Oral Posaconazole Three Times Per Day vs Weekly High Dose Amphotericin B Lipid Complex (ABLC)
Condition: Invasive Fungal Infections; Hematologic Malignancies
MeSH terms: Infections; Mycoses; Invasive Fungal Infections; Neoplasms; Hematologic Neoplasms
Intervention: Posaconazole; ABLC
Intervention description: 200 mg three times daily by mouth up to 6 weeks (Days 1-42); 7.5 mg/kg of ABLC intravenously infused over 4-6 hours once per week, for up to 6 weeks (from Day 1 through Day 42)
Intervention MeSH terms: Amphotericin B; Posaconazole
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hematologic Malignancies; Blood Cancer; Lymphatic Cancer; Amphotericin B Lipid Complex; Amphotericin B; ABLC; Fungizone; Noxafil; SCH56592; Posaconazole; Invasive fungal infections; IFI; Hematopoietic Stem Cell Transplant; HSCT; Bone Marrow Transplant; Allogeneic hematopoietic stem cell transplant

Summary:

      The objective of this study is to compare the safety and efficacy of ABLC versus oral
      Posaconazole in the prevention of invasive fungal infections in high risk patients with
      hematologic malignancies or hematopoietic stem cell transplant.

      Primary objective is to demonstrate the low toxicity rate and low rate of invasive fungal
      infections associated with ABLC or Posaconazole prophylaxis.

      Secondary objective will be to compare the cost effectiveness of these two prophylactic
      regimens.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subjects: 18 years of age or above.

          2. Any allogeneic hematopoietic stem cell transplant (HSCT) patient who is at risk of
             invasive fungal infection (IFI) within 6 months of the transplant will be eligible for
             the study according to HSCT institutional anti-fungal prophylaxis guidelines.

          3. Subjects must be willing to give written informed consent and able to adhere to dosing
             and study visit schedule.

          4. Female subjects of childbearing potential must have a negative serum pregnancy test
             (beta-human chorionic gonadotropin [hCG]) at Baseline or within 96 hours before the
             start of study drug.

          5. Female subjects of childbearing potential must agree to use a medically accepted
             method of contraception prior to screening, while receiving protocol-specified
             medication, and for 30 days after stopping the medication. Acceptable methods of
             contraception include condoms with/without a spermicidal agent, diaphragm or cervical
             cap with spermicide, medically prescribed IUD (intrauterine device), oral/injectable
             hormonal contraceptive, surgical sterilization (e.g. hysterectomy/tubal ligation).

        Exclusion Criteria:

          1. Subjects previously treated with antifungal therapy (voriconazole, fluconazole, or
             itraconazole) for proven or probable IFI within 30 days of enrollment.

          2. Subjects who have taken the following drugs: terfenadine, cisapride, primazide, and
             ebastine; that are known to interact with azoles and that may lead to life-threatening
             side effects, within 24 hours before study drug administration. And astemizole within
             7 days before study drug administration.

          3. Subjects who have taken the following drugs: cimetidine, rifampin, carbamezapine,
             phenytoin, rifabutin, barbiturates, isoniazid, and vinca alkaloids (vincristine,
             vinblastine); that are known to lower the serum concentration/efficacy of azole
             antifungal agents, within 24 hours before study drug administration.

          4. Subjects with a history of hypersensitivity or idiosyncratic reactions to azole agents
             or Amphotericin B.

          5. Subjects on other nephrotoxic agents (e.g. foscarnet).

          6. Patients who are unable to take pills.

          7. Subjects with proven or probable invasive fungal infection.

          8. Subjects with renal insufficiency (estimated creatine clearance less than 50mL/minute
             at Baseline or likely to require dialysis during the study).

          9. Subjects having ECG with a prolonged QTc interval by manual reading: QTc greater than
             500 msec. at Baseline.

         10. Subjects with moderate or severe liver dysfunction at baseline, defined as aspartate
             amniotransferase (AST), alanine amniotransferase (ALT) and / or a total bilirubin
             level greater than 3 times the upper limit of normal (ULN).

         11. Women who are breast feeding, pregnant, or intend to become pregnant during the course
             of the study.

         12. Prior enrollment in this study.