IV Busulfan With Allo-BMT: Study for Patients With Acute Myelogenous Leukemia and Myelodysplastic Syndrome
Condition: Myelodysplastic Syndrome; Leukemia; Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid, Acute; Preleukemia; Leukemia, Myeloid; Myelodysplastic Syndromes; Syndrome
Intervention: Busulfan; Fludarabine
Intervention description: Fixed Dose = 130 mg/m^2 IV Daily Over Three Hours x 4 Days.
Adjusted Dose = 32 mg/m^2 IV Over 2 Hours Test Dose x 1 Day.
Proceeding dosage level determined by pharmacokinetic studies to achieve a daily area under curve (AUC) of 6,000 microMol-min ± 10%.; 40 mg/m^2 IV Daily Over 1 Hour x 4 Days
Intervention MeSH terms: Fludarabine; Busulfan
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 233.0
Sex: All
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Stem Cell Transplantation; Leukemia; Busulfan; Fludarabine; MDS; AML

Summary:

      The goal of this clinical research study is to learn if giving busulfan in a dose based on
      blood levels, along with a fixed (unchanging) dose of fludarabine, is more effective and
      causes fewer side effects for AML or myelodysplastic syndrome patients than the standard
      method of giving a fixed busulfan dose based on body size, along with a fixed dose of
      fludarabine. The safety of dosing based on blood levels will also be studied.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Acute myeloid leukemia past first remission, in first or subsequent relapse, in first
             remission (cytogenetics other than t(8;21, inv 16, t(15;17)) or induction failures.
             Only myeloid leukemia but not biphenotypic leukemia is allowed on this study.

          2. Myelodysplastic syndromes with intermediate or high risk International Prognostic
             Scoring System score

          3. Patient has not been administered any other systemic chemotherapeutic drug (including
             Mylotarg) within 21 days prior to trial enrollment (BMT Day -7 or day -9 for the
             test-dose arm of the study). Hydroxyurea is permitted if indicated to control
             induction refractory disease, and IT chemotherapy is allowed if indicated as
             maintenance treatment for previously diagnosed leptomeningeal disease, that has been
             in remission for at least 3 months prior to enrollment on this study).

          4. No active infection. Protocol PI will be final arbiter if there is uncertainty
             regarding whether a previous infection is resolved.

          5. age <=65

          6. Patients must have a matched related or unrelated donor willing to donate. A donor who
             is HLA identical or mismatched in 1 locus on Class I [HLA, A or B], or molecularly
             mismatched in 1 locus on Class II [HLA, DR or DQ] is also acceptable.

          7. ZUBROD performance status <2

          8. Life expectancy is not severely limited by concomitant illness and expected to be >12
             weeks.

          9. Left ventricular ejection fraction >45% No uncontrolled arrhythmias or symptomatic
             cardiac disease.

         10. No symptomatic pulmonary disease. Forced expiratory volume at one second (FEV1),
             forced vital capacity (FVC) and diffusion capacity of lung for carbon monoxide (DLCO)
             >/= 50% of expected corrected for hemoglobin. In patients </= 7 years pulmonary
             function will be assessed per pediatric BMT routine

         11. Serum creatinine </= 1.5 mg%.

         12. Serum glutamate pyruvate transaminase (SGPT) </= 200 IU/ml, serum bilirubin and
             alkaline phosphatase within accepted laboratory standard normal limits or considered
             not clinically significant. No evidence of chronic active hepatitis or cirrhosis. If
             positive hepatitis serology, discuss with Study Chairman and consider liver biopsy.

         13. No effusion or ascites >1L prior to drainage.

         14. HIV-negative.

         15. Female patient is not pregnant (negative B-human chorionic gonadotropin (HCG)
             pregnancy test in all women of child-bearing-potential in accordance with departmental
             routine).

         16. Patient or patient's legal representative, parent(s) or guardian able to sign informed
             consent.

         17. No prior autologous stem cell transplants

        Exclusion Criteria:

        1) None.