Voriconazole With or Without Interferon Gamma in Treating Patients With Aspergillosis or Other Fungal Infections

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Infection, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Biological: recombinant interferon gamma
* Drug: voriconazole


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: recombinant interferon gamma|nan|
|Drug: voriconazole|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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infection, unspecified adult solid tumor, protocol specific