Summary

for people ages 3 months to 30 years (full criteria)
at San Francisco, California and other locations
study started
estimated completion

Description

Summary

This randomized phase III trial compares the effectiveness of caspofungin to fluconazole in preventing invasive fungal infections in patients receiving chemotherapy for acute myeloid leukemia (AML). Antifungal prophylaxis is considered standard of care in children and adults with prolonged neutropenia after chemotherapy for AML however the ideal antifungal agent for prophylaxis in children is not known. Caspofungin has activity against yeast and some molds while fluconazole coverage is limited to just yeasts. Adult randomized trials suggest that agents with activity against yeasts and molds are more effective than those with just activity against yeasts. There are limited data to answer this comparative question in children. This study will establish much needed pediatric data to guide clinical decision making on optimal antifungal prophylaxis.

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)

Details

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Keywords

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 Pediatrics leukemia invasive fungal infection Infection Communicable Diseases Mycoses Invasive Fungal Infections Leukemia, Myeloid Leukemia, Myeloid, Acute Leukemia, Myelomonocytic, Acute Leukemia, Myelomonocytic, Chronic Leukemia, Monocytic, Acute Neoplasms Fluconazole Caspofungin Caspofungin Acetate Laboratory Biomarker Analysis

Eligibility

You can join if…

Open to people ages 3 months to 30 years

  • 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 m2 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

You CAN'T join if...

  • 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

Locations

  • UCSF Medical Center-Parnassus
    San Francisco California 94143 United States
  • UCSF Medical Center-Mission Bay
    San Francisco California 94158 United States

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Children's Oncology Group
ID
NCT01307579
Phase
Phase 3
Study Type
Interventional
Last Updated