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: Randomized phase III trial to compare the effectiveness of fluconazole with that of voriconazole in preventing invasive fungal infections in patients who are undergoing allogeneic hematopoietic transplantation.

Condition	Treatment or Intervention	Phase
childhood non-Hodgkin's lymphoma Infection Leukemia Lymphoma myelodysplastic and myeloproliferative diseases	Drug: fluconazole  Drug: voriconazole  Procedure: antifungal therapy  Procedure: infection prophylaxis/management  Procedure: supportive care/therapy	Phase III

Further Study Details: 

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*.
• 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.

Ages Eligible for Study:  2 Years and above,  Genders Eligible for Study:  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)
• 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
• , 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

Alabama
      University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham,  Alabama,  35294-3300,  United States; Recruiting
California
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States; Recruiting
      Rebecca and John Moores UCSD Cancer Center, La Jolla,  California,  92037-0960,  United States; Recruiting
      Scripps Cancer Center at Scripps Clinic, La Jolla,  California,  92037-1027,  United States; Recruiting
      Stanford Cancer Center at Stanford University Medical Center, Stanford,  California,  94305-5623,  United States; Recruiting
District of Columbia
      Children's National Medical Center, Washington,  District of Columbia,  20010-2970,  United States; Recruiting
Florida
      University of Florida Shands Cancer Center, Gainesville,  Florida,  32610-100277,  United States; Recruiting
Illinois
      Children's Memorial Hospital - Chicago, Chicago,  Illinois,  60614,  United States; Recruiting
Indiana
      Indiana University Cancer Center, Indianapolis,  Indiana,  46202-5289,  United States; Recruiting
Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231,  United States; Recruiting
Massachusetts
      Children's Hospital Boston, Boston,  Massachusetts,  02115,  United States; Recruiting
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States; Recruiting
Michigan
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0752,  United States; Recruiting
Minnesota
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States; Recruiting
Missouri
      Cardinal Glennon Children's Hospital, Saint Louis,  Missouri,  63104,  United States; Recruiting
      Children's Mercy Hospital, Kansas City,  Missouri,  64108,  United States; Recruiting
      Kansas City Cancer Centers - Central, Kansas City,  Missouri,  64111,  United States; Recruiting
      Siteman Cancer Center at Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  United States; Recruiting
      St. Louis Children's Hospital, Saint Louis,  Missouri,  63110,  United States; Recruiting
Nebraska
      UNMC Eppley Cancer Center at the University of Nebraska Medical Center, Omaha,  Nebraska,  68198-3330,  United States; Recruiting
New Jersey
      Cancer Center at Hackensack University Medical Center, Hackensack,  New Jersey,  07601,  United States; Recruiting
New York
      James P. Wilmot Cancer Center at University of Rochester Medical Center, Rochester,  New York,  14642,  United States; Recruiting
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting
      Mount Sinai Medical Center, New York,  New York,  10029,  United States; Recruiting
North Carolina
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1082,  United States; Recruiting
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States; Recruiting
Ohio
      Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University, Cleveland,  Ohio,  44106-5065,  United States; Recruiting
Oregon
      Cancer Institute at Oregon Health and Science University, Portland,  Oregon,  97239-3098,  United States; Recruiting
Pennsylvania
      Abramson Cancer Center at the University of Pennsylvania, Philadelphia,  Pennsylvania,  19104-4283,  United States; Recruiting
Tennessee
      Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center, Nashville,  Tennessee,  37232-6310,  United States; Recruiting
Texas
      MD Anderson Cancer Center at University of Texas, Houston,  Texas,  77030-4009,  United States; Recruiting
      Texas Transplant Institute, San Antonio,  Texas,  78229,  United States; Recruiting
Utah
      Huntsman Cancer Institute at University of Utah, Salt Lake City,  Utah,  84112,  United States; Recruiting
Washington
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109-1024,  United States; Recruiting

Study chairs or principal investigators

John Reid Wingard, MD,  Study Chair,  University of Florida Shands Cancer Center   

Study ID Numbers:  CDR0000349374; BMTCTN-0101; UF-G-074-2003; FHCRC-1808.00; NCT00075803
Record last reviewed:  September 2004
Last Updated:  April 4, 2005
Record first received:  January 9, 2004
ClinicalTrials.gov Identifier:  NCT00075803
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08