Voriconazole With or Without Interferon Gamma in Treating Patients With Aspergillosis or Other Fungal Infections - Full Text View

Sponsor:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00059878

Purpose

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	Intervention	Phase
Infection Unspecified Adult Solid Tumor, Protocol Specific	Biological: recombinant interferon gamma Drug: voriconazole	Phase II

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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Fungal Infections Molds

Drug Information available for: Interferon gamma-1b Voriconazole Interferons

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:

August 2003

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.

Eligibility

Ages Eligible for Study:	2 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00059878

Locations

United States, Arkansas
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, Florida
Shands Cancer Center at the University of Florida Health Science Center
Gainesville, Florida, United States, 32610-100277
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Study Chair:

Thomas J. Walsh, MD

NCI - Pediatric Oncology Branch

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000298887, NCI-03-C-0111
Study First Received:	May 6, 2003
Last Updated:	May 9, 2009
ClinicalTrials.gov Identifier:	NCT00059878 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

infection
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:

Communicable Diseases
Anti-Infective Agents
Interferon Type II
Antineoplastic Agents
Interferons
Aspergillosis
Infection

Antiviral Agents
Pharmacologic Actions
Mycoses
Antifungal Agents
Therapeutic Uses
Voriconazole
Interferon-gamma, Recombinant

ClinicalTrials.gov processed this record on November 27, 2009