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

Acute Leukemia Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01321372
• Other study ID #: PMH-VOR
• Status: Completed
• Phase: N/A
• First received: March 21, 2011
• Last updated: March 18, 2013
• Start date: June 2007
• Est. completion date: June 2011

Study information

• Verified date: March 2013
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Ethics Review Committee
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: June 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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).

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Acute Leukemia

Locations

Country	Name	City	State
Canada	Princess Margaret Hospital	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine whether clinical responses (complete/partial/failure) directly correlate with patients' blood voriconazole levels.	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	4 years	No
Secondary	The secondary objective of this study will focus on clinical toxicity, organ involvement and survival.	The secondary outcome of the study is defined as resolution of renal or hepatic dysfunction and survival.	4 years	No