Back to resultsS9920 Busulfan Compared With Cyclophosphamide in Patients Undergoing Total-Body Irradiation Plus Peripheral Stem Cell Transplantation for Advanced Myelodysplastic Syndrome or Related Acute Myeloid Leukemia
Primary Purpose
Leukemia, Myelodysplastic Syndromes
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
busulfan
cyclophosphamide
cyclosporine
methotrexate
allogeneic bone marrow transplantation
radiation therapy
Sponsored by
About this trial
This is an interventional treatment trial for Leukemia focused on measuring 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
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
Sites / Locations
- Good Samaritan Medical Center
- Arizona Cancer Center
- University of Arkansas for Medical Sciences
- Alta Bates Comprehensive Cancer Center
- Cancer Center and Beckman Research Institute, City of Hope
- Scripps Clinic
- USC/Norris Comprehensive Cancer Center and Hospital
- Jonsson Comprehensive Cancer Center, UCLA
- St. Joseph Hospital - Orange
- Chao Family Comprehensive Cancer Center
- Sutter Cancer Center
- University of California Davis Cancer Center
- Stanford University Medical Center
- Northern California Cancer Specialists Medical Clinic
- University of Colorado Cancer Center
- Cancer Research Center of Hawaii
- Queen's Medical Center
- St. Francis Medical Center
- Mountain States Tumor Institute
- Loyola University Medical Center
- University of Kansas Medical Center
- CCOP - Wichita
- Cancer Center of Kansas - Wichita
- Albert B. Chandler Medical Center, University of Kentucky
- Lucille Parker Markey Cancer Center, University of Kentucky
- Louisiana State University School of Medicine
- MBCCOP - LSU Health Sciences Center
- Tulane University School of Medicine
- Memorial Medical Center
- Louisiana State University Health Sciences Center - Shreveport
- Boston Medical Center
- Cancer Research Center
- University of Michigan Comprehensive Cancer Center
- Barbara Ann Karmanos Cancer Institute
- Henry Ford Hospital
- University of Mississippi Medical Center
- St. Louis University Health Sciences Center
- St. John's Health System
- CCOP - Cancer Research for the Ozarks
- Herbert Irving Comprehensive Cancer Center
- Jewish Hospital of Cincinnati, Inc.
- Cleveland Clinic Taussig Cancer Center
- Miami Valley Hospital
- CCOP - Dayton
- University of Oklahoma Health Sciences Center
- Oregon Cancer Center
- Legacy Cancer Services
- CCOP - Columbia River Program
- Providence St. Vincent Medical Center
- Brooke Army Medical Center
- Wilford Hall - 59th Medical Wing
- Texas Tech University Health Science Center
- Health Science Center
- Methodist Health Care System
- University of Texas Health Science Center at San Antonio
- CCOP - Scott and White Hospital
- Scott and White Clinic
- Huntsman Cancer Institute
- LDS Hospital
- CCOP - Virginia Mason Research Center
- Swedish Cancer Institute
- Fred Hutchinson Cancer Research Center
- University of Washington Medical Center
- Franciscan Health System
- CCOP - Northwest
- Princess Margaret Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
treatment
Arm Description
Outcomes
Primary Outcome Measures
Event-free survival
Secondary Outcome Measures
Full Information
NCT ID
NCT00005866
First Posted
June 2, 2000
Last Updated
March 5, 2015
Sponsor
SWOG Cancer Research Network
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00005866
Brief Title
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
2. Study Status
Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
February 2000 (undefined)
Primary Completion Date
March 2004 (Actual)
Study Completion Date
March 2006 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
SWOG Cancer Research Network
Collaborators
National Cancer Institute (NCI)
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
240 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
treatment
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
busulfan
Intervention Description
arm 1: 0.44 mg/kg every 6 hours, IV over 2 hours, day -7 to -4
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Description
arm 2: 60 mg/kg every 24 hrs for 2 doses, IV over 2 hrs, days -5 and -4
Intervention Type
Drug
Intervention Name(s)
cyclosporine
Intervention Description
both arms per published schedule
Intervention Type
Drug
Intervention Name(s)
methotrexate
Intervention Description
GVHD: 15 mg/m2 day 1, 10 mg/m2 day 3, 6 and 11 by IV
Intervention Type
Procedure
Intervention Name(s)
allogeneic bone marrow transplantation
Intervention Description
day 0
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Intervention Description
both arms: 1200 cGy total dose (6 x 200 fractions)
Primary Outcome Measure Information:
Title
Event-free survival
Time Frame
every 6 months after stem cell infusion until death or 5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeanne E. Anderson, MD
Organizational Affiliation
Katmai Oncology Group
Official's Role
Study Chair
Facility Information:
Facility Name
Good Samaritan Medical Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85062-2989
Country
United States
Facility Name
Arizona Cancer Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
University of Arkansas for Medical Sciences
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
Alta Bates Comprehensive Cancer Center
City
Berkeley
State/Province
California
ZIP/Postal Code
94704
Country
United States
Facility Name
Cancer Center and Beckman Research Institute, City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010-3000
Country
United States
Facility Name
Scripps Clinic
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
USC/Norris Comprehensive Cancer Center and Hospital
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033-0804
Country
United States
Facility Name
Jonsson Comprehensive Cancer Center, UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-1781
Country
United States
Facility Name
St. Joseph Hospital - Orange
City
Orange
State/Province
California
ZIP/Postal Code
92613-5600
Country
United States
Facility Name
Chao Family Comprehensive Cancer Center
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Sutter Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95816
