Voriconazole With or Without Interferon Gamma in Treating Patients With Aspergillosis or Other Fungal Infections
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Infection; Unspecified Adult Solid Tumor, Protocol Specific
Intervention: recombinant interferon gamma (Drug); voriconazole (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: National Cancer Institute (NCI) Official(s) and/or principal investigator(s):
Thomas J. Walsh, MD, Study Chair, Affiliation: NCI - Pediatric Oncology Branch
Summary
RATIONALE: Antifungals such as voriconazole may be effective in controlling fungal
infections. Combining voriconazole with interferon gamma may be more effective than
voriconazole alone in treating fungal infections.
PURPOSE: Randomized phase II trial to compare the effectiveness of voriconazole with or
without interferon gamma in treating patients who have aspergillosis or other fungal
infections.
Clinical Details
Official title: A Prospective, Randomized, Double-Blind, Multicenter Pilot Study Of The Safety And Efficacy Of Interferon Gamma- 1b (IFN-y 1b) Plus Voriconazole Versus Placebo Plus Voriconazole In The Treatment Of Invasive Aspergillosis And Other Filamentous Fungal Infections
Study design: Supportive Care, Randomized, Double-Blind, Active Control
Detailed description:
OBJECTIVES:
- Determine the safety profile of voriconazole and interferon gamma in patients with
invasive aspergillosis or other filamentous fungal infections.
- Compare the efficacy and possible heterogeneity in efficacy of voriconazole with or
without interferon gamma across different patient sub-populations, in terms of designing
a larger phase II or pivotal phase III study.
- Determine the time to partial or complete response and rate of response (at weeks 6 and
12 or at end of treatment and follow-up) in patients receiving interferon gamma.
- Compare the proportion of patients with at least a two-fold reduction in the
galactomannan antigenemia titer at 6 and 12 weeks or at end of treatment with these
regimens.
- Determine surrogate immunologic markers for response to interferon gamma, functional
integrity and anti-fungal activity of phagocytic cells (neutrophils, monocytes, and
macrophages), and nonphagocytic effector cells (natural killer and T cells) in these
patients.
OUTLINE: This is a randomized, double-blind, multicenter, pilot study. Patients are
stratified according to age (under 18 vs 18 and over) and absolute neutrophil count (less
than 500/mm^3 vs at least 500/mm^3). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive voriconazole (IV over 80-120 minutes for the first 3 doses and
orally every 12 hours for subsequent doses) 3 times per week and interferon gamma
subcutaneously (SC) 3 times per week.
- Arm II: Patients receive voriconazole as in arm I and placebo SC 3 times per week.
In both arms, treatment continues for 12 weeks in the absence of disease progression or
unacceptable toxicity.
Patients are followed at 4 weeks.
PROJECTED ACCRUAL: A total of 88 patients (44 per treatment arm) will be accrued for this
study.
Eligibility
Minimum age: 2 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
DISEASE CHARACTERISTICS:
- Proven or probable invasive aspergillosis or other filamentous fungal infection by
cytology, histopathology, or culture within the past 7 days
- Presenting with 1 of the following:
- Cancer
- Aplastic anemia
- Inherited immunodeficiencies
- Autoimmune deficiency disorders
- Acquired immunodeficiencies
- Recipient of autologous peripheral blood stem cell or bone marrow
transplantation
- CNS aspergillosis or other filamentous fungal infection allowed
- No invasive zygomycosis infection
PATIENT CHARACTERISTICS:
Age
- 2 and over
Performance status
- Not specified
Life expectancy
- At least 7 days
Hematopoietic
- Not specified
Hepatic
- ALT no greater than 5 times upper limit of normal
Renal
- Creatinine clearance at least 30 mL/min
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective barrier contraception
- No prior significant CNS disorder (e. g., multiple sclerosis or uncontrolled seizures)
- No prior grade 3 or 4 toxicity or severe allergic reaction to interferon gamma
- No prior intolerance or hypersensitivity to voriconazole or other azoles
- No acute or chronic graft-versus-host disease
- No conditions that would preclude study compliance
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
- No prior allogeneic peripheral blood or bone marrow transplantation
- No concurrent interferon alfa
Chemotherapy
- Not specified
Endocrine therapy
- Not specified
Radiotherapy
- Not specified
Surgery
- No prior solid organ transplantation
Other
- Prior voriconazole allowed
- At least 24 hours since prior administration of any of the following:
- Astemizole
- Cisapride
- Pimozide
- Quinidine
- Sirolimus
- Terfenadine
- Rifabutin
- Ergot alkaloids
- Sildenafil citrate
- Amiodarone
- Flecainide
- Systemic lidocaine
- More than 14 days since prior long-acting barbiturates, carbamazepine, or rifampin
- No other concurrent systemic antifungal drugs
- No other concurrent investigational agents
Locations and Contacts
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, United States
Shands Cancer Center at the University of Florida Health Science Center, Gainesville, Florida 32610-100277, United States
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support, Bethesda, Maryland 20892-1182, United States
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: August 2003
Last updated: May 23, 2008
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