Clinical trial NCT00005866: S9920 Busulfan Compared With Cyclophosphamide in Patients Undergoing Total-Body Irradiation Plus Peripheral Stem Cell Transplantation for Advanced Myelodysplastic Syndrome or Related Acute Myeloid Leukemia
Official title: A Phase III Randomized Study Comparing Busulfan-Total Body Irradiation Versus Cyclophosphamide-Total Body Irradiation Preparative Regimen in Patients With Advanced Myelodysplastic Syndrome (MDS) or MDS-Related Acute Myeloid Leukemia (AML) Undergoing HLA-Identical Sibling Peripheral Blood Stem Cell Transplantation, (A BMT Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Leukemia
Myelodysplastic Syndromes
Keywords: untreated adult acute myeloid leukemia
refractory anemia with excess blasts
refractory anemia with excess blasts in transformation
chronic myelomonocytic leukemia
secondary acute myeloid leukemia
de novo myelodysplastic syndromes
secondary myelodysplastic syndromes
childhood myelodysplastic syndromes
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-03-16
Enrollment: 240
Sex: ALL
Minimum age (years): 16
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill tumor cells. It is not yet known if total-body irradiation plus peripheral stem cell transplantation is more effective with busulfan or with cyclophosphamide for myelodysplastic syndrome or acute myeloid leukemia.

PURPOSE: Randomized phase III trial to compare the effectiveness of busulfan with that of cyclophosphamide in patients undergoing total-body irradiation plus peripheral stem cell transplantation for advanced myelodysplastic syndrome or related acute myeloid leukemia.

Detailed description: OBJECTIVES: I. Compare event free survival after total body irradiation (TBI) plus busulfan versus TBI plus cyclophosphamide followed by allogeneic peripheral blood stem cell transplantation in patients with advanced myelodysplastic syndrome (MDS) or MDS related acute myeloid leukemia. II. Determine the distribution of pharmacokinetic parameters for busulfan in those patients randomized to the busulfan treatment arm. III. Investigate the prognostic significance for event free survival of prior history of red cell transfusions, cytogenetic pattern, and of functional drug resistance at diagnosis in these patients. IV. Estimate the frequencies of cytogenetic and genetic changes during disease progression in these patients.

OUTLINE: This a randomized, multicenter study. Patients are stratified according to age (40 and under vs 41-55) and diagnosis and International Prognostic Scoring System (IPSS) risk group (myelodysplastic syndrome (MDS)/IPSS - intermediate 1 vs MDS/IPSS - intermediate 2 vs MDS/IPSS high risk vs MDS related acute myeloid leukemia). Patients are randomized to one of two treatment arms. Arm I: Patients receive busulfan IV over 2 hours every 6 hours on days -7 to -4 for a total of 16 doses. Arm II: Patients receive cyclophosphamide IV over 2 hours on days -5 and -4. Patients receive total body irradiation (TBI) twice a day on days -3 to -1; peripheral blood stem cell transplantation from genotypically HLA identical sibling on day 0; cyclosporine IV every 12 hours on days -1 to 60, and then tapering in the absence of graft versus host disease; and methotrexate IV on days 1, 3, 6, and 11. Patients are followed every 6 months for 5 years.

PROJECTED ACCRUAL: A total of 240 patients (120 per treatment arm) will be accrued for this study over 5 years.

Eligibility criteria: DISEASE CHARACTERISTICS: Cytologically confirmed myelodysplastic syndrome (MDS) Increased blasts (i.e., greater than 1 to 30% peripheral blood blasts and/or 5 to 30% bone marrow blasts) AND International Prognostic Score intermediate 1, intermediate 2, or high risk Refractory anemia with excess blasts OR Refractory anemia with excess blasts in transformation (no presence of auer rods as sole criteria) OR Chronic myelomonocytic leukemia Greater than 1% blasts in the peripheral blood and/or at least 5% blasts in the bone marrow OR MDS related acute myeloid leukemia Arising after documented MDS of at least 60 days Absolute peripheral blast count no greater than 5,000/mm3 Must have genotypically HLA identical sibling donor Must also be enrolled on SWOG-S9910 and SWOG-9007

