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

Sponsor:	M.D. Anderson Cancer Center
Information provided by (Responsible Party):	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00469144

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 III

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:

MedlinePlus related topics: Acute Myeloid Leukemia Cancer Leukemia Myelodysplastic Syndromes

Drug Information available for: Busulfan Fludarabine Fludarabine monophosphate

U.S. FDA Resources

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 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Fixed-Dose Busulfan + Fludarabine	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	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:

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

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:

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

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:	December 15, 2011
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 monophosphate
Fludarabine

Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on February 09, 2012