Fluconazole Compared With Voriconazole in Preventing Invasive Fungal Infections in Patients Undergoing Allogeneic Hematopoietic Transplantation
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on 2007-03-02
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Infection; Leukemia; Lymphoma; Myelodysplastic/Myeloproliferative Diseases
Intervention: fluconazole (Drug); voriconazole (Drug); antifungal therapy (Procedure); infection prophylaxis/management (Procedure); supportive care/therapy (Procedure)
Phase: Phase 3
Status: No longer recruiting. Expecting to enroll 600 people.
Sponsored by: Blood and Marrow Transplant Clinical Trials Network Official(s) and/or principal investigator(s):
John R. Wingard, MD, Study Chair, Affiliation: University of Florida Shands Cancer Center
Summary
RATIONALE: Antifungals, such as fluconazole and voriconazole, may be effective in preventing fungal infections in patients who are undergoing allogeneic peripheral stem cell or bone marrow transplantation. It is not yet known whether fluconazole is more effective than voriconazole in preventing fungal infections in patients who are undergoing allogeneic hematopoietic transplantation.
PURPOSE: This randomized phase III trial is studying fluconazole to see how well it works compared to voriconazole in preventing invasive fungal infections in patients who are undergoing an allogeneic hematopoietic transplant.
Clinical Details
Official title:
A Randomized Double-Blind Trial of Fluconazole vs. Voriconazole for the Prevention of Invasive Fungal Infections in Allogenic Blood and Marrow Transplant Patients
Study design: Interventional, Supportive Care, Randomized, Double-Blind, Active Control
Secondary outcome:
Detailed description:
OBJECTIVES:
Primary
* Compare the efficacy of fluconazole vs voriconazole in preventing fungal infections in patients undergoing allogeneic hematopoietic transplantation.
* Compare fungal-free survival rates at 180 days in patients treated with these regimens.
Secondary
* Compare invasive fungal infection rates in patients treated with these regimens.
* Compare overall mortality due to fungal infection in patients treated with these regimens.
* Compare engraftment rates and acute and chronic graft-versus-host disease rates in patients treated with these regimens.
* Compare reasons for failure (e. g., plasma concentrations, tolerance, or fungal sensitivity) in patients treated with these regimens.
* Compare the safety of these regimens in these patients.
OUTLINE: This is a randomized, double-blind, multicenter study. Patients are stratified according to participating center and donor type (sibling vs unrelated). Patients are randomized to 1 of 2 treatment arms.
* Arm I: Beginning on the day of transplantation, patients receive oral fluconazole once daily and oral placebo once daily on days 0-100*.
* Arm II: Beginning on the day of transplantation, patients receive oral voriconazole twice daily on days 0-100*.
NOTE: *Patients receiving ≥ 1 mg/kg/day of prednisone (or equivalent) between day 90 and 100 OR recipients of T-cell-depleted transplants receiving post-transplantation immunosuppression with a CD4 value < 200/µl between day 90 and 100 may continue to receive study drug until day 180.
On either arm, patients may receive study drug IV if oral administration is not possible.
In both arms, treatment continues in the absence of fungal infection or unacceptable toxicity.
Patients are followed for 1 year.
PROJECTED ACCRUAL: A total of 600 patients (300 per treatment arm) will be accrued for this study within 3 years.
Eligibility
Minimum age: 2 Years.
Gender(s): Both.
Criteria:
DISEASE CHARACTERISTICS:
* Diagnosis of 1 of the following:
- Acute myeloid leukemia
+ History of myelodysplastic syndromes (MDS) allowed
+ In first or second complete remission (less than 5% blasts) OR in early relapse (less than 30% blasts in bone marrow, no circulating blasts in peripheral blood, and no extramedullary disease)
- Acute lymphoblastic leukemia
+ In first or second complete remission (less than 5% blasts)
- Acute undifferentiated leukemia
+ In first or second complete remission (less than 5% blasts)
- Acute biphenotypic leukemia
+ In first or second complete remission (less than 5% blasts)
- Chronic myelogenous leukemia
+ Chronic or accelerated phase
- MDS of one of the following subtypes:
+ Refractory anemia (RA)
+ RA with ringed sideroblasts
+ Refractory cytopenia with multilineage dysplasia
+ Refractory cytopenia with multilineage dysplasia and ringed sideroblasts
+ RA with excess blasts (RAEB)-1 (5-10% blasts)
+ RAEB-2 (10-20% blasts)
+ MDS, unclassified
+ MDS associated with isolated del(5q)
+ Chronic myelomonocytic leukemia
- Lymphoma
+ Hodgkin's lymphoma
+ Chemosensitive disease AND receiving a related donor transplant
* Receiving an allogeneic peripheral blood or marrow transplantation from a family or unrelated donor OR receiving a cord blood transplantation from a sibling or other donor (for children under age 12)
- Must have a HLA 5/6 or 6/6 matched donor
* Receiving a myeloablative conditioning regimen
* No active CNS disease
PATIENT CHARACTERISTICS:
Age
* 2 and over
Performance status
* Karnofsky 70-100% OR
* Lansky 50-100% (for patients under age 16)
Life expectancy
* Not specified
Hematopoietic
* Not specified
Hepatic
* ALT ≤ 5 times upper limit or normal
