voriconazole with or without interferon gamma in treating patients with aspergillosis or other fungal infections

Conditions: Infection; Unspecified Adult Solid Tumor, Protocol Specific

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.

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 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

Keywords: infection unspecified adult solid tumor, protocol specific