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)
16 Years
55 Years
Both
Leukemia, Myelodysplastic Syndromes
Trial Information
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)
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Event-free survival
Outcome Time Frame:
every 6 months after stem cell infusion until death or 5 years
Safety Issue:
No
Principal Investigator
Jeanne E. Anderson, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Katmai Oncology Group
Authority:
United States: Federal Government
Study ID:
CDR0000067898
NCT ID:
NCT00005866
Start Date:
February 2000
Completion Date:
March 2006
Related Keywords:
- Leukemia
- Myelodysplastic Syndromes
- 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
- Leukemia
- Leukemia, Myeloid, Acute
- Leukemia, Myeloid
- Myelodysplastic Syndromes
- Preleukemia
Name | Location |
|---|---|
| Arizona Cancer Center | Tucson, Arizona 85724 |
| Fred Hutchinson Cancer Research Center | Seattle, Washington 98109 |
| University of Michigan Comprehensive Cancer Center | Ann Arbor, Michigan 48109-0752 |
| Jonsson Comprehensive Cancer Center, UCLA | Los Angeles, California 90095-1781 |
| Chao Family Comprehensive Cancer Center | Orange, California 92868 |
| Stanford University Medical Center | Stanford, California 94305-5408 |
| University of Colorado Cancer Center | Denver, Colorado 80262 |
| Albert B. Chandler Medical Center, University of Kentucky | Lexington, Kentucky 40536-0084 |
| Barbara Ann Karmanos Cancer Institute | Detroit, Michigan 48201 |
| University of Mississippi Medical Center | Jackson, Mississippi 39216-4505 |
| University of Washington Medical Center | Seattle, Washington 98195-6043 |
| CCOP - Wichita | Wichita, Kansas 67214-3882 |
| University of Texas Health Science Center at San Antonio | San Antonio, Texas 78284-7811 |
| Loyola University Medical Center | Maywood, Illinois 60153 |
| Henry Ford Hospital | Detroit, Michigan 48202 |
| Huntsman Cancer Institute | Salt Lake City, Utah 84112 |
| Tulane University School of Medicine | New Orleans, Louisiana 70112 |
| St. Louis University Health Sciences Center | Saint Louis, Missouri 63110-0250 |
| CCOP - Cancer Research for the Ozarks | Springfield, Missouri 65807 |
| CCOP - Dayton | Kettering, Ohio 45429 |
| CCOP - Columbia River Program | Portland, Oregon 97213 |
| Wilford Hall - 59th Medical Wing | Lackland Air Force Base, Texas 78236-5300 |
| LDS Hospital | Salt Lake City, Utah 84143 |
| Swedish Cancer Institute | Seattle, Washington 98104 |
| CCOP - Scott and White Hospital | Temple, Texas 76508 |
| Cancer Research Center of Hawaii | Honolulu, Hawaii 96813 |
| Cleveland Clinic Taussig Cancer Center | Cleveland, Ohio 44195 |
| University of Arkansas for Medical Sciences | Little Rock, Arkansas 72205 |
| Cancer Center and Beckman Research Institute, City of Hope | Duarte, California 91010-3000 |
| USC/Norris Comprehensive Cancer Center and Hospital | Los Angeles, California 90033-0804 |
| University of Kansas Medical Center | Kansas City, Kansas 66160-7353 |
| MBCCOP - LSU Health Sciences Center | New Orleans, Louisiana 70112 |
| Louisiana State University Health Sciences Center - Shreveport | Shreveport, Louisiana 71130-3932 |
| Boston Medical Center | Boston, Massachusetts 02118 |
| Herbert Irving Comprehensive Cancer Center | New York, New York 10032 |
| Brooke Army Medical Center | Fort Sam Houston, Texas 78234-6200 |
| Texas Tech University Health Science Center | Lubbock, Texas 79415 |
| CCOP - Virginia Mason Research Center | Seattle, Washington 98101 |
| CCOP - Northwest | Tacoma, Washington 98405-0986 |
| Scripps Clinic | La Jolla, California 92037 |
| Sutter Cancer Center | Sacramento, California 95816 |
| Lucille Parker Markey Cancer Center, University of Kentucky | Lexington, Kentucky 40536-0093 |
| Jewish Hospital of Cincinnati, Inc. | Cincinnati, Ohio 45236 |
| Oregon Cancer Center | Portland, Oregon 97201-3098 |
| University of California Davis Cancer Center | Sacramento, California 95817 |
| University of Oklahoma Health Sciences Center | Oklahoma City, Oklahoma 73104 |
| St. Joseph Hospital - Orange | Orange, California 92868 |
| Mountain States Tumor Institute | Boise, Idaho 83712 |
| Methodist Health Care System | San Antonio, Texas 78229-3902 |
| Scott and White Clinic | Temple, Texas 76508 |
| Louisiana State University School of Medicine | New Orleans, Louisiana 70112-2822 |
| Alta Bates Comprehensive Cancer Center | Berkeley, California 94704 |
| Providence St. Vincent Medical Center | Portland, Oregon 97225 |
| Cancer Center of Kansas - Wichita | Wichita, Kansas 67214 |
| Miami Valley Hospital | Dayton, Ohio 45409 |
| St. Francis Medical Center | Honolulu, Hawaii 96817 |
| Queen's Medical Center | Honolulu, Hawaii 96813 |
| Good Samaritan Medical Center | Phoenix, Arizona 85062-2989 |
| Northern California Cancer Specialists Medical Clinic | Walnut Creek, California 94598 |
| Memorial Medical Center | New Orleans, Louisiana 70115 |
| Cancer Research Center | Boston, Massachusetts 02118 |
| St. John's Health System | Springfield, Missouri 65804 |
| Legacy Cancer Services | Portland, Oregon 97210 |
| Health Science Center | Lubbock, Texas 79430 |
| Franciscan Health System | Tacoma, Washington 98401-2197 |
