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

• Status: Completed
• Trial end date: 2007-09-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Medical College of Wisconsin
• Collaborators: Blood and Marrow Transplant Clinical Trials Network; National Cancer Institute (NCI); National Heart, Lung, and Blood Institute (NHLBI); National Marrow Donor Program
• Treatments: Fluconazole; Voriconazole

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