PATIENT CHARACTERISTICS: Age: 16 to 55 Performance status: Zubrod 0-2 Life expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic: Not specified Renal: Not specified Other: No prior malignancy within past 5 years except: Adequately treated basal cell or squamous cell skin cancer Carcinoma in situ of the cervix Adequately treated stage I or II cancer in complete remission HIV negative Not pregnant or nursing Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: No autologous peripheral stem cell transplantation prior to diagnosis of myelodysplastic syndrome (MDS) or MDS related acute myeloid leukemia Chemotherapy: No prior chemotherapy for MDS or MDS related acute myeloid leukemia except oral chemotherapy to control leukocytosis or thrombocytosis (e.g., hydroxyurea or etoposide) Endocrine therapy: Not specified Radiotherapy: No radiotherapy prior to diagnosis of MDS or MDS related acute myeloid leukemia Surgery: Not specified

Primary outcomes:
measure: Event-free survival
timeFrame: every 6 months after stem cell infusion until death or 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Good Samaritan Medical Center
state: Arizona
city: Tucson
country: United States
facility: Arizona Cancer Center
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Berkeley
country: United States
facility: Alta Bates Comprehensive Cancer Center
state: California
city: Duarte
country: United States
facility: Cancer Center and Beckman Research Institute, City of Hope
state: California
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
city: Orange
country: United States
facility: St. Joseph Hospital - Orange
state: California
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center
state: California
city: Sacramento
country: United States
facility: Sutter Cancer Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Walnut Creek
country: United States
facility: Northern California Cancer Specialists Medical Clinic
state: California
city: Denver
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Honolulu
country: United States
facility: Cancer Research Center of Hawaii
state: Hawaii
city: Honolulu
country: United States
facility: Queen's Medical Center
state: Hawaii
city: Honolulu
country: United States
facility: St. Francis Medical Center
state: Hawaii
city: Boise
country: United States
facility: Mountain States Tumor Institute
state: Idaho
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas - Wichita
state: Kansas
city: Lexington
country: United States
facility: Albert B. Chandler Medical Center, University of Kentucky
state: Kentucky
city: Lexington
country: United States
facility: Lucille Parker Markey Cancer Center, University of Kentucky
state: Kentucky
city: New Orleans
country: United States
facility: Louisiana State University School of Medicine
state: Louisiana
city: New Orleans
country: United States
facility: MBCCOP - LSU Health Sciences Center
state: Louisiana
city: New Orleans
country: United States
facility: Tulane University School of Medicine
state: Louisiana
city: New Orleans
country: United States
facility: Memorial Medical Center
state: Louisiana
city: Shreveport
country: United States
facility: Louisiana State University Health Sciences Center - Shreveport
state: Louisiana
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Cancer Research Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Saint Louis
country: United States
facility: St. Louis University Health Sciences Center
state: Missouri
city: Springfield
country: United States
facility: St. John's Health System
state: Missouri
city: Springfield
country: United States
facility: CCOP - Cancer Research for the Ozarks
state: Missouri
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center
state: New York
city: Cincinnati
country: United States
facility: Jewish Hospital of Cincinnati, Inc.
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Dayton
country: United States
facility: Miami Valley Hospital
state: Ohio
city: Kettering
country: United States
facility: CCOP - Dayton
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Portland
country: United States
facility: Oregon Cancer Center
state: Oregon
city: Portland
country: United States
facility: Legacy Cancer Services
state: Oregon
city: Portland
country: United States
facility: CCOP - Columbia River Program
state: Oregon
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
city: Fort Sam Houston
country: United States
facility: Brooke Army Medical Center
state: Texas
city: Lackland Air Force Base
country: United States
facility: Wilford Hall - 59th Medical Wing
state: Texas
city: Lubbock
country: United States
facility: Texas Tech University Health Science Center
state: Texas
city: Lubbock
country: United States
facility: Health Science Center
state: Texas
city: San Antonio
country: United States
facility: Methodist Health Care System
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Temple
country: United States
facility: CCOP - Scott and White Hospital
state: Texas
city: Temple
country: United States
facility: Scott and White Clinic
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Salt Lake City
country: United States
facility: LDS Hospital
state: Utah
city: Seattle
country: United States
facility: CCOP - Virginia Mason Research Center
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Tacoma
country: United States
facility: Franciscan Health System
state: Washington
city: Tacoma
country: United States
facility: CCOP - Northwest
state: Washington
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: Katmai Oncology Group
name: Jeanne E. Anderson, MD
role: STUDY_CHAIR
References: