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

NCT ID: NCT00005866

Last Updated: 2015-03-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

240 participants

Study Classification

INTERVENTIONAL

Study Start Date

2000-02-29

Study Completion Date

2006-03-31

Brief Summary

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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

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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.

Conditions

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Leukemia Myelodysplastic Syndromes

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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treatment

Group Type EXPERIMENTAL

busulfan

Intervention Type DRUG

arm 1: 0.44 mg/kg every 6 hours, IV over 2 hours, day -7 to -4

cyclophosphamide

Intervention Type DRUG

arm 2: 60 mg/kg every 24 hrs for 2 doses, IV over 2 hrs, days -5 and -4

cyclosporine

Intervention Type DRUG

both arms per published schedule

methotrexate

Intervention Type DRUG

GVHD: 15 mg/m2 day 1, 10 mg/m2 day 3, 6 and 11 by IV

allogeneic bone marrow transplantation

Intervention Type PROCEDURE

day 0

radiation therapy

Intervention Type RADIATION

both arms: 1200 cGy total dose (6 x 200 fractions)

Interventions

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busulfan

arm 1: 0.44 mg/kg every 6 hours, IV over 2 hours, day -7 to -4

Intervention Type DRUG

cyclophosphamide

arm 2: 60 mg/kg every 24 hrs for 2 doses, IV over 2 hrs, days -5 and -4

Intervention Type DRUG

cyclosporine

both arms per published schedule

Intervention Type DRUG

methotrexate

GVHD: 15 mg/m2 day 1, 10 mg/m2 day 3, 6 and 11 by IV

Intervention Type DRUG

allogeneic bone marrow transplantation

day 0

Intervention Type PROCEDURE

radiation therapy

both arms: 1200 cGy total dose (6 x 200 fractions)

Intervention Type RADIATION

Eligibility Criteria

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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
Minimum Eligible Age

16 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jeanne E. Anderson, MD

Role: STUDY_CHAIR

Katmai Oncology Group

Locations

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Good Samaritan Medical Center

Phoenix, Arizona, United States

Site Status

Arizona Cancer Center

Tucson, Arizona, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Alta Bates Comprehensive Cancer Center

Berkeley, California, United States

Site Status

Cancer Center and Beckman Research Institute, City of Hope

Duarte, California, United States

Site Status

Scripps Clinic

La Jolla, California, United States

Site Status

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, United States

Site Status

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, United States

Site Status

St. Joseph Hospital - Orange

Orange, California, United States

Site Status

Chao Family Comprehensive Cancer Center

Orange, California, United States

Site Status

Sutter Cancer Center

Sacramento, California, United States

Site Status

University of California Davis Cancer Center

Sacramento, California, United States

Site Status

Stanford University Medical Center

Stanford, California, United States

Site Status

Northern California Cancer Specialists Medical Clinic

Walnut Creek, California, United States

Site Status

University of Colorado Cancer Center

Denver, Colorado, United States

Site Status

Cancer Research Center of Hawaii

Honolulu, Hawaii, United States

Site Status

Queen's Medical Center

Honolulu, Hawaii, United States

Site Status

St. Francis Medical Center

Honolulu, Hawaii, United States

Site Status

Mountain States Tumor Institute

Boise, Idaho, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

CCOP - Wichita

Wichita, Kansas, United States

Site Status

Cancer Center of Kansas - Wichita

Wichita, Kansas, United States

Site Status

Albert B. Chandler Medical Center, University of Kentucky

Lexington, Kentucky, United States

Site Status

Lucille Parker Markey Cancer Center, University of Kentucky

Lexington, Kentucky, United States

Site Status

Louisiana State University School of Medicine

New Orleans, Louisiana, United States

Site Status

MBCCOP - LSU Health Sciences Center

New Orleans, Louisiana, United States

Site Status

Tulane University School of Medicine

New Orleans, Louisiana, United States

Site Status

Memorial Medical Center

New Orleans, Louisiana, United States

Site Status

Louisiana State University Health Sciences Center - Shreveport

Shreveport, Louisiana, United States

Site Status

Boston Medical Center

Boston, Massachusetts, United States

Site Status

Cancer Research Center

Boston, Massachusetts, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

St. John's Health System

Springfield, Missouri, United States

Site Status

CCOP - Cancer Research for the Ozarks

Springfield, Missouri, United States

Site Status

St. Louis University Health Sciences Center

St Louis, Missouri, United States

Site Status

Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Site Status

Jewish Hospital of Cincinnati, Inc.

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Site Status

Miami Valley Hospital

Dayton, Ohio, United States

Site Status

CCOP - Dayton

Kettering, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Oregon Cancer Center

Portland, Oregon, United States

Site Status

Legacy Cancer Services

Portland, Oregon, United States

Site Status

CCOP - Columbia River Program

Portland, Oregon, United States

Site Status

Providence St. Vincent Medical Center

Portland, Oregon, United States

Site Status

Brooke Army Medical Center

Fort Sam Houston, Texas, United States

Site Status

Wilford Hall - 59th Medical Wing

Lackland Air Force Base, Texas, United States

Site Status

Texas Tech University Health Science Center

Lubbock, Texas, United States

Site Status

Health Science Center

Lubbock, Texas, United States

Site Status

Methodist Health Care System

San Antonio, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

CCOP - Scott and White Hospital

Temple, Texas, United States

Site Status

Scott and White Clinic

Temple, Texas, United States

Site Status

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

LDS Hospital

Salt Lake City, Utah, United States

Site Status

CCOP - Virginia Mason Research Center

Seattle, Washington, United States

Site Status

Swedish Cancer Institute

Seattle, Washington, United States

Site Status

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status

University of Washington Medical Center

Seattle, Washington, United States

Site Status

Franciscan Health System

Tacoma, Washington, United States

Site Status

CCOP - Northwest

Tacoma, Washington, United States

Site Status

Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status

Countries

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United States Canada

Other Identifiers

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S9920

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA032102

Identifier Type: NIH

Identifier Source: secondary_id

View Link

S9920

Identifier Type: -

Identifier Source: org_study_id

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