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

Sponsored by:	M.D. Anderson Cancer Center
Information provided by:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00469144

Purpose

Primary Objectives:

To determine if busulfan (Bu) given in pharmacokinetically adjusted dose to yield a blood daily AUC of 6,000 microMol-min is superior to a fixed dose of 130 mg/m2 to prevent treatment failure (relapse or death from any cause) in patients with acute myelogenous leukemia and myelodysplastic syndrome.

This dose will be given intravenously over three hours once daily for four (4) days, each dose preceded by Fludarabine at a dose of 40 mg/m2, as preparation for bone marrow or peripheral blood progenitor cell transplantation.
To determine the outcomes of AML/MDS patients undergoing treatment with this regimen. Data regarding engraftment, toxicity, relapse rate, long-term overall and disease-free survival will be collected.
To describe the plasma pharmacokinetics of busulfan when administered intravenously in this regimen.
To determine if the uniformly delivered variant of the Busulfan-Fludarabine regimen (daily AUC approximately 6,000 microMol-min ±10%) will confer a survival advantage compared with the fixed-dose delivery regimen (daily AUC approximately 5,000 microMol-min, range 3,500-7,500).

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

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood

Drug Information available for: Busulfan Fludarabine Fludarabine monophosphate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Uncontrolled, Parallel Assignment, Safety/Efficacy Study
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)

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

Primary Outcome Measures:

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. [ Time Frame: 4 Years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The safety of dosing based on blood levels will also be studied. [ Time Frame: 4 Years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	230
Study Start Date:	June 2005
Estimated Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Fixed-Dose Busulfan + Fludarabine	Drug: Busulfan Arm 1 = 130 mg/m^2 IV Daily Over Three Hours x 4 Days; Arm 2 = 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
2: Experimental Adjusted Dose Busulfan + Fludarabine	Drug: Busulfan Arm 1 = 130 mg/m^2 IV Daily Over Three Hours x 4 Days; Arm 2 = 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

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Eligibility

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

Criteria

Inclusion Criteria:

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.
Myelodysplastic syndromes with intermediate or high risk International Prognostic Scoring System score.
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).
No active infection. Protocol PI will be final arbiter if there is uncertainty regarding whether a previous infection is resolved.
age <=65.
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.
ZUBROD performance status < 2.
Life expectancy is not severely limited by concomitant illness and expected to be > 12 weeks.
Left ventricular ejection fraction > 45% No uncontrolled arrhythmias or symptomatic cardiac disease.
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
Serum creatinine </= 1.5 mg%.
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.
No effusion or ascites >1L prior to drainage.
HIV-negative.
Female patient is not pregnant (negative B-HCG pregnancy test in all women of child-bearing-potential in accordance with departmental routine).
Patient or patient's legal representative, parent(s) or guardian able to sign informed consent.
No prior autologous stem cell transplants

Exclusion Criteria: None

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00469144

Contacts

Contact: Richard E. Champlin, MD

713-792-8750

Locations

United States, Texas
U.T.M.D. Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Richard E. Champlin, MD

Sponsors and Collaborators

M.D. Anderson Cancer Center

Investigators

Principal Investigator:

Richard E. Champlin, MD

U.T.M.D. Anderson Cancer Center

More Information

Additional Information:

UT MD Anderson Cancer Center This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	U.T.M.D. Anderson Cancer Center ( Richard E. Champlin, MD/Chair )
Study ID Numbers:	2005-0366
Study First Received:	May 3, 2007
Last Updated:	January 5, 2009
ClinicalTrials.gov Identifier:	NCT00469144 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:

Stem Cell Transplantation
Leukemia
Busulfan

Fludarabine
MDS
AML

Study placed in the following topic categories:

Antimetabolites
Immunologic Factors
Precancerous Conditions
Hematologic Diseases
Myelodysplastic Syndromes
Leukemia, Myeloid
Fludarabine monophosphate
Leukemia, Myeloid, Acute
Immunosuppressive Agents

Leukemia
Preleukemia
Acute Myelocytic Leukemia
Acute Myeloid Leukemia, Adult
Busulfan
Antineoplastic Agents, Alkylating
Fludarabine
Bone Marrow Diseases
Alkylating Agents

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Precancerous Conditions
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Leukemia, Myeloid, Acute
Leukemia
Preleukemia
Pathologic Processes
Syndrome
Therapeutic Uses
Alkylating Agents

Disease
Neoplasms by Histologic Type
Hematologic Diseases
Myelodysplastic Syndromes
Leukemia, Myeloid
Fludarabine monophosphate
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Busulfan
Myeloablative Agonists
Fludarabine
Antineoplastic Agents, Alkylating
Bone Marrow Diseases

ClinicalTrials.gov processed this record on May 06, 2009