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
2 Years
N/A
Both
Infection, Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
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
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Supportive Care
Principal Investigator
Thomas J. Walsh, MD
Investigator Role:
Study Chair
Investigator Affiliation:
National Cancer Institute (NCI)
Authority:
United States: Federal Government
Study ID:
CDR0000298887
NCT ID:
NCT00059878
Start Date:
August 2003
Completion Date:
January 2005
Related Keywords:
- Infection
- Unspecified Adult Solid Tumor, Protocol Specific
- infection
- unspecified adult solid tumor, protocol specific
- Aspergillosis
- Mycoses
Name | Location |
|---|---|
| Arkansas Cancer Research Center at University of Arkansas for Medical Sciences | Little Rock, Arkansas 72205 |
| Shands Cancer Center at the University of Florida Health Science Center | Gainesville, Florida 32610-0296 |
| Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support | Bethesda, Maryland 20892-1182 |
