Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Supportive care	Completed	2 and over	NCI	NCI-03-C-0111 NCT00059878

Objectives

1. Determine the safety profile of voriconazole and interferon gamma in patients with invasive aspergillosis or other filamentous fungal infections.
2. 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.
3. 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.
4. 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.
5. 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.

Entry 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

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

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

Expected Enrollment

A total of 88 patients (44 per treatment arm) will be accrued for this study.

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/mm³ vs at least 500/mm³). 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.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Thomas Walsh, MD, Protocol chair		Ph: 301-402-0023

Registry Information
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
Trial Start Date		2003-08-08
Registered in ClinicalTrials.gov		NCT00059878
Date Submitted to PDQ		2003-03-12
Information Last Verified		2004-07-09

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