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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)


Phase 3
16 Years
55 Years
Not Enrolling
Both
Leukemia, Myelodysplastic Syndromes

Thank you

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 CenterTucson, Arizona  85724
Fred Hutchinson Cancer Research CenterSeattle, Washington  98109
University of Michigan Comprehensive Cancer CenterAnn Arbor, Michigan  48109-0752
Jonsson Comprehensive Cancer Center, UCLALos Angeles, California  90095-1781
Chao Family Comprehensive Cancer CenterOrange, California  92868
Stanford University Medical CenterStanford, California  94305-5408
University of Colorado Cancer CenterDenver, Colorado  80262
Albert B. Chandler Medical Center, University of KentuckyLexington, Kentucky  40536-0084
Barbara Ann Karmanos Cancer InstituteDetroit, Michigan  48201
University of Mississippi Medical CenterJackson, Mississippi  39216-4505
University of Washington Medical CenterSeattle, Washington  98195-6043
CCOP - WichitaWichita, Kansas  67214-3882
University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811
Loyola University Medical CenterMaywood, Illinois  60153
Henry Ford HospitalDetroit, Michigan  48202
Huntsman Cancer InstituteSalt Lake City, Utah  84112
Tulane University School of MedicineNew Orleans, Louisiana  70112
St. Louis University Health Sciences CenterSaint Louis, Missouri  63110-0250
CCOP - Cancer Research for the OzarksSpringfield, Missouri  65807
CCOP - DaytonKettering, Ohio  45429
CCOP - Columbia River ProgramPortland, Oregon  97213
Wilford Hall - 59th Medical WingLackland Air Force Base, Texas  78236-5300
LDS HospitalSalt Lake City, Utah  84143
Swedish Cancer InstituteSeattle, Washington  98104
CCOP - Scott and White HospitalTemple, Texas  76508
Cancer Research Center of HawaiiHonolulu, Hawaii  96813
Cleveland Clinic Taussig Cancer CenterCleveland, Ohio  44195
University of Arkansas for Medical SciencesLittle Rock, Arkansas  72205
Cancer Center and Beckman Research Institute, City of HopeDuarte, California  91010-3000
USC/Norris Comprehensive Cancer Center and HospitalLos Angeles, California  90033-0804
University of Kansas Medical CenterKansas City, Kansas  66160-7353
MBCCOP - LSU Health Sciences CenterNew Orleans, Louisiana  70112
Louisiana State University Health Sciences Center - ShreveportShreveport, Louisiana  71130-3932
Boston Medical CenterBoston, Massachusetts  02118
Herbert Irving Comprehensive Cancer CenterNew York, New York  10032
Brooke Army Medical CenterFort Sam Houston, Texas  78234-6200
Texas Tech University Health Science CenterLubbock, Texas  79415
CCOP - Virginia Mason Research CenterSeattle, Washington  98101
CCOP - NorthwestTacoma, Washington  98405-0986
Scripps ClinicLa Jolla, California  92037
Sutter Cancer CenterSacramento, California  95816
Lucille Parker Markey Cancer Center, University of KentuckyLexington, Kentucky  40536-0093
Jewish Hospital of Cincinnati, Inc.Cincinnati, Ohio  45236
Oregon Cancer CenterPortland, Oregon  97201-3098
University of California Davis Cancer CenterSacramento, California  95817
University of Oklahoma Health Sciences CenterOklahoma City, Oklahoma  73104
St. Joseph Hospital - OrangeOrange, California  92868
Mountain States Tumor InstituteBoise, Idaho  83712
Methodist Health Care SystemSan Antonio, Texas  78229-3902
Scott and White ClinicTemple, Texas  76508
Louisiana State University School of MedicineNew Orleans, Louisiana  70112-2822
Alta Bates Comprehensive Cancer CenterBerkeley, California  94704
Providence St. Vincent Medical CenterPortland, Oregon  97225
Cancer Center of Kansas - WichitaWichita, Kansas  67214
Miami Valley HospitalDayton, Ohio  45409
St. Francis Medical CenterHonolulu, Hawaii  96817
Queen's Medical CenterHonolulu, Hawaii  96813
Good Samaritan Medical CenterPhoenix, Arizona  85062-2989
Northern California Cancer Specialists Medical ClinicWalnut Creek, California  94598
Memorial Medical CenterNew Orleans, Louisiana  70115
Cancer Research CenterBoston, Massachusetts  02118
St. John's Health SystemSpringfield, Missouri  65804
Legacy Cancer ServicesPortland, Oregon  97210
Health Science CenterLubbock, Texas  79430
Franciscan Health SystemTacoma, Washington  98401-2197