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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT01321372
First received: March 21, 2011
Last updated: March 18, 2013
Last verified: March 2013
  Purpose

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.


Condition
Acute Leukemia

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
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

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • To determine whether clinical responses (complete/partial/failure) directly correlate with patients' blood voriconazole levels. [ Time Frame: 4 years ] [ Designated as safety issue: No ]

    The primary outcome measure is defined by the following endpoints:

    1. abefrile for at least 48 hours
    2. no breakthrough fungal infection
    3. resolution or improvement of radiological findings


Secondary Outcome Measures:
  • The secondary objective of this study will focus on clinical toxicity, organ involvement and survival. [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    The secondary outcome of the study is defined as resolution of renal or hepatic dysfunction and survival.


Enrollment: 82
Study Start Date: June 2007
Study Completion Date: June 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Acute leukemia (including myelogenous and lymphocytic) patients for remission induction chemotherapy, reinduction chemotherapy and consolidation chemotherapy whose antifungal treatment includes voriconazole.

Criteria

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).
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01321372

Locations
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
University Health Network, Toronto
Investigators
Principal Investigator: Jack Seki, P.Ph, PharmD University Health Network, Toronto
  More Information

No publications provided

Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT01321372     History of Changes
Other Study ID Numbers: PMH-VOR
Study First Received: March 21, 2011
Last Updated: March 18, 2013
Health Authority: Canada: Ethics Review Committee

Additional relevant MeSH terms:
Leukemia
Neoplasms by Histologic Type
Neoplasms
Voriconazole
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 26, 2014