Busulfan and Fludarabine in Patients With AML and MDS

Leukemia Clinical Trial

Official title:

A Phase II Study of High-Dose Intravenous Busulfan and Fludarabine With Allogeneic Marrow and Peripheral Blood Progenitor Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00502905
• Other study ID #: ID01-011
• Status: Completed
• Phase: Phase 2
• First received: July 16, 2007
• Last updated: May 23, 2012
• Start date: October 2003
• Est. completion date: November 2008

Study information

• Verified date: May 2012
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: November 2008
• Est. primary completion date: November 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 66 Years

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Drug:
• Busulfan
130 mg/m^2 injected through the intravenous catheter over three hours, once a day, for four days, starting immediately after Fludarabine.
• Fludarabine
40 mg/m^2 through a central venous catheter over one hour, once a day, for four days.

Locations

Country	Name	City	State
United States	U.T.M.D. Anderson Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Successful Engraftment	Successful Engraftment defined as first of 3 consecutive days with Absolute neutrophil count (ANC) equal to or more than 0.5 * 10^9/L. Failure to engraft by day +30 considered primary engraftment failure. Study period one week prior to transplant through post Day 28.	Study period one week prior to transplant through post Day 28	No

External Links

•   UT MD Anderson Cancer Center website