Voriconazole or Placebo in the Prophylaxis of Lung Infiltrates in Patients Undergoing Induction Chemotherapy for Acute Myelogenous Leukemia

Condition(s) targeted: Leukemia, Myelocytic, Acute

Intervention: voriconazole (Drug)

Phase: Phase 3

Status: Terminated

Sponsored by: University of Cologne

Official(s) and/or principal investigator(s):
Oliver A. Cornely, MD, Principal Investigator, Affiliation: Klinikum der Universität Köln

The purpose of the study is to determine whether voriconazole is as effective as antifungal prophylaxis in patients undergoing chemotherapy for acute myelogenous leukemia (AML).

Hypothesis: Voriconazole is superior to placebo in the prophylaxis of lung infiltrates until day 21 after the start of induction chemotherapy.

Official title: Phase III Study of Safety, Tolerance, Efficacy, Pharmacokinetics, and Costs of Therapy With Voriconazole or Placebo in the Prophylaxis of Lung Infiltrates in Patients Undergoing Induction Chemotherapy for Acute Myelogenous Leukemia

Study design: Prevention, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: To determine the incidence of lung infiltrates until day 21 among patients undergoing the first induction chemotherapy for acute myelogenous leukemia who are randomized to prophylactic voriconazole or placebo

Secondary outcome:

To determine and compare between study arms the: incidence of fever and other signs of infection

incidence and type of documented bacteremia

rate of patients with systemic open-label antifungal therapy

time to initiation of systemic open-label antifungal therapy

duration of absolute neutrophil count < 500/µl

rate and type of proven, probable and possible breakthrough invasive fungal infections

rate of patients with fever of unknown origin

incidence and severity of adverse events

trough voriconazole plasma level after day 8 of study treatment

direct costs of systemic antibiotics, antifungals and antivirals and diagnostic imaging

overall costs in terms of the diagnosis related groups applied to the study patients

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

1. Newly diagnosed or relapsed, de novo or secondary AML

2. First induction chemotherapy cycle

3. Expected neutropenic phase of a minimum duration of 10 days

4. Age >= 18 years

5. Legally signed consent form

Exclusion Criteria:

1. Known proven, probable or possible invasive fungal infection at randomization or in patient history

2. Computed tomography (CT) with any signs of a fungal infection according to the European Organisation for the Research and Treatment of Cancer (EORTC)/Mycosis Study Group (MSG) criteria, i. e. with any infiltrate (Ascioglu, et al 2002)

3. Any current fever unless explained by non-infectious causes

4. Antibacterial prophylaxis other than TMP/SMX

5. Liver function test [LFT] (AST/ALT/bilirubin) more than 3x the upper normal limit

6. Subjects who are receiving and cannot discontinue one of the following drugs at least 24 hours prior to randomization:

- Drugs with a known possibility of QTc prolongation (e. g. terfenadine, astemizole,

cisapride, pimozide, quinidine);

- Drugs whose plasma levels may be increased by voriconazole therapy (e. g.

sulfonylureas, ergot alkaloids, sirolimus, vinca alkaloids).

7. Subjects who have received the following drugs within 14 days prior to randomization: potent inducers of hepatic enzymes that will reduce voriconazole levels (e. g. rifampicin, carbamazepine and barbiturates)

8. Concomitant therapy with absorbable antifungals

9. Patient has a diagnosis of acute hepatitis or cirrhosis due to any cause

10. Known hypersensitivity or other contraindication to voriconazole

11. Patient is unwilling or unable to comply with the protocol.

12. Diseases or disabilities preventing the patient from participating in the trial

13. Females of childbearing potential without negative serum pregnancy test at baseline or within 72 hours prior to start of study drug

Klinikum der Universität Köln, Köln 50931, Germany

Johann Wolfgang Goethe-Universität Frankfurt am Main, Frankfurt am Main 60590, Germany

Universitätsklinikum Mannheim, Universität Heidelberg, Heidelberg 68305, Germany

Starting date: October 2004
Ending date: January 2006
Last updated: November 13, 2006