* Bilirubin ≤ 2. 5 mg/dL
Renal
* Creatinine normal for age OR
* Creatinine clearance > 50% of lower limit of normal for age
Cardiovascular
* Asymptomatic*
* No prolonged QTc syndrome NOTE: *If symptomatic, must have LVEF > 40% at rest that improves with exercise OR shortening fraction > 26%
Pulmonary
* DLCO, FEV_1, and FVC > 45% of predicted OR
* Oxygen saturation > 85% on room air
Immunologic
* No history of allergy or intolerance to azoles (e. g., fluconazole, itraconazole, voriconazole, posaconazole, ketoconazole, miconazole, or clotrimazole)
* No invasive yeast infection within the past 8 weeks
- Colonized or superficial infection allowed
* No candidemia within the past 8 weeks
- Patients with candidemia more than 8 weeks prior to study entry must meet all of the following criteria:
+ Negative blood culture within the past 14 days
+ No clinical signs of candidemia
+ Not receiving antifungal therapy for candidemia
* No proven or probable aspergillus or other mold infection or deep mycoses (including hepatosplenic candidiasis) within the past 4 months
* No uncontrolled viral or bacterial infection
* HIV negative
Other
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No prior malignancy within the past 5 years except resected basal cell carcinoma or treated carcinoma in situ
- Cancer treated with curative intent > 5 years ago allowed
PRIOR CONCURRENT THERAPY:
Biologic therapy
* See Disease Characteristics
* No prior allogeneic or autologous transplantation
Chemotherapy
* Not specified
Endocrine therapy
* Not specified
Radiotherapy
* Not specified
Surgery
* Not specified
Other
* No more than 3 days of rifampin or carbamazepine treatment within the past 7 days
* No concurrent therapy with any of the following:
- Rifampin
- Rifabutin
- Carbamazepine
- Cisapride
- Terfenadine
- Astemizole
- Ergot alkaloids
- Long-acting barbiturates
- Sirolimus
- Quinidine
- Pimozide
- Dofetilide
- Nebulized or inhaled amphotericin
* No concurrent routine granulocyte transfusions
* No concurrent infection prophylaxis except for pneumocystis carinii, herpes viruses (HSV or VSV), or encapsulated bacteria
* No concurrent fungal prophylaxis during the conditioning regimen
* No other concurrent investigational drugs
Locations and Contacts
University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, Alabama 35294-0006, United States
City of Hope Comprehensive Cancer Center, Duarte, California 91010-3000, United States
Ida M. and Cecil H. Green Cancer Center at Scripps Clinic, La Jolla, California 92037-1027, United States
Moores UCSD Cancer Center, La Jolla, California 92093-0960, United States
Stanford Comprehensive Cancer Center at Stanford University Medical Center, Stanford, California 94305-5623, United States
Children's National Medical Center, Washington, District of Columbia 20010-2970, United States
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida, Tampa, Florida 33612-9497, United States
University of Florida Shands Cancer Center, Gainesville, Florida 32610-0232, United States
Children's Memorial Hospital - Chicago, Chicago, Illinois 60614, United States
Indiana University Cancer Center, Indianapolis, Indiana 46202-5289, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231-2410, United States
Children's Hospital Boston, Boston, Massachusetts 02115, United States
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston, Massachusetts 02115, United States
Barbara Ann Karmanos Cancer Institute, Detroit, Michigan 48201-1379, United States
University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48109-0942, United States
University of Minnesota Cancer Center, Minneapolis, Minnesota 55455, United States
Cardinal Glennon Children's Hospital, Saint Louis, Missouri 63104, United States
Children's Mercy Hospital, Kansas City, Missouri 64108, United States
Kansas City Cancer Centers - Central, Kansas City, Missouri 64111, United States
St. Louis Children's Hospital, Saint Louis, Missouri 63110, United States
UNMC Eppley Cancer Center at the University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, United States
Hackensack University Medical Center Cancer Center, Hackensack, New Jersey 07601, United States
Memorial Sloan-Kettering Cancer Center, New York, New York 10021, United States
Mount Sinai Medical Center, New York, New York 10029, United States
Roswell Park Cancer Institute, Buffalo, New York 14263-0001, United States
Duke Comprehensive Cancer Center, Durham, North Carolina 27710, United States
Wake Forest University Comprehensive Cancer Center, Winston-Salem, North Carolina 27157-1096, United States
Case Comprehensive Cancer Center, Cleveland, Ohio 44106-5065, United States
Oregon Health & Science University Cancer Institute, Portland, Oregon 97239-3098, United States
Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania 19104-4283, United States
M.D. Anderson Cancer Center at University of Texas, Houston, Texas 77030-4009, United States
Texas Transplant Institute, San Antonio, Texas 78229, United States
Virginia Commonwealth University Massey Cancer Center, Richmond, Virginia 23298-0037, United States
Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, United States
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date:
December 2003
Last updated: February 20, 2007
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