Comparison of Fluconazole vs Voriconazole to Treat Fungal Infections for Blood and Marrow Transplants (BMT CTN 0101)
Condition: Lymphoma; Infection; Leukemia
MeSH terms: Infections; Communicable Diseases; Mycoses
Intervention: Fluconazole; Voriconazole
Intervention description: 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.; 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.
Intervention MeSH terms: Fluconazole; Voriconazole
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 600.0
Sex: All
Minimum age: 2 Years
Healthy volunteers: No
Keywords: Myelodysplastic and Myeloproliferative Diseases

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. unrelated) and will be randomized to either the fluconazole or voriconazole arm
      in a 1:1 ratio.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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:

               1. Acute myelogenous leukemia (AML)

               2. Acute lymphocytic leukemia (ALL)

               3. Acute undifferentiated leukemia (AUL)

               4. Acute biphenotypic leukemia in first or second complete remission

               5. Chronic myelogenous leukemia (CML) in either chronic or accelerated phase

               6. One of the following myelodysplastic syndrome(s) (MDS):

                    1. Refractory anemia

                    2. Refractory anemia with ringed sideroblasts

                    3. Refractory cytopenia with multilineage dysplasia

                    4. Refractory cytopenia with multilineage dysplasia and ringed sideroblasts

                    5. Refractory anemia with excess blasts-1 (5-10% blasts)

                    6. Refractory anemia with excess blasts-2 (10-20% blasts)

                    7. MDS, unclassified

                    8. MDS associated with isolated del (5q)

                    9. Chronic myelomonocytic leukemia (CMML)

               7. 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)

        Exclusion Criteria:

          -  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)

          -  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