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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

Phase 3
Completed
Conditions
Myelodysplastic Syndromes
Leukemia
Interventions
Procedure: allogeneic bone marrow transplantation
Radiation: radiation therapy
Registration Number
NCT00005866
Lead Sponsor
SWOG Cancer Research Network
Brief 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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
240
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
treatmentallogeneic bone marrow transplantation-
treatmentcyclophosphamide-
treatmentcyclosporine-
treatmentradiation therapy-
treatmentbusulfan-
treatmentmethotrexate-
Primary Outcome Measures
NameTimeMethod
Event-free survivalevery 6 months after stem cell infusion until death or 5 years
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (66)

Good Samaritan Medical Center

🇺🇸

Phoenix, Arizona, United States

Arizona Cancer Center

🇺🇸

Tucson, Arizona, United States

University of Arkansas for Medical Sciences

🇺🇸

Little Rock, Arkansas, United States

Alta Bates Comprehensive Cancer Center

🇺🇸

Berkeley, California, United States

Cancer Center and Beckman Research Institute, City of Hope

🇺🇸

Duarte, California, United States

Scripps Clinic

🇺🇸

La Jolla, California, United States

USC/Norris Comprehensive Cancer Center and Hospital

🇺🇸

Los Angeles, California, United States

Jonsson Comprehensive Cancer Center, UCLA

🇺🇸

Los Angeles, California, United States

St. Joseph Hospital - Orange

🇺🇸

Orange, California, United States

Chao Family Comprehensive Cancer Center

🇺🇸

Orange, California, United States

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Good Samaritan Medical Center
🇺🇸Phoenix, Arizona, United States

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