Clinical trial NCT00502905
Conditions: Leukemia
Keywords: Acute Myeloid Leukemia Myelodysplastic Syndromes Busulfan Busulfex Myleran Fludarabine Fludarabine Phosphate Fludara
Sponsor: M.D. Anderson Cancer Center
Start date: 2003-10-01; Completion date: 2008-11-01
Enrollment: 200 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief 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.

Detailed description:
Patients who agree to the optional pharmacology procedures #1 will initially receive a therapeutic test dose of busulfan to test the blood levels over time; this information will be used to determine the subsequent high-dose busulfan doses. Patients who do not agree to the optional pharmacology procedure will receive a fixed dose of busulfan as has previously been done for 3 years.

Patients in this study will then receive fludarabine through a central venous catheter over one hour, once a day, for four days. High-dose Busulfan will be injected through the catheter over three hours, once a day, for four days, starting immediately after fludarabine.

After two days of rest, the allogeneic bone marrow, peripheral blood stem cells or cord blood will then be given intravenously. Patients will receive the drug Granulocyte colony-stimulating factor (G-CSF - Neupogen) as an injection under the skin until their blood counts recover.

Patients will remain in the hospital for about 4-6 weeks. After discharge, patients will continue as outpatients in the hospital area until they are able to safely leave the immediate hospital area or for a minimum of 100 days after the transplant. Some patients may need to receive spinal taps with instillation of cytosine arabinoside and hydrocortisone several times over the year after transplantation. This is only for patients with a previous clinical history of leukemic involvement of the brain.

This is an investigational study. The FDA has approved the study drugs. Up to 200 patients will take part in this study. All will be enrolled at M. D. Anderson.

Arms: arm 1: Once a day for four days, Busulfan 130 mg/m\^2 through intravenous catheter over 3 hours immediately after Fludarabine 40 mg/m\^2 over 1 hour.
Interventions: intervention 1: Busulfan intervention 2: Fludarabine
Intervention descriptions: intervention 1: 130 mg/m\^2 injected through the intravenous catheter over three hours, once a day, for four days, starting immediately after Fludarabine. intervention 2: 40 mg/m\^2 through a central venous catheter over one hour, once a day, for four days.

Protocol documents: