Pharmacokinetics of Anidulafungin (Ecalta ®) Intravenous Given to Patients at High Risk for Developing Invasive Fungal Disease
Condition: Leukemia; Myelodysplastic Syndrome; Leukemia, Myeloid, Acute
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to study the pharmacokinetics of anidulafungin (Ecalta ®) given
      intravenously as antifungal prophylaxis to recipients of an allogeneic haematopoietic stem
      cell transplant following myeloablative chemotherapy or patients receiving intensive
      chemotherapy for AML-MDS who are at high risk for developing invasive fungal disease.
    

Detailed description: 
      Alternate dosing strategies of echinocandin drugs might provide a better efficacy in the
      treatment of fungal infections as compared to the current label dosing strategy. Before
      conducting a controlled efficacy trial of echinocandins in haematology patients, the
      pharmacokinetics of these alternate dosing strategies need to be tested before bringing this
      idea to practice in a large randomised trial.

      Therefore we want to conduct a pharmacokinetic study with anidulafungin given every 48 hours
      or every 72 hours. This research can be performed best in a group of patients at high risk
      for developing invasive fungal infections.

      Recipients of an allogeneic haematopoietic stem cell transplant (HSCT) or patients receiving
      intensive chemotherapy for acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS)
      are at a relatively high risk of developing invasive fungal infections and are therefore
      candidates for primary prophylaxis. However, the options are limited to fluconazole which
      affords no protection against mould infections. Amphotericin B is not considered useful
      because of its desoxycholate formulation has too many side effects and its lipid formulations
      are too expensive nor have the broad-spectrum triazoles itraconazole and voriconazole proved
      their value in this setting. Anidulafungin is the first of a new class of antifungal drugs
      quite unlike any others attacking specifically the ß 1-3 -D-glucan synthase of the cell wall.
      It has relatively few side effects and appears safe and effective for treating Aspergillus
      and Candida infections. Since these two genera account for 90% of fungal infections in HSCT
      recipients the drug would seem an ideal candidate for prophylaxis.

      Importantly, nothing is known about the pharmacokinetics of alternate dosing regimens of
      anidulafungin in this patient population. Therefore a pharmacokinetic study of a homogenous
      cohort of patients is necessary to test the assumption, that adequate exposure is obtained
      with alternate dosing and that it is safe.
    

Intervention name(s): anidulafungin 200 mg q48h; anidulafungin 300 mg q72h
Intervention type(s): Drug; Drug
Intervention description(s): Day 1-15: anidulafungin 200 mg q48h IV maintenance dose (8 dosages); Day 1-13: anidulafungin 300 mg q72h IV maintenance dose (5 dosages)
Other intervention name(s): Ecalta; Ecalta
Intervention MeSH terms: Anidulafungin
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: anidulafungin; antifungal prophylaxis; allogeneic haematopoietic stem cell transplant; myeloablative chemotherapy; AML-MDS; pharmacokinetics