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.

Condition	Treatment or Intervention	Phase
untreated adult acute myeloid leukemia secondary myelodysplastic syndrome de novo myelodysplastic syndrome refractory anemia with excess blasts in transformation refractory anemia with excess blasts Chronic Myelomonocytic Leukemia secondary acute myeloid leukemia	Drug: busulfan  Drug: cyclophosphamide  Drug: cyclosporine  Drug: methotrexate	Phase III

Further Study Details: 

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.

PROTOCOL 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.

Ages Eligible for Study:  16 Years   -   55 Years

Criteria

PROTOCOL ENTRY 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

--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

--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

Arizona
      Arizona Cancer Center, Tucson,  Arizona,  85724,  United States
      Good Samaritan Medical Center, Phoenix,  Arizona,  85062-2989,  United States
Arkansas
      University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States
California
      Alta Bates Comprehensive Cancer Center, Berkeley,  California,  94704,  United States
      Cancer Center and Beckman Research Institute, City of Hope, Duarte,  California,  91010-3000,  United States
      Chao Family Comprehensive Cancer Center, Orange,  California,  92868,  United States
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States
      Northern California Cancer Specialists Medical Clinic, Walnut Creek,  California,  94598,  United States
      Scripps Clinic, La Jolla,  California,  92037,  United States
      St. Joseph Hospital - Orange, Orange,  California,  92613-5600,  United States
      Stanford University Medical Center, Stanford,  California,  94305-5408,  United States
      Sutter Cancer Center, Sacramento,  California,  95816,  United States
      University of California Davis Cancer Center, Sacramento,  California,  95817,  United States
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90033-0804,  United States
Colorado
      University of Colorado Cancer Center, Denver,  Colorado,  80010,  United States
Hawaii
      Cancer Research Center of Hawaii, Honolulu,  Hawaii,  96813,  United States
      Queen's Medical Center, Honolulu,  Hawaii,  96813,  United States
      St. Francis Medical Center, Honolulu,  Hawaii,  96817,  United States
Idaho
      Mountain States Tumor Institute, Boise,  Idaho,  83712,  United States
Illinois
      Loyola University Medical Center, Maywood,  Illinois,  60153,  United States
Kansas
      Cancer Center of Kansas - Wichita, Wichita,  Kansas,  67214,  United States
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States
      University of Kansas Medical Center, Kansas City,  Kansas,  66160-7357,  United States
Kentucky
      Albert B. Chandler Medical Center, University of Kentucky, Lexington,  Kentucky,  40536-0084,  United States
      Lucille Parker Markey Cancer Center, University of Kentucky, Lexington,  Kentucky,  40536-0093,  United States
Louisiana
      Louisiana State University Health Sciences Center - Shreveport, Shreveport,  Louisiana,  71130-3932,  United States
      Louisiana State University School of Medicine, New Orleans,  Louisiana,  70112-2822,  United States
      MBCCOP - LSU Health Sciences Center, New Orleans,  Louisiana,  70112,  United States
      Memorial Medical Center, New Orleans,  Louisiana,  70115,  United States
      Tulane University School of Medicine, New Orleans,  Louisiana,  70112,  United States
Massachusetts
      Boston Medical Center, Boston,  Massachusetts,  02118,  United States
      Cancer Research Center, Boston,  Massachusetts,  02118,  United States
Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201-1379,  United States
      Henry Ford Hospital, Detroit,  Michigan,  48202,  United States
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0752,  United States
Mississippi
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States
Missouri
      CCOP - Cancer Research for the Ozarks, Springfield,  Missouri,  65807,  United States
      St. John's Health System, Springfield,  Missouri,  65804,  United States
      St. Louis University Health Sciences Center, Saint Louis,  Missouri,  63110-0250,  United States
New York
      Herbert Irving Comprehensive Cancer Center, New York,  New York,  10032,  United States
Ohio
      CCOP - Dayton, Kettering,  Ohio,  45429,  United States
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195,  United States
      Jewish Hospital of Cincinnati, Inc., Cincinnati,  Ohio,  45236,  United States
      Miami Valley Hospital, Dayton,  Ohio,  45409,  United States
Oklahoma
      University of Oklahoma Health Sciences Center, Oklahoma City,  Oklahoma,  73190,  United States
Oregon
      CCOP - Columbia River Program, Portland,  Oregon,  97213,  United States
      Legacy Cancer Services, Portland,  Oregon,  97210,  United States
      Oregon Cancer Center, Portland,  Oregon,  97201-3098,  United States
      Providence St. Vincent Medical Center, Portland,  Oregon,  97225,  United States
Texas
      Brooke Army Medical Center, Fort Sam Houston,  Texas,  78234,  United States
      CCOP - Scott and White Hospital, Temple,  Texas,  76508,  United States
      Health Science Center, Lubbock,  Texas,  79430,  United States
      Methodist Health Care System, San Antonio,  Texas,  78229,  United States
      Scott and White Clinic, Temple,  Texas,  76508,  United States
      Texas Tech University Health Science Center, Lubbock,  Texas,  79423,  United States
      University of Texas Health Science Center at San Antonio, San Antonio,  Texas,  78284-7811,  United States
      Wilford Hall - 59th Medical Wing, Lackland Air Force Base,  Texas,  78236-5300,  United States
Utah
      Huntsman Cancer Institute, Salt Lake City,  Utah,  84112,  United States
      LDS Hospital, Salt Lake City,  Utah,  84143,  United States
Washington
      CCOP - Northwest, Tacoma,  Washington,  98405-0986,  United States
      CCOP - Virginia Mason Research Center, Seattle,  Washington,  98101,  United States
      Franciscan Health System, Tacoma,  Washington,  98401-2197,  United States
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109-1024,  United States
      Swedish Cancer Institute, Seattle,  Washington,  98104,  United States
      University of Washington Medical Center, Seattle,  Washington,  98195-6043,  United States
Canada, Ontario
      Princess Margaret Hospital, Toronto,  Ontario,  M5G 2M9,  Canada

Study chairs or principal investigators

Jeanne E. Anderson,  Study Chair,  Southwest Oncology Group   

Study ID Numbers:  CDR0000067898; SWOG-S9920
Record last reviewed:  March 2004
Last Updated:  October 13, 2004
Record first received:  June 2, 2000
ClinicalTrials.gov Identifier:  NCT00005866
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08