Country
United States
Facility Name
University of California Davis Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Stanford University Medical Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305-5408
Country
United States
Facility Name
Northern California Cancer Specialists Medical Clinic
City
Walnut Creek
State/Province
California
ZIP/Postal Code
94598
Country
United States
Facility Name
University of Colorado Cancer Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80010
Country
United States
Facility Name
Cancer Research Center of Hawaii
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96813
Country
United States
Facility Name
Queen's Medical Center
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96813
Country
United States
Facility Name
St. Francis Medical Center
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96817
Country
United States
Facility Name
Mountain States Tumor Institute
City
Boise
State/Province
Idaho
ZIP/Postal Code
83712
Country
United States
Facility Name
Loyola University Medical Center
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160-7357
Country
United States
Facility Name
CCOP - Wichita
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214-3882
Country
United States
Facility Name
Cancer Center of Kansas - Wichita
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
Facility Name
Albert B. Chandler Medical Center, University of Kentucky
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536-0084
Country
United States
Facility Name
Lucille Parker Markey Cancer Center, University of Kentucky
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536-0093
Country
United States
Facility Name
Louisiana State University School of Medicine
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112-2822
Country
United States
Facility Name
MBCCOP - LSU Health Sciences Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Tulane University School of Medicine
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Memorial Medical Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70115
Country
United States
Facility Name
Louisiana State University Health Sciences Center - Shreveport
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71130-3932
Country
United States
Facility Name
Boston Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Cancer Research Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
University of Michigan Comprehensive Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-0752
Country
United States
Facility Name
Barbara Ann Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201-1379
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
University of Mississippi Medical Center
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216-4505
Country
United States
Facility Name
St. Louis University Health Sciences Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110-0250
Country
United States
Facility Name
St. John's Health System
City
Springfield
State/Province
Missouri
ZIP/Postal Code
65804
Country
United States
Facility Name
CCOP - Cancer Research for the Ozarks
City
Springfield
State/Province
Missouri
ZIP/Postal Code
65807
Country
United States
Facility Name
Herbert Irving Comprehensive Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Jewish Hospital of Cincinnati, Inc.
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45236
Country
United States
Facility Name
Cleveland Clinic Taussig Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Miami Valley Hospital
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45409
Country
United States
Facility Name
CCOP - Dayton
City
Kettering
State/Province
Ohio
ZIP/Postal Code
45429
Country
United States
Facility Name
University of Oklahoma Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73190
Country
United States
Facility Name
Oregon Cancer Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97201-3098
Country
United States
Facility Name
Legacy Cancer Services
City
Portland
State/Province
Oregon
ZIP/Postal Code
97210
Country
United States
Facility Name
CCOP - Columbia River Program
City
Portland
State/Province
Oregon
ZIP/Postal Code
97213
Country
United States
Facility Name
Providence St. Vincent Medical Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97225
Country
United States
Facility Name
Brooke Army Medical Center
City
Fort Sam Houston
State/Province
Texas
ZIP/Postal Code
78234
Country
United States
Facility Name
Wilford Hall - 59th Medical Wing
City
Lackland Air Force Base
State/Province
Texas
ZIP/Postal Code
78236-5300
Country
United States
Facility Name
Texas Tech University Health Science Center
City
Lubbock
State/Province
Texas
ZIP/Postal Code
79423
Country
United States
Facility Name
Health Science Center
City
Lubbock
State/Province
Texas
ZIP/Postal Code
79430
Country
United States
Facility Name
Methodist Health Care System
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
University of Texas Health Science Center at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78284-7811
Country
United States
Facility Name
CCOP - Scott and White Hospital
City
Temple
State/Province
Texas
ZIP/Postal Code
76508
Country
United States
Facility Name
Scott and White Clinic
City
Temple
State/Province
Texas
ZIP/Postal Code
76508
Country
United States
Facility Name
Huntsman Cancer Institute
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
LDS Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84143
Country
United States
Facility Name
CCOP - Virginia Mason Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States
Facility Name
Swedish Cancer Institute
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109-1024
Country
United States
Facility Name
University of Washington Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195-6043
Country
United States
Facility Name
Franciscan Health System
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98401-2197
Country
United States
Facility Name
CCOP - Northwest
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405-0986
Country
United States
Facility Name
Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
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
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