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”

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.

Study Type: Interventional

Study Design: Supportive Care, Randomized, Double-Blind, Active Control

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.

Intervention(s) in this Clinical Trial

• Drug: recombinant interferon gamma
• Drug: voriconazole

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 2 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Cancer Institute (NCI)

Overall Clinical Trial Officials and Contacts

Thomas J. Walsh, MD Study Chair NCI - Pediatric Oncology Branch  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00059878

Study ID Number: CDR0000298887

ClinicalTrials.gov Identifier: NCT00059878

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database