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

Study ID
ACCL0933

Cancer Related
Yes

Healthy Volunteers
No

Study Sites

  • Children’s Medical Center (Dallas, Plano, Southlake)

Contact
Stephanie McGinn
214 456-8588
stephanie.mcginn@childrens.com

Principal Investigator
Naomi Winick, M.D.

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)

Brief Overview


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.

Summary


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.

Participant Eligibility


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