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

Leukemia Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00005866
• Other study ID #: S9920
• Secondary ID: S9920U10CA032102
• Status: Completed
• Phase: Phase 3
• First received: June 2, 2000
• Last updated: March 5, 2015
• Start date: February 2000
• Est. completion date: March 2006

Study information

• Verified date: March 2015
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 240
• Est. completion date: March 2006
• Est. primary completion date: March 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years to 55 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• busulfan
arm 1: 0.44 mg/kg every 6 hours, IV over 2 hours, day -7 to -4
• cyclophosphamide
arm 2: 60 mg/kg every 24 hrs for 2 doses, IV over 2 hrs, days -5 and -4
• cyclosporine
both arms per published schedule
• methotrexate
GVHD: 15 mg/m2 day 1, 10 mg/m2 day 3, 6 and 11 by IV

Procedure:
• allogeneic bone marrow transplantation
day 0

Radiation:
• radiation therapy
both arms: 1200 cGy total dose (6 x 200 fractions)

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free survival		every 6 months after stem cell infusion until death or 5 years	No