A Randomized Double-blind Trial of Fluconazole Versus Voriconazole for the Prevention of Invasive Fungal Infections in Allogeneic Blood and Marrow Transplant Patients (BMT CTN #0101)
BACKGROUND:
Allogeneic blood and marrow transplant patients are highly susceptible to invasive fungal
infection prior to engraftment, due to neutropenia and mucosal injury. After engraftment,
an impairment of cell mediated immunity from graft-versus-host disease (GVHD) and the use of
aggressive immunosuppressive therapies, such as corticosteroids, leave patients vulnerable
to invasive fungal infections. Recipients of alternate donor transplants are especially
susceptible due to slow reconstitution of cell mediated immunity.
Fluconazole prophylaxis in prospective randomized trials of both autologous and allogeneic
transplant recipients has been demonstrated to reduce invasive fungal infections due to
yeasts prior to engraftment. A prolonged course of fluconazole given during the first 75
days (to cover the early post-engraftment period of risk) is highly effective in the
prevention of early and later yeast infections. This has translated into a survival
benefit. A recent analysis of long-term outcomes of these individuals demonstrated a
continuing benefit beyond the course of prophylaxis with a further benefit in survival. In
another study of various factors associated with survival after matched unrelated donor
transplants, fluconazole prophylaxis was an independent predictor for overall survival in a
multivariate analysis. Fluconazole prophylaxis has been found to be effective and safe with
few substantive drug interactions and has been widely adopted by transplant clinicians.
DESIGN NARRATIVE:
This is a randomized, double-blind, multicenter, prospective, comparative study of
fluconazole versus voriconazole for the prevention of fungal infections in allogeneic
hematopoietic transplant recipients and cord blood recipients in children under the age of
12. Prior to the start of the pre-transplant conditioning regimen, participants will give
written informed consent and be screened for eligibility. Participants who meet all entry
criteria will be assigned randomly to voriconazole or fluconazole within 72 hours of Day 0.
Participants will begin the study drug on Day 0 (after completion of the conditioning
regimen). Day 0 is defined as the day infusion of the stem cell product is completed. The
study drug will be continued until Day 100 following transplant or until one or more
criteria for early withdrawal are met. Continuation of the study drug beyond Day 100 is
permitted for participants who meet specific criteria. The development of any fungal
infection during prophylaxis will be classified according to the definitions listed in the
protocol.
Interventional
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Fungal-free survival (proportion of participants alive and free from proven, probable, or presumptive invasive fungal infection) at 180 days post-transplant
180 days
Donna Salzman, MD
Principal Investigator
University of Alabama at Birmingham
United States: Federal Government
416
NCT00075803
November 2003
September 2007
Name | Location |
---|---|
Roswell Park Cancer Institute | Buffalo, New York 14263 |
Fred Hutchinson Cancer Research Center | Seattle, Washington 98109 |
Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
Children's Hospital of Philadelphia | Philadelphia, Pennsylvania 19104 |
University of Pennsylvania Cancer Center | Philadelphia, Pennsylvania 19104 |
University of Nebraska Medical Center | Omaha, Nebraska 68198-3330 |
Hackensack University Medical Center | Hackensack, New Jersey 07601 |
Children's National Medical Center | Washington, District of Columbia 20010-2970 |
Cardinal Glennon Children's Hospital | Saint Louis, Missouri 63104 |
University of Minnesota | Minneapolis, Minnesota 55455 |
University of Alabama at Birmingham | Birmingham, Alabama 35294-3300 |
Duke University Medical Center | Durham, North Carolina 27710 |
University of Michigan Medical Center | Ann Arbor, Michigan 48104-0914 |
Oregon Health Sciences University | Portland, Oregon |
Scripps Cancer Center | La Jolla, California 92037 |
H. Lee Moffitt Cancer Center | Tampa, Florida 33612 |
Indiana University Medical Center | Indianapolis, Indiana 46202 |
Texas Transplant Institute | San Antonio, Texas 78229 |
UCSD Medical Center | La Jolla, California 92093 |
Stanford Hospital and Clinics | Stanford, California 94305 |
University of Florida College of Medicine (Shands) | Gainesville, Florida 32610 |
Children's Memorial - Northwestern | Chicago, Illinois 60614 |
Johns Hopkins/SKCCC | Baltimore, Maryland 21231 |
Dana Farber Cancer Institute/Brigham & Womens | Boston, Massachusetts 02114 |
Dana Farber Cancer Institute/Children's Hospital of Boston | Boston, Massachusetts 02114 |
Karmanos Cancer Institute/BMT | Detroit, Michigan 48201 |
Kansas City Cancer Centers | Kansas City, Missouri 64111 |
Children's Mercy Hospitals and Clinics | Kansas City, Missouri 64108 |
Washington University/Barnes Jewish Hospital | St. Louis, Missouri 63110 |
Washington University/St. Louis Children's Hospital | St. Louis, Missouri 63110 |
Wake Forest University Health Sciences | Winston-Salem, North Carolina 27157 |
University Hospitals of Cleveland/Case Western | Cleveland, Ohio 44106 |
University of Texas/MD Anderson CRC | Houston, Texas 77030 |
Utah BMT/Primary Children's Medical Center | Salt Lake City, Utah 84132 |