Posaconazole Versus Micafungin for Prophylaxis Against Invasive Fungal Infections During Neutropenia in Patients Undergoing Chemotherapy for Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia or Myelodysplastic Syndrome
Condition: Acute Myelogenous Leukemia; Myelodysplastic Syndrome
MeSH terms: Mycoses; Invasive Fungal Infections; Leukemia; Preleukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Neutropenia; Syndrome
Intervention: micafungin; posaconazole
Intervention description: Micafungin 100 mg intravenously once daily. Randomized treatment will be initiated 24-48 h after completion of the last dose of chemotherapy.; Posaconazole 400 mg orally twice daily. Randomized treatment will be initiated 24-48 h after completion of the last dose of chemotherapy.
Intervention MeSH terms: Posaconazole; Micafungin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 113.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: MICAFUNGIN; POSACONAZOLE; antifungal; prolonged neutropenia; 10-038

Summary:

      The purpose of this study is to compare the effects, good and/or bad, of posaconazole and
      micafungin in preventing fungal infections after chemotherapy for acute leukemia or
      myelodysplastic syndrome. When people take chemotherapy, they are more likely to get
      infections. Posaconazole has been approved for the prevention of fungal infections in
      patients who receive induction chemotherapy for acute leukemia and myelodysplastic syndrome.
      Posaconazole is available only as an oral suspension and has to be given with food. After
      chemotherapy, many patients are not able to tolerate food or oral medication because of
      severe mucositis. Patients unable to tolerate food and oral medications cannot take
      posaconazole.

      Micafungin is an antifungal medication that is given only intravenously. Micafungin is
      approved for the treatment of certain fungal infections and for preventing fungal infections
      in patients who receive bone marrow transplant. The investigators know that micafungin is
      safe. Micafungin has not been tested for the prevention of fungal infections in patients
      receiving chemotherapy for acute leukemia and myelodysplastic syndrome. Because micafungin is
      given by vein, it can be given even in patients who cannot take food or medications by mouth
      after chemotherapy. In this study the investigators want to compare micafungin to
      posaconazole when given for the prevention of fungal infections in leukemia and
      myelodysplastic syndrome patients.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects of greater than or equal to 18 years of age of either sex and of any race.

        Disease definition:

          -  Anticipated or documented prolonged neutropenia (ANC<500/mm3 [0.5x109/L]) at baseline
             or likely to develop within 3 to 5 days and lasting for at least 7 days due to:

          -  Intensive induction chemotherapy for new diagnosis of acute myelogenous leukemia,
             acute lymphocytic leukemia or myelodysplastic syndrome receiving standard
             anthracycline based chemotherapy

          -  Re-induction of acute myelogenous or lymphocytic leukemia after primary relapse

          -  Myelodysplastic syndromes requiring induction (myelosuppressive) chemotherapy

          -  Female subjects of childbearing potential must have a negative serum pregnancy test as
             per MSKCC guidelines.

          -  Able to swallow oral medications

        Exclusion Criteria:

          -  Subjects with history of presumed or proven invasive fungal infection within 30 days
             of randomization.

          -  Subjects who are taking the following:

        Drugs known to interact with posaconazole and that may lead to life-threatening side
        effects (terfenadine, cisapride, and ebastine at entry or within 24 hours before entry, or
        astemizole at entry or within 10 days before entry); b. Drugs known to lower the serum
        concentration/efficacy of posaconazole: cimetidine, rifampin, carbamazepine, phenytoin,
        rifabutin, barbiturates, and isoniazid at entry or within 24 hours before entry; c.
        Subjects who are planned to receive > 2mg flat dose of vinca alkaloids.

          -  Subjects with a history of hypersensitivity or idiosyncratic reactions to azole
             agents.

          -  Subjects with renal insufficiency (estimated creatinine clearance less than 20
             mL/minute at baseline or likely to require dialysis during the study).

          -  Subjects having an electrocardiogram with a prolonged QTc interval by manual reading:
             QTc greater than 490 msec.

          -  Subjects with moderate or severe liver dysfunction at baseline, defined as aspartate
             aminotransferase, alanine aminotransferase, or alkaline phosphatase levels greater
             than 5 times the upper limit of normal (ULN), or a total bilirubin level greater than
             3 times the ULN.

          -  Subjects who are undergoing re-induction chemotherapy and have participated in this
             study during their first induction chemotherapy.

          -  Subjects who will be receiving dasatinib.