Chemotherapy With or Without Total-Body Irradiation Prior to Bone Marrow Transplantation in Treating Children With Acute Lymphoblastic Leukemia
NCT ID: NCT00002961
Last Updated: 2013-10-16
Study Results
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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TERMINATED
PHASE3
43 participants
INTERVENTIONAL
1995-10-31
2001-02-28
Brief Summary
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PURPOSE: Randomized phase III trial to compare high-dose chemotherapy with or without total-body irradiation before bone marrow transplantation in treating children with acute lymphoblastic leukemia.
Detailed Description
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OUTLINE: This is a multicenter, randomized study comparing a chemotherapy only arm, including busulfan, with a TBI containing arm. Arm I patients receive TBI on days -7, -6, and -5 given in 2 fractions daily. Arm II patients receive busulfan every 6 hours on days -8, -7, -6, and -5. Both regimens are followed by etoposide over 4 hours on day -4 and cyclophosphamide intravenously (IV) on days -3 and -2. Marrow infusion begins following a day of rest. Starting on day -1, cyclosporine IV is administered every 12 hours or by continuous infusion and continues until day 50. Methotrexate IV is administered on days 1, 3, and 6
PROJECTED ACCRUAL: A total of 230 patients will be entered into this study.
Conditions
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Keywords
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Study Design
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RANDOMIZED
TREATMENT
Study Groups
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Total body irradiation
Total body irradiation 1200 centigray
cyclophosphamide
Arms A and B Day 2 and 3: Cyclophosphamide 60 mg/kg intravenously; Administer 20 mg/ml concentration over 2 hours.
etoposide
Day 4 (arms A/B): 40 mg/kg over four hours intravenously
allogeneic bone marrow transplantation
Bone marrow infusion given on day 0
Total Body Irradiation
Day 0: Marrow Transfusion; Day 1: rest; Day 2 and 3: Cyclophosphamide 60 mg/kg; Day 4: Etopophos 40 mg/kg over four hours; Day 5,6 and 7: Total Body Irradiation (TBI) \[200 cGy twice a day (BID)\].
Radiation
Central Nervous System (CNS) therapy:
a) CNS Leukemia prior to study entry: No TBI i) No prior CNS irradiation: 2340 centigray (cGy) in 13 fractions of 180 cGy to the cranial field and 600 cGy in 200 cGy fractions to the spinal field prior to conditioning. II) \>/= 1800 cGy prior CNS irradiation: 1800 cGy to cranial field and 600 cGy spinal prior to conditioning. If prior radiation therapy (RT) doses \>3000 cGy have been administered or CNS Leukemia prior to study entry: TBI, consult with Principal Investigator (PI). Recommend: 1) no prior CNS irradiation: 600 cGy in 3 fractions to the cranial field prior to conditioning or overlapping with TBI.
Testicular Boost Irradiation: a) overt testicular leukemia at relapse: No TBI 2400 cGy in 12 fractions prior to conditioning; b) overt testicular leukemia at relapse: TBI 1200 cGy in 6 fractions over 8-10 days prior to conditioning. c) No overt testicular leukemia: 200 cGy first and last fractions of TBI-
Busulfan
Busulfan 16 doses
cyclophosphamide
Arms A and B Day 2 and 3: Cyclophosphamide 60 mg/kg intravenously; Administer 20 mg/ml concentration over 2 hours.
cyclosporine
graft vs. host disease (GVHD)prophylaxis: starting on day-1, cyclosporin 1.5 mg/kg IV every 12 hours or by continuous infusion.
When the patient tolerates adequate oral intake, cyclosporin therapy may be changed from IV to oral administration. Cyclosporin therapy should be continued at full dose until day +50. if the patient has less than Grade 2 GVHD, cyclosporin may be tapered by 5-10% weekly until completely off cyclosporin therapy.
etoposide
Day 4 (arms A/B): 40 mg/kg over four hours intravenously
methotrexate
methotrexate 15 mg/m2 IV on day +1 (do not give until 24 hours after marrow infusion), and 10mg/mg2 IV on days +3 and +6.
