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

Conditions

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

Trial Phase

Phase 3

Trial Purpose and Description

Trial 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. 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.


Trial 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.

II. To determine if prophylaxis with caspofungin will result in improved survival compared to fluconazole.

III. To determine if prophylaxis with caspofungin will result in less empiric antifungal therapy compared to fluconazole.

IV. To determine the sensitivity, specificity, and positive and negative predictive value of biweekly galactomannan (GM) and beta-D glucan testing in diagnosing IFI. V. To test the association between single nucleotide polymorphisms (SNPs) in genes involved in innate immunity and proven or probable IFI.

VI. 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 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) is 100-500/μL following the nadir or the next chemotherapy course begins.

ARM II: Patients receive fluconazole IV over 2 hours or orally (PO) QD beginning within 24-72 hours following the last dose of chemotherapy for each course and continuing until absolute neutrophil count (ANC) is 100-500/μL following the nadir or the next chemotherapy course begins.

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.


Participation Guidelines

Age:
3 Months - 30 Years
Gender:
Both

Eligibility 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 glutamic 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
Sponsor:
Children's Oncology Group
National Cancer Institute (NCI)
Dates:
April 2011
Last Updated:
February 5, 2014
Study HIC#:
1112009412

Clinicaltrials.gov ID: NCT01307579