Overview

Busulfan and Fludarabine in Patients With AML and MDS

Status:
Completed

Trial end date:
2008-11-01

Target enrollment:
0

Participant gender:
All

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.

Phase:

Phase 2

Accepts Healthy Volunteers?

Details

Lead Sponsor:

M.D. Anderson Cancer Center

Treatments:

Busulfan
Fludarabine
Fludarabine phosphate
Vidarabine

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.