Methotrexate may be held after two doses for bilirubin .2 mg/dL. If serum creatinine is \>2x baseline, methotrexate will be omitted. If the presence of ascites or pleural effusion, methotrexate will be omitted.
allogeneic bone marrow transplantation
Bone marrow infusion given on day 0
Busulfan
Conditioning Regimen Arm B:
Day 0: Marrow infusion; Day 1: Rest; Day 2 and 3: Cyclophosphamide 60 mg/kg; Day 4: Etopophos 40 mg/kg over four hours; Day 5,6,7 and 8: Busulfan 0.8 mg/kg intravenous (IV) every 6 hours x 4 doses.
Patients \</= 20kg to receive busulfan 1.0 mg/kg/dose IV\*\*Busulfan oral preparation may be substituted: 1mg/kg/dose by mouth (po) for patients \>20kg and 1.25 mg/kg/dose by mouth (po) for patients \</= 20 kg.
Mesna
Dosing per institutional preference for hemorrhagic cystitis. Mesna 300 mg/m2 as a 15 minute infusion prior to each dose of cyclophosphamide, then at 3,6,9,12, 18 and 21 hours after initiation of each cyclophosphamide infusion. Alternative method of Mesna administration is 10 mg/kg prior to cyclophosphamide and 100 mg/kg/24 hours by continuous infusion.
Radiation
Central Nervous System (CNS) therapy:
a) CNS Leukemia prior to study entry: No TBI i) No prior CNS irradiation: 2340 centigray (cGy) in 13 fractions of 180 cGy to the cranial field and 600 cGy in 200 cGy fractions to the spinal field prior to conditioning. II) \>/= 1800 cGy prior CNS irradiation: 1800 cGy to cranial field and 600 cGy spinal prior to conditioning. If prior radiation therapy (RT) doses \>3000 cGy have been administered or CNS Leukemia prior to study entry: TBI, consult with Principal Investigator (PI). Recommend: 1) no prior CNS irradiation: 600 cGy in 3 fractions to the cranial field prior to conditioning or overlapping with TBI.
Testicular Boost Irradiation: a) overt testicular leukemia at relapse: No TBI 2400 cGy in 12 fractions prior to conditioning; b) overt testicular leukemia at relapse: TBI 1200 cGy in 6 fractions over 8-10 days prior to conditioning. c) No overt testicular leukemia: 200 cGy first and last fractions of TBI-
Interventions
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cyclophosphamide
Arms A and B Day 2 and 3: Cyclophosphamide 60 mg/kg intravenously; Administer 20 mg/ml concentration over 2 hours.
cyclosporine
graft vs. host disease (GVHD)prophylaxis: starting on day-1, cyclosporin 1.5 mg/kg IV every 12 hours or by continuous infusion.
When the patient tolerates adequate oral intake, cyclosporin therapy may be changed from IV to oral administration. Cyclosporin therapy should be continued at full dose until day +50. if the patient has less than Grade 2 GVHD, cyclosporin may be tapered by 5-10% weekly until completely off cyclosporin therapy.
etoposide
Day 4 (arms A/B): 40 mg/kg over four hours intravenously
methotrexate
methotrexate 15 mg/m2 IV on day +1 (do not give until 24 hours after marrow infusion), and 10mg/mg2 IV on days +3 and +6.
Methotrexate may be held after two doses for bilirubin .2 mg/dL. If serum creatinine is \>2x baseline, methotrexate will be omitted. If the presence of ascites or pleural effusion, methotrexate will be omitted.
allogeneic bone marrow transplantation
Bone marrow infusion given on day 0
Total Body Irradiation
Day 0: Marrow Transfusion; Day 1: rest; Day 2 and 3: Cyclophosphamide 60 mg/kg; Day 4: Etopophos 40 mg/kg over four hours; Day 5,6 and 7: Total Body Irradiation (TBI) \[200 cGy twice a day (BID)\].
Busulfan
