IV Busulfan With Allo-BMT: Study for Patients With Acute Myelogenous Leukemia and Myelodysplastic Syndrome

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00469144
First received: May 3, 2007
Last updated: September 3, 2013
Last verified: September 2013
  Purpose

The goal of this clinical research study is to learn if giving busulfan in a dose based on blood levels, along with a fixed (unchanging) dose of fludarabine, is more effective and causes fewer side effects for AML or myelodysplastic syndrome patients than the standard method of giving a fixed busulfan dose based on body size, along with a fixed dose of fludarabine. The safety of dosing based on blood levels will also be studied.


Condition Intervention Phase
Myelodysplastic Syndrome
Leukemia
Acute Myeloid Leukemia
Drug: Busulfan
Drug: Fludarabine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Study of Once Daily IV Busulfan With Fludarabine With Hemopoietic Stem Cell Transplantation for Acute Myelogenous Leukemia (AML) and Myelodysplastic Syndrome (MDS)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Time to failure (TTF) [ Time Frame: From transplant at Day 0 to Day 100 following transplant then quarterly thereafer (3, 6, 12 months) ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 230
Study Start Date: June 2005
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fixed-Dose Busulfan + Fludarabine
Busulfan Fixed Dose = 130 mg/m^2 IV Daily Over Three Hours x 4 Days. Fludarabine 40 mg/m^2 IV Daily Over 1 Hour x 4 Days.
Drug: Busulfan

Fixed Dose = 130 mg/m^2 IV Daily Over Three Hours x 4 Days.

Adjusted Dose = 32 mg/m^2 IV Over 2 Hours Test Dose x 1 Day.

Proceeding dosage level determined by pharmacokinetic studies to achieve a daily AUC of 6,000 microMol-min ± 10%.

Drug: Fludarabine
40 mg/m^2 IV Daily Over 1 Hour x 4 Days
Experimental: Adjusted Dose Busulfan + Fludarabine
Busulfan Adjusted Dose = 32 mg/m^2 IV Over 2 Hours Test Dose x 1 Day. Fludarabine 40 mg/m^2 IV Daily Over 1 Hour x 4 Days.
Drug: Busulfan

Fixed Dose = 130 mg/m^2 IV Daily Over Three Hours x 4 Days.

Adjusted Dose = 32 mg/m^2 IV Over 2 Hours Test Dose x 1 Day.

Proceeding dosage level determined by pharmacokinetic studies to achieve a daily AUC of 6,000 microMol-min ± 10%.

Drug: Fludarabine
40 mg/m^2 IV Daily Over 1 Hour x 4 Days

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Acute myeloid leukemia past first remission, in first or subsequent relapse, in first remission (cytogenetics other than t(8;21, inv 16, t(15;17)) or induction failures. Only myeloid leukemia but not biphenotypic leukemia is allowed on this study.
  2. Myelodysplastic syndromes with intermediate or high risk International Prognostic Scoring System score
  3. Patient has not been administered any other systemic chemotherapeutic drug (including Mylotarg) within 21 days prior to trial enrollment (BMT Day -7 or day -9 for the test-dose arm of the study). Hydroxyurea is permitted if indicated to control induction refractory disease, and IT chemotherapy is allowed if indicated as maintenance treatment for previously diagnosed leptomeningeal disease, that has been in remission for at least 3 months prior to enrollment on this study).
  4. No active infection. Protocol PI will be final arbiter if there is uncertainty regarding whether a previous infection is resolved.
  5. age <=65
  6. Patients must have a matched related or unrelated donor willing to donate. A donor who is HLA identical or mismatched in 1 locus on Class I [HLA, A or B], or molecularly mismatched in 1 locus on Class II [HLA, DR or DQ] is also acceptable.
  7. ZUBROD performance status <2
  8. Life expectancy is not severely limited by concomitant illness and expected to be >12 weeks.
  9. Left ventricular ejection fraction >45% No uncontrolled arrhythmias or symptomatic cardiac disease.
  10. No symptomatic pulmonary disease. FEV1, FVC and DLCO >/= 50% of expected corrected for hemoglobin. In patients </= 7 years pulmonary function will be assessed per pediatric BMT routine
  11. Serum creatinine </= 1.5 mg%.
  12. SGPT </= 200 IU/ml, serum bilirubin and alkaline phosphatase within accepted laboratory standard normal limits or considered not clinically significant. No evidence of chronic active hepatitis or cirrhosis. If positive hepatitis serology, discuss with Study Chairman and consider liver biopsy.
  13. No effusion or ascites >1L prior to drainage.
  14. HIV-negative.
  15. Female patient is not pregnant (negative B-HCG pregnancy test in all women of child-bearing-potential in accordance with departmental routine).
  16. Patient or patient's legal representative, parent(s) or guardian able to sign informed consent.
  17. No prior autologous stem cell transplants

Exclusion Criteria:

1) None.

  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: NCT00469144

Locations
United States, Texas
UT MD 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: NCT00469144     History of Changes
Other Study ID Numbers: 2005-0366
Study First Received: May 3, 2007
Last Updated: September 3, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Stem Cell Transplantation
Leukemia
Busulfan
Fludarabine
MDS
AML

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

ClinicalTrials.gov processed this record on August 19, 2014