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Sponsors and Collaborators: |
National Heart, Lung, and Blood Institute (NHLBI) Blood and Marrow Transplant Clinical Trials Network National Cancer Institute (NCI) |
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Information provided by: | National Heart, Lung, and Blood Institute (NHLBI) |
ClinicalTrials.gov Identifier: | NCT00075803 |
The study is designed as a Phase III, randomized, double-blind, multicenter, prospective, comparative study of fluconazole versus voriconazole for the prevention of fungal infections in allogeneic transplant recipients. Recipients will be stratified by center and donor type (sibling vs. unrelated) and will be randomized to either the fluconazole or voriconazole arm in a 1:1 ratio.
Condition | Intervention | Phase |
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Lymphoma Infection Leukemia |
Drug: Fluconazole Drug: Voriconazole |
Phase III |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double Blind (Subject, Investigator), Parallel Assignment, Efficacy Study |
Official Title: | 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) |
Enrollment: | 600 |
Study Start Date: | November 2003 |
Study Completion Date: | September 2007 |
Primary Completion Date: | September 2006 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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1: Active Comparator
fluconazole
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Drug: Fluconazole
Age Drug Route Renal Function Dosage Adult fluconazole PO normal 400 mg/d voriconazole PO normal 200 mgQ12H Adult * fluconazole PO < 50 mg/min 200 mg/d voriconazole PO < 50 mg/min 200 mgQ12H Age < 12 and > 20 kg fluconazole PO normal 200 mg/d voriconazole PO normal 100 mgQ12H Age < 12 and > 20 kg * fluconazole PO < 50 mg/min 100 mg/d voriconazole PO < 50 mg/min 100 mgQ12H Age < 12 and < 20 kg fluconazole PO normal 100 mg/d voriconazole PO normal 50 mgQ12H
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2: Experimental
voriconazole
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Drug: Voriconazole
Age Drug Route Renal Function Dosage Adult fluconazole PO normal 400 mg/d voriconazole PO normal 200 mgQ12H Adult * fluconazole PO < 50 mg/min 200 mg/d voriconazole PO < 50 mg/min 200 mgQ12H Age < 12 and > 20 kg fluconazole PO normal 200 mg/d voriconazole PO normal 100 mgQ12H Age < 12 and > 20 kg * fluconazole PO < 50 mg/min 100 mg/d voriconazole PO < 50 mg/min 100 mgQ12H Age < 12 and < 20 kg fluconazole PO normal 100 mg/d voriconazole PO normal 50 mgQ12H
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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.
Ages Eligible for Study: | 2 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
For sibling donors, matching may be determined at serologic level for HLA-DR; for unrelated donors, matching for HLA-DRB1 must be at the high-resolution molecular level
Must have one of the following underlying diseases:
One of the following myelodysplastic syndrome(s) (MDS):
Exclusion Criteria:
Principal Investigator: | Donna Salzman, MD | University of Alabama at Birmingham |
Principal Investigator: | Jeffrey Andrey, MD | Scripps Cancer Center |
Principal Investigator: | Janice Brown, MD | Stanford Hospital and Clinics |
Principal Investigator: | Edward Ball, MD | UCSD Medical Center |
Principal Investigator: | Naynesh Kamani, MD | Children's Research Institute |
Principal Investigator: | Claudio Anasetti, MD | H. Lee Moffitt Cancer Center |
Study Chair: | John Wingard, MD | University of Florida College of Medicine (Shands) |
Principal Investigator: | Reggie Duerst, MD | Children's Memorial - Northwestern |
Principal Investigator: | Paul Haut, MD | Indiana University School of Medicine |
Principal Investigator: | Lindsey Robert Baden, MD | Dana Farber Cancer Institute/Brigham & Womens |
Principal Investigator: | Leslie Lehmann, MD | Dana Farber Cancer Institute/Children's Hospital of Boston |
Principal Investigator: | Richard Jones, MD | Johns Hopkins/SKCCC |
Principal Investigator: | Voravit Ratanatharathorn, MD | Karmanos Cancer Institute/BMT |
Principal Investigator: | Choon-Kee Lee, MD | University of Michigan |
Principal Investigator: | Jo-Anne van Burik, MD | University of Minnesota |
Principal Investigator: | William Ferguson, MD | Cardinal Glennon Children's Hospital |
Principal Investigator: | Alan Gamis, MD | Children's Mercy Hospital Kansas City |
Principal Investigator: | Joseph McGuirk, MD | Kansas City Cancer Centers |
Principal Investigator: | John DiPersio, MD | Washington University/Barnes Jewish Hospital |
Principal Investigator: | Shalini Shenoy, MD | Washington University/St. Louis Children's Hospital |
Principal Investigator: | Joanne Kurtzberg, MD | Duke University |
Principal Investigator: | Kevin High, MD | Wake Forest University |
Principal Investigator: | Marcel Devetten, MD | University of Nebraska |
Principal Investigator: | Scott Rowley, MD | Hackensack University Medical Center |
Principal Investigator: | Joel Brochstein, MD | Hackensack University Medical Center |
Principal Investigator: | Trudy Small, MD | Memorial Sloan-Kettering Cancer Center |
Principal Investigator: | Brahm Segal, MD | Roswell Park Cancer Institute |
Principal Investigator: | Hillard Lazarus, MD | University Hospitals of Cleveland/Case Western |
Principal Investigator: | Richard Maziarz, MD | Oregon Health and Science University |
Principal Investigator: | H. Stacy Nicholson, MD | Oregon Health and Science University |
Principal Investigator: | Nancy Bunin, MD | Children's Hospital of Philadelphia |
Principal Investigator: | Edward Stadtmauer, MD | University of Pennsylvania |
Principal Investigator: | Paul Shaughnessy, MD | Texas Transplant Institute |
Principal Investigator: | Michael Grimley, MD | Texas Transplant Institute |
Principal Investigator: | Sergio Giralt, MD | University of Texas/MD Anderson CRC |
Principal Investigator: | Michael Pulsipher, MD | Utah BMT/Primary Children's Medical Center |
Principal Investigator: | Kieren Marr, MD | Fred Hutchinson Cancer Research Center |
Study ID Numbers: | 416, BMTCTN-0101, UF-G-074-2003, FHCRC-1808.00, CDR0000349374, U01 HL069294 |
Study First Received: | January 9, 2004 |
Last Updated: | August 20, 2008 |
ClinicalTrials.gov Identifier: | NCT00075803 History of Changes |
Health Authority: | United States: Federal Government; United States: Food and Drug Administration |
Myelodysplastic and Myeloproliferative Diseases |
Fluconazole Immunoproliferative Disorders Clotrimazole Miconazole Myeloproliferative Disorders Tioconazole Mycoses |
Leukemia Lymphatic Diseases Antifungal Agents Voriconazole Lymphoproliferative Disorders Lymphoma |
Fluconazole Anti-Infective Agents Communicable Diseases Neoplasms by Histologic Type Immunoproliferative Disorders Immune System Diseases Infection Pharmacologic Actions Leukemia |
Mycoses Lymphatic Diseases Neoplasms Therapeutic Uses Antifungal Agents Voriconazole Lymphoproliferative Disorders Lymphoma |