An Observational Analysis of Voriconazole Therapeutic Drug Concentration Monitoring, Pharmacogenomics and Clinical Outcome Correlations in High-risk Hematology Patients

Hematology patients are at high risk for invasive fungal infection (IFI) and are being treated with voriconazole (VOR) at Princess Margaret Hospital (PMH). It is critical that patients' serum drug levels are within therapeutic ranges when undergoing treatment. The primary objective of this study is to determine whether clinical responses (complete/partial/failure) directly correlate with patients' blood VOR drug levels.

In patients whose disease progression is associated with inadequate voriconazole (VOR) drug levels, serum drug level determination can allow for dose adjustment, thereby preventing disease progression. Patients who are extensive metabolizers may have subtherapeutic VOR levels leading to treatment failure whereas, poor metabolizers may have high drug levels that cause toxicity. Isoenzyme such as CYP2C19 exhibits genetic polymorphism. Genotyping tests can also be helpful in determining patient risk subjecting to extreme spectrum of drug levels.

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Key information

Conditions

Acute Leukemia

Sex eligibility

All sexes

Study type

Observational

Primary location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Acute leukemia (including myelogenous and lymphocytic) patients for remission induction chemotherapy, reinduction chemotherapy and consolidation chemotherapy whose antifungal treatment include voriconazole.
Patients have been subscribed voriconazole for probable or proven fungal infections by microbiological/cytohistological evidence from fine needle aspirate or bronchoalveolarlavage means.
Patients will also have imaging positive from lose dose CT results depicting halo signs or crescent signs suggestive of invasive fungal infections.
Patients must be able to tolerate oral intake of medications.

Exclusion criteria

Patients unable to tolerate oral administration with any combinations of severe mucositis (> or = grade 3), nausea/vomiting (> or = grade 3), diarrhea (> or =grade 2), neutropenic enterocolitis (> or = grade3).

Treatment and study plan

Primary outcomes

To determine whether clinical responses (complete/partial/failure) directly correlate with patients' blood voriconazole levels.

Time frame: 4 years
The primary outcome measure is defined by the following endpoints:
- abefrile for at least 48 hours
- no breakthrough fungal infection
- resolution or improvement of radiological findings

Secondary outcomes

The secondary objective of this study will focus on clinical toxicity, organ involvement and survival.

Time frame: 4 years

The secondary outcome of the study is defined as resolution of renal or hepatic dysfunction and survival.

Sponsors and collaborators

Lead sponsor

University Health Network, Toronto

Other

Registry information

Official study title

A Prospective, Observational Analysis of Voriconazole (VOR) Therapeutic Drug Concentration Monitoring, Pharmacogenomics and Clinical Outcome Correlations in High-risk Hematology Patients at Princess Margaret Hospital

Important dates

Study start: 2007
Primary completion: 2011
Study completion: 2011
First posted: Mar 23, 2011
Registry last updated: Mar 19, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

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