Busulfan and Fludarabine in Patients With AML and MDS
Condition: Leukemia
MeSH terms: Leukemia
Intervention: Busulfan; Fludarabine
Intervention description: 130 mg/m^2 injected through the intravenous catheter over three hours, once a day, for four days, starting immediately after Fludarabine.; 40 mg/m^2 through a central venous catheter over one hour, once a day, for four days.
Intervention MeSH terms: Fludarabine; Fludarabine phosphate; Busulfan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 200.0
Sex: All
Maximum age: 66 Years
Healthy volunteers: No
Keywords: Acute Myeloid Leukemia; Myelodysplastic Syndromes; Busulfan; Busulfex; Myleran; Fludarabine; Fludarabine Phosphate; Fludara

Summary:

      Primary Objectives:

        1. To administer multiple doses of an intravenous formulation of busulfan (Bu) at a dose
           adjusted to yield a blood drug level with a median daily area under the plasma
           concentration curve (AUC) of approximately 6,500 µMol-min. This dose will be given
           intravenously over three hours once daily for four (4) days, in combination with
           Fludarabine at a dose of 40 mg/m2 as preparation for bone marrow or peripheral stern
           cell transplantation in patients with acute myeloid leukemia or myelodysplastic
           syndromes.

        2. To determine the outcome of Acute Myeloid Leukemia (AML)/myelodysplastic syndromes (MDS)
           patients undergoing treatment with this regimen. Data regarding engraftment, toxicity,
           relapse rate, long-term (disease-free) outcome, and overall survival will be collected.

        3. To determine the safety profile of this regimen when utilized as preparation for
           allogeneic transplantation.

        4. To describe the plasma pharmacokinetics of busulfan when administered intravenously in
           this regimen.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Acute leukemia past first remission, in first or subsequent relapse, in first
             remission (high-risk, i.e., cytogenetics other than t(8;21, inv 16, t(15;17)) or
             induction failures.

          2. Myelodysplastic syndromes in any clinical stage, excluding only patients who have
             isolated stable mono-cytopenia and who are clinically stable.

          3. Patient has not been administered any other systemic chemotherapeutic drug (including
             Mylotarg) within 21 days prior to trial enrollment (BMT Day -7 or BMT day -9).
             (Hydroxyurea and intrathecal chemotherapy is permitted).

          4. No uncontrolled infection.

          5. Patients up to age 65 will be eligible for this study.

          6. ALLOGENEIC TRANSPLANTATION:

             Patients should have an acceptable related or unrelated volunteer donor available for
             a bone marrow peripheral blood progenitor cell or cord blood transplant. Bone marrow
             and peripheral blood cell donors should be matched for at least 5 of 6 HLA A, B and DR
             loci. Cord blood donors should be matched for at least 4 of 6 A, B and DR loci.

          7. Life expectancy is not severely limited.

          8. Pulmonary, cardio, renal and liver function tests normal.

          9. In patients < 7 years pulmonary function will be assessed per pediatric BMT routine.

         10. No evidence of chronic active hepatitis or cirrhosis.

         11. HIV-negative.

         12. Female patient is not pregnant

         13. Signed informed consent.

         14. Patient admitted on Sunday, or Monday to allow for pharmacokinetic directed therapy.

        Exclusion Criteria:

        1) Not fulfilling eligibility criteria above.