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

Study Overview
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Brief Summary
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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
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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

Conditions
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Leukemia, Myelocytic, Acute

Intervention / Treatment
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* Drug: voriconazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed or relapsed, de novo or secondary AML First induction chemotherapy cycle Expected neutropenic phase of a minimum duration of 10 days Age >= 18 years Legally signed consent form Exclusion Criteria: Known proven, probable or possible invasive fungal infection at randomization or in patient history 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) Any current fever unless explained by non-infectious causes Antibacterial prophylaxis other than TMP/SMX Liver function test [LFT] (AST/ALT/bilirubin) more than 3x the upper normal limit 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). 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) Concomitant therapy with absorbable antifungals Patient has a diagnosis of acute hepatitis or cirrhosis due to any cause Known hypersensitivity or other contraindication to voriconazole Patient is unwilling or unable to comply with the protocol. Diseases or disabilities preventing the patient from participating in the trial Females of childbearing potential without negative serum pregnancy test at baseline or within 72 hours prior to start of study drug

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: voriconazole|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  |  |