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

Leukemia, Myelocytic, Acute Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00152594
• Other study ID #: NRA 150 0009
• Status: Terminated
• Phase: Phase 3
• First received: September 7, 2005
• Last updated: November 13, 2006
• Start date: October 2004
• Est. completion date: January 2006

Study information

• Verified date: November 2006
• Source: University of Cologne
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 150
• Est. completion date: January 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myelocytic, Acute
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• voriconazole

Locations

Country	Name	City	State
Germany	Johann Wolfgang Goethe-Universität Frankfurt am Main	Frankfurt am Main
Germany	Universitätsklinikum Mannheim, Universität Heidelberg	Heidelberg
Germany	Klinikum der Universität Köln	Köln

Sponsors (1)

Lead Sponsor	Collaborator
University of Cologne

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	To determine and compare between study arms the: incidence of fever and other signs of infection
Secondary	incidence and type of documented bacteremia
Secondary	rate of patients with systemic open-label antifungal therapy
Secondary	time to initiation of systemic open-label antifungal therapy
Secondary	duration of absolute neutrophil count < 500/µl
Secondary	rate and type of proven, probable and possible breakthrough invasive fungal infections
Secondary	rate of patients with fever of unknown origin
Secondary	incidence and severity of adverse events
Secondary	trough voriconazole plasma level after day 8 of study treatment
Secondary	direct costs of systemic antibiotics, antifungals and antivirals and diagnostic imaging
Secondary	overall costs in terms of the diagnosis related groups applied to the study patients