagnosis, initiation of conditioning for hematopoietic cell transplantation, initiation of a new chemotherapy regimen for relapsed or refractory AML, refusal of further protocol therapy by patient, parent or guardian, or physician determines it is in the best interest of the patient.
Regardless of duration of prophylaxis, subjects in both arms are monitored for IFI until the earliest of the following criteria is met: two weeks after recovery of neutropenia following the last planned AML chemotherapy course, initiation of conditioning for hematopoietic cell transplantation, initiation of a new chemotherapy regimen for relapsed or refractory AML, withdrawal of consent for any further data submission, or death.
Patients were followed for overall survival up to two years from enrollment.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 517 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 |
Actual Primary Completion Date : | June 30, 2018 |
Actual Study Completion Date : | June 30, 2020 |

Arm | Intervention/treatment |
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Experimental: Arm I (caspofungin acetate)
Patients receive caspofungin acetate IV over one 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.
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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.
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Drug: Fluconazole
Given IV or PO
Other Name: Diflucan Other: Laboratory Biomarker Analysis Correlative studies |
- Percentage of Participants With Proven or Probable Invasive Fungal Infections (IFI) [ Time Frame: Up to 5 months since enrollment ]Proven or probable IFI is defined according to criteria developed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG).
- Percentage of Participants With Proven or Probable Invasive Aspergillosis (IA) [ Time Frame: Up to 5 months since enrollment ]Proven or probable invasive aspergillosis (IA) is defined according to the criteria developed by the EORTC/MSG. Kaplan Meier approach will used to estimate the incidence.
- Overall Survival [ Time Frame: Up to 2 years post enrollment ]Kaplan Meier method will be used to estimate overall survival. Time to event is from enrollment to date of death (by any cause). Participants are censored at last contact or 2 years anniversary of enrollment into this study, whichever occurred first.
- Percentage of Participants That Need Empiric Antifungal Therapy [ Time Frame: Up to 5 months since enrollment ]The percentage of participants requiring empiric antifungal therapy will be determined based on the presence of prolonged fever and neutropenia during each neutropenia course.
- Sensitivity of Galactomannan and Beta-D Glucan Assays for the Diagnosis of Proven or Probable IFI [ Time Frame: Up to 5 months since enrollment ]Sensitivity for the diagnosis of proven or probable IFI will be determined for the fungal biomarkers galactomannan and beta-D glucan assays. Sensitivity will be estimated for the combination of the two fungal biomarkers.
- Specificity of Galactomannan and Beta-D Glucan Assays for the Diagnosis of Proven or Probable IFI [ Time Frame: Up to 5 months since enrollment ]Specificity of galactomannan and beta-D glucan assays for the diagnosis of proven or probable IFI. Specificity will be estimated for the two fungal biomarkers together.
- Positive Predictive Value of Galactomannan and Beta-D Glucan Assays for the Diagnosis of Proven or Probable IFI [ Time Frame: Up to 5 months since enrollment ]Positive predictive value of galactomannan and beta-D glucan assays for the diagnosis of proven or probable IFI. Positive predictive value will be estimated for the two fungal biomarkers together.
- Negative Predictive Value of Galactomannan and Beta-D Glucan Assays for the Diagnosis of Proven or Probable IFI [ Time Frame: Up to 5 months since enrollment ]Negative predictive value of galactomannan and beta-D glucan assays for the diagnosis of proven or probable IFI. Negative predictive value will be estimated for the two fungal biomarkers together.
- Genotyping Assays for Single Nucleotide Polymorphism Analysis [ Time Frame: Up to 2 years post enrollment ]Descriptive statistics will be used to summarize the prevalence of single nucleotide polymorphisms.

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Ages Eligible for Study: | 3 Months to 30 Years (Child, Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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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
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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 AND 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:
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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

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

Principal Investigator: | Theoklis E Zaoutis | Children's Oncology Group |
Documents provided by Children's Oncology Group:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Children's Oncology Group |
ClinicalTrials.gov Identifier: | NCT01307579 |
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 |
Results First Posted: | September 17, 2019 |
Last Update Posted: | March 30, 2021 |
Last Verified: | June 2019 |
Pediatrics leukemia invasive fungal infection |
Infections Communicable Diseases Mycoses Invasive Fungal Infections Leukemia Neoplasms Leukemia, Myeloid Leukemia, Myeloid, Acute Leukemia, Myelomonocytic, Acute Leukemia, Myelomonocytic, Chronic Leukemia, Monocytic, Acute Neutropenia Neoplasms by Histologic Type Disease Attributes Pathologic Processes |
Myelodysplastic-Myeloproliferative Diseases Bone Marrow Diseases Hematologic Diseases Agranulocytosis Leukopenia Leukocyte Disorders Bacterial Infections and Mycoses Fluconazole Caspofungin Antifungal Agents Anti-Infective Agents 14-alpha Demethylase Inhibitors Cytochrome P-450 Enzyme Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |