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LymphomaPhase 3NCT00075803

Comparison of Fluconazole vs Voriconazole to Treat Fungal Infections for Blood and Marrow Transplants (BMT CTN 0101)

A Phase 3 study testing Fluconazole and Voriconazole in people with Lymphoma and Infection, run by Medical College of Wisconsin at 33 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 2 years and older
Conditions the study is for
Lymphoma, Infection, Leukemia
What is being tested?
Fluconazole and Voriconazole
Could I receive a placebo?
No, everyone receives an active treatment
How many people
600 participants
Where
33 sitesUnited States
Study dates
Nov 2003to Sep 2007
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Must receive an allogeneic peripheral blood or marrow transplant from a family or unrelated donor, or for children under the age of 12, a cord blood transplant from either a sibling or other donor
  • Must have a 5 or 6 of 6 human leukocyte antigens (HLA)-matched donor. The match may be determined at serologic level for HLA-A and HLA-B loci. 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:
  • Acute myelogenous leukemia (AML)
  • Acute lymphocytic leukemia (ALL)
  • Acute undifferentiated leukemia (AUL)
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  • Acute biphenotypic leukemia in first or second complete remission
  • Chronic myelogenous leukemia (CML) in either chronic or accelerated phase
  • One of the following myelodysplastic syndrome(s) (MDS):
  • Refractory anemia
  • Refractory anemia with ringed sideroblasts
  • Refractory cytopenia with multilineage dysplasia
  • Refractory cytopenia with multilineage dysplasia and ringed sideroblasts
  • Refractory anemia with excess blasts-1 (5-10% blasts)
  • Refractory anemia with excess blasts-2 (10-20% blasts)
  • MDS, unclassified
  • MDS associated with isolated del (5q)
  • Chronic myelomonocytic leukemia (CMML)
  • Lymphoma (including Hodgkin's) with chemosensitive disease (at least 50% response to chemotherapy) and receiving a related donor transplant
  • Receiving myeloablative conditioning regimens
  • Adequate physical function (cardiac, hepatic, renal, and pulmonary), within 6 weeks of initiation of conditioning (preferably within 4 weeks) unless otherwise specified
  • Baseline galactomannan blood samples drawn within 30 days prior to randomization with the results available prior to randomization (72 hours prior to transplant)
  • Chest computed tomography (CT) scans within 6 weeks prior to randomization if the results of the baseline galactomannan blood sample are not available prior to randomization (72 hours prior to transplant)

Who cannot join

  • Invasive yeast infection within the 8 weeks prior to conditioning regimen initiation. Patients are eligible if colonized or have had superficial infection. Patients with a history of candidemia greater than 8 weeks prior to conditioning must have a negative blood culture within 14 days of conditioning (within 7 days is recommended), no clinical signs of candidemia, and may not still require antifungal therapy
  • Presumptive, proven, or probable aspergillus or other mold infection or deep mycoses (including hepatosplenic candidiasis) within 4 months prior to conditioning regimen initiation
  • Uncontrolled viral or bacterial infection at the time of study registration
  • Pregnant or breastfeeding. Women of child-bearing age must avoid becoming pregnant while receiving antifungal agents
  • Karnofsky performance status less than 70% or Lansky status less than 50% for patients under 16 years old unless approved by the medical monitor or protocol chair
  • History of allergy or intolerance to azoles (e.g., fluconazole, itraconazole, voriconazole, posaconazole, ketoconazole, miconazole, clotrimazole)
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  • Requiring therapy with rifampin, rifabutin, carbamazepine, cisapride (Propulsid®), terfenadine (Seldane®), astemizole (Hismanal®), ergot alkaloids, long-acting barbiturates, or who have received more than 3 days treatment with rifampin or carbamazepine within 7 days prior to conditioning regimen initiation. Patients on therapeutic anticoagulation with coumadin (1 mg/day for port prophylaxis is permitted)
  • Receiving sirolimus
  • Prolonged QTc syndrome at study entry
  • HIV positive
  • Receiving another investigational drug unless cleared by the medical monitors
  • Received a prior allogeneic or autologous transplant
  • Active central nervous system disease
  • On fungal prophylaxis during conditioning regimen (it is recommended that fungal prophylaxis be suspended once patient is enrolled)
  • Prior cancer, other than resected basal cell carcinoma or treated carcinoma in-situ. Cancer treated with curative intent less than 5 years previously will not be allowed unless approved by the medical monitor or protocol chair. Cancer previously treated with curative intent over 5 years ago will be allowed

Trial locations and contacts

33 sites in 1 country.

33 sites in 1 country

United States33 sites
  • University of Michigan Medical Center

    Ann Arbor, Michigan, 48109

  • Johns Hopkins/SKCCC

    Baltimore, Maryland, 21231

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Dana Farber Cancer Institute/Brigham & Womens

    Boston, Massachusetts, 02114

  • Dana Farber Cancer Institute/Children's Hospital of Boston

    Boston, Massachusetts, 02114

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Ann & Robert H. Lurie Children's Hospital of Chicago

    Chicago, Illinois, 60614

  • University Hospitals of Cleveland/Case Western

    Cleveland, Ohio, 44106

  • Karmanos Cancer Institute/BMT

    Detroit, Michigan, 48201

  • Duke University Medical Center

    Durham, North Carolina, 27705

  • University of Florida College of Medicine (Shands)

    Gainesville, Florida, 32610

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • University of Texas/MD Anderson CRC

    Houston, Texas, 77030

  • Indiana University Medical Center

    Indianapolis, Indiana, 46202

  • Children's Mercy Hospitals and Clinics

    Kansas City, Missouri, 64108

  • Kansas City Cancer Centers

    Kansas City, Missouri, 64111

  • UCSD Medical Center

    La Jolla, California, 92093

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10021

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • University of Pennsylvania Cancer Center

    Philadelphia, Pennsylvania, 19104

  • Oregon Health Sciences University

    Portland, Oregon, 97239

  • Utah BMT/Univ of Utah Med School

    Salt Lake City, Utah, 84132

  • Texas Transplant Institute

    San Antonio, Texas, 78229

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

  • Cardinal Glennon Children's Hospital

    St Louis, Missouri, 63110

  • Washington University/Barnes Jewish Hospital

    St Louis, Missouri, 63110

  • Washington University/St. Louis Children's Hospital

    St Louis, Missouri, 63110

  • Stanford Hospital and Clinics

    Stanford, California, 94305

  • H. Lee Moffitt Cancer Center

    Tampa, Florida, 33624

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this 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)

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.

Read the detailed description

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.

Being tested
Fluconazole, Voriconazole
Keywords
Myelodysplastic and Myeloproliferative Diseases
Medical subject headings
Lymphoma, Infections, Leukemia, Myelodysplastic-Myeloproliferative Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FluconazoleDrug

    Also called Diflucan

    Fluconazole will be administered orally once daily. Fluconazole capsules should be taken at least one hour before or one hour after a meal. If oral drug is not possible, it will be given intravenously once daily in a total volume of 200 mL in patients > 12 years. For adults, each 200 mL infusion will be administered over 2 hours. In patients < 12 years, intravenous doses will be prepared.

  • VoriconazoleDrug

    Also called Vfend

    Voriconazole will be administered orally twice daily. Voriconazole capsules should be taken at least one hour before or one hour after a meal. Taken concomitantly with food, bioavailability of voriconazole is reduced. If oral drug is not possible, it will be given intravenously at a dosage of 200 mg every 12 hours over two hours in patients > 12 years. Each voriconazole dose will be diluted to a total volume of 200 mL in patients > 12 years. Volumes of the formulation required to provide 4 mg/kg doses for children age < 12 years.

Study groups in NCT00075803
Study groupRoleWhat they receive
FluconazoleActive comparatorThe dose of fluconazole is 400 mg by mouth or intravenous drip.
Receives: Drug: Fluconazole
VoriconazoleExperimentalThe dose of oral voriconazole is 200 mg twice daily. When voriconazole must be given intravenously, it will be given at a dose of 200 mg every 12 hours for the duration of intravenous therapy.
Receives: Drug: Voriconazole

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Fungal-free Survival (Percentage of Participants Alive and Free From Proven, Probable, or Presumptive Invasive Fungal Infection) at 180 Days Post-transplant

    Measured: 180 days

Secondary outcomes (12)
  1. Frequency of Invasive Fungal Infections (IFI)

    Incidence of proven, probably, or presumptive IFI

    Measured: 1 year

  2. Percentage of Patients With Invasive Fungal Infection at 100, 180, and 365 Days

    Measured: 100, 180, and 365 days

  3. Overall Survival

    Measured: 100, 180, and 365 days

  4. Relapse Free Survival

    Measured: 100, 180, and 365 days

  5. Frequency of Use of Amphotericin B or Caspofungin

    Measured: 1 year

  6. Duration of Use of Amphotericin B or Caspofungin

    Measured: 180 days

  7. Time to and Severity of Acute and Chronic Graft vs Host Disease (GVHD)

    Measured: 100 and 365 days

  8. Utility of Galactomannan Assay in Diagnosis of Aspergillus and Response to Therapy

    Although there were 82 Galactomannan (GM) positives, 4 were excluded due to piperacillin/tazobactam administration, without other documentation of IFI, and were deemed false positives.

    Measured: 1 year

  9. Time to Neutrophil Engraftment

    Measured: 28 days

  10. Time to Platelet Engraftment

    Measured: 180 days

  11. Failure to Engraft

    Measured: day 42

  12. Freedom From Possible, Presumptive, Probable, or Proven Invasive Fungal Infection, Death, or Withdrawal of Study Drug Due to Toxicity, Intolerance, or an Empirical Trial of Amphotericin B or Caspofungin Greater Than 14 Consecutive Days

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jan 2004 (estimated)
  2. Study startNov 2003
  3. Primary completionSep 2006
  4. Study completionSep 2007

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
600 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00075803
Sponsor's protocol ID
BMTCTN0101
Other IDs
BMT CTN 0101, U01HL069294, 5U24CA076518
Status last verified
Dec 2022
First submitted
9 Jan 2004
Last updated
4 Jan 2023
Data monitoring committee
Yes
Individual data sharing
Yes

Publications

  • Wingard JR, Carter SL, Walsh TJ, Kurtzberg J, Small TN, Baden LR, Gersten ID, Mendizabal AM, Leather HL, Confer DL, Maziarz RT, Stadtmauer EA, Bolanos-Meade J, Brown J, Dipersio JF, Boeckh M, Marr KA; Blood and Marrow Transplant Clinical Trials Network. Randomized, double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation. Blood. 2010 Dec 9;116(24):5111-8. doi: 10.1182/blood-2010-02-268151. Epub 2010 Sep 8.

    PubMed 20826719
  • Mauskopf J, Chirila C, Graham J, Gersten ID, Leather H, Maziarz RT, Baden LR, Bolanos-Meade J, Brown JM, Walsh TJ, Horowitz MH, Kurtzberg J, Marr KA, Wingard JR. Comparative cost-effectiveness analysis of voriconazole and fluconazole for prevention of invasive fungal infection in patients receiving allogeneic hematopoietic cell transplants. Am J Health Syst Pharm. 2013 Sep 1;70(17):1518-27. doi: 10.2146/ajhp120599.

    PubMed 23943184

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Fluconazole and Voriconazole in people with Lymphoma and Infection, run by Medical College of Wisconsin at 33 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Sep 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Fungal-free Survival (Percentage of Participants Alive and Free From Proven, Probable, or Presumptive Invasive Fungal Infection) at 180 Days Post-transplant (time frame: 180 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00075803, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jan 2023.

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