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

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00059878

Collaborator

(none)

Locations

17.1

Duration (Months)

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Infection Unspecified Adult Solid Tumor, Protocol Specific	Biological: recombinant interferon gamma Drug: voriconazole	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Masking:

Double

Primary Purpose:

Supportive Care

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

Study Start Date :

Aug 1, 2003

Actual Study Completion Date :

Jan 1, 2005

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
2	Shands Cancer Center at the University of Florida Health Science Center	Gainesville	Florida	United States	32610-100277
3	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland	United States	20892-1182