Busulfan and Fludarabine in Patients With AML and MDS

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00502905
First received: July 16, 2007
Last updated: May 23, 2012
Last verified: May 2012
  Purpose

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.

Condition Intervention Phase
Leukemia
Drug: Busulfan
Drug: Fludarabine
Phase 2

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

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Number of Participants With Successful Engraftment [ Time Frame: Study period one week prior to transplant through post Day 28 ] [ Designated as safety issue: No ]
    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.


Enrollment: 200
Study Start Date: October 2003
Study Completion Date: November 2008
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Busulfan
130 mg/m^2 injected through the intravenous catheter over three hours, once a day, for four days, starting immediately after Fludarabine.
Other Names:
  • Busulfex
  • Myleran
Drug: Fludarabine
40 mg/m^2 through a central venous catheter over one hour, once a day, for four days.
Other Names:
  • Fludarabine Phosphate
  • Fludara

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.

  Eligibility

Ages Eligible for Study:   up to 66 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00502905

Locations
United States, Texas
U.T.M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Richard E. Champlin, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00502905     History of Changes
Other Study ID Numbers: ID01-011
Study First Received: July 16, 2007
Results First Received: April 17, 2012
Last Updated: May 23, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Acute Myeloid Leukemia
Myelodysplastic Syndromes
Busulfan
Busulfex
Myleran
Fludarabine
Fludarabine Phosphate
Fludara

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Leukemia, Myeloid
Neoplasms
Neoplasms by Histologic Type
Precancerous Conditions
Busulfan
Fludarabine
Fludarabine phosphate
Vidarabine
Alkylating Agents
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antiviral Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014