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

NCT00469144 | Completed Phase 3 Results DMC

• 3 other identifiers: 2005-0366NCI-2012-01475CA55164
• Study Type: interventional
• Target: 233
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Myelodysplastic Syndrome; Leukemia; Acute Myeloid Leukemia

Keywords

Stem Cell Transplantation; Leukemia; Busulfan; Fludarabine; MDS; AML

Outcome Measures

Primary Outcomes (2)

• Treatment-related Mortality (TRM)

  Time to failure (TTF) defined as either disease recurrence or death, from the time of bone marrow transplant (BMT) and reported as TRM at 100 days and 1 year. Treatment period defined as BMT Day -9 for patients treated on the PK-guided treatment arm, and day -7 for patients receiving the fixed-dose busulfan treatment through BMT Day +28. The post study surveillance period is defined as BMT Day +29 through BMT Day +100. Bone marrow aspirate with cytogenetics at approximately one (1) month and three (3) months, or as clinically indicated. Response Criteria is measured by the bone marrow aspirate to determine it has leukemic blast. Bone marrow blast less than 5% is considered to be a complete response.

  From transplant at Day 0 to Day 100 and 1 year following transplant

• 3 Year Progression Free Survival

  PFS defined as length of time either due to disease recurrence or death, from the time of stem cell infusion (Bone marrow or PBPC) to 3 years. Response Criteria is measured by the bone marrow aspirate to determine it has leukemic blast. Bone marrow blast less than 5% is considered to be a complete response.

  3 years

Study Arms (2)

Fixed-Dose Busulfan + Fludarabine

EXPERIMENTAL

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; Drug: Fludarabine

Adjusted Dose Busulfan + Fludarabine

EXPERIMENTAL

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; Drug: Fludarabine

Interventions

Busulfan DRUG

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 area under curve (AUC) of 6,000 microMol-min ± 10%.

Adjusted Dose Busulfan + Fludarabine; Fixed-Dose Busulfan + Fludarabine

Fludarabine DRUG

40 mg/m\^2 IV Daily Over 1 Hour x 4 Days

Adjusted Dose Busulfan + Fludarabine; Fixed-Dose Busulfan + Fludarabine

Eligibility Criteria

• Age: Up to 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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. Forced expiratory volume at one second (FEV1), forced vital capacity (FVC) and diffusion capacity of lung for carbon monoxide (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%.
• Serum glutamate pyruvate transaminase (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-human chorionic gonadotropin (HCG) pregnancy test in all women of child-bearing-potential in accordance with departmental routine).

You may not qualify if:

• \) None.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid, Acute

Interventions

Busulfan; fludarabine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Histologic Type; Neoplasms; Leukemia, Myeloid

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Richard E. Champlin, MD/Chair, Stem Cell Transplantation
• Organization: University of Texas (UT) MD Anderson Cancer Center

rchampli@mdanderson.org

713-792-3618

Study Officials

• Richard E. Champlin, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2007
• First Posted: May 4, 2007
• Study Start: June 1, 2005
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: January 19, 2021
• Results First Posted: January 19, 2021

Record last verified: 2021-01

Locations

US (1)