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Busulfan Compared With Cyclophosphamide in Patients Undergoing Total-Body Irradiation Plus Peripheral Stem Cell Transplantation for Advanced Myelodysplastic Syndrome or Related Acute Myeloid Leukemia

This study is ongoing, but not recruiting participants.

Sponsors and Collaborators: Southwest Oncology Group
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00005866
  Purpose

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 Intervention Phase
Leukemia
Myelodysplastic Syndromes
Drug: busulfan
Drug: cyclophosphamide
Drug: cyclosporine
Drug: methotrexate
Procedure: allogeneic bone marrow transplantation
Procedure: radiation therapy
Phase III

MedlinePlus related topics:   Bone Marrow Transplantation    Cancer    Leukemia, Adult Acute    Leukemia, Adult Chronic    Leukemia, Childhood   

Drug Information available for:   Cyclophosphamide    Methotrexate    Cyclosporin    Cyclosporine    Busulfan   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment, Randomized
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)

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:   June 2000

Detailed 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.

  Eligibility
Ages Eligible for Study:   16 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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

  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005866

Show 66 study locations  Show 66 Study Locations

Sponsors and Collaborators
Southwest Oncology Group
National Cancer Institute (NCI)

Investigators
Study Chair:     Jeanne E. Anderson, MD     Katmai Oncology Group    
  More Information


Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site
 

Study ID Numbers:   CDR0000067898, SWOG-S9920
First Received:   June 2, 2000
Last Updated:   July 23, 2008
ClinicalTrials.gov Identifier:   NCT00005866
Health Authority:   United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
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

Study placed in the following topic categories:
Cyclosporine
Precancerous Conditions
Clotrimazole
Refractory anemia
Chronic myelomonocytic leukemia
Miconazole
Cyclophosphamide
Leukemia, Myeloid, Acute
Cyclosporins
Leukemia
Preleukemia
Anemia, Refractory
Neoplasm Metastasis
Methotrexate
Acute myeloid leukemia, adult
Acute myelocytic leukemia
Myelodysplastic syndromes
Hematologic Diseases
Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes
Myelodysplasia
Tioconazole
Anemia
Acute myelogenous leukemia
Leukemia, Myeloid
Folic Acid
Busulfan
Anemia, Refractory, with Excess of Blasts
Bone Marrow Diseases

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Reproductive Control Agents
Pathologic Processes
Syndrome
Therapeutic Uses
Antifungal Agents
Abortifacient Agents
Alkylating Agents
Dermatologic Agents
Nucleic Acid Synthesis Inhibitors
Disease
Neoplasms by Histologic Type
Enzyme Inhibitors
Folic Acid Antagonists
Abortifacient Agents, Nonsteroidal
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents

ClinicalTrials.gov processed this record on December 03, 2008




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