Busulfan and Fludarabine in Patients With AML and MDS

NCT ID: NCT00502905

Last Updated: 2012-05-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-10-31
• Study Completion Date: 2008-11-30

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.

Conditions

Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Busulfan + Fludarabine

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.

Group Type: EXPERIMENTAL

Busulfan

Intervention Type: DRUG

130 mg/m\^2 injected through the intravenous catheter over three hours, once a day, for four days, starting immediately after Fludarabine.

Fludarabine

Intervention Type: DRUG

40 mg/m\^2 through a central venous catheter over one hour, once a day, for four days.

Interventions

Busulfan

130 mg/m\^2 injected through the intravenous catheter over three hours, once a day, for four days, starting immediately after Fludarabine.

Intervention Type: DRUG

Fludarabine

40 mg/m\^2 through a central venous catheter over one hour, once a day, for four days.

Intervention Type: DRUG

Other Intervention Names

Busulfex; Myleran; Fludarabine Phosphate; Fludara

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.

• Maximum Eligible Age: 66 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Richard E. Champlin, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

U.T.M.D. Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Related Links

http://www.mdanderson.org

UT MD Anderson Cancer Center website

Other Identifiers

ID01-011

Identifier Type: -

Identifier Source: org_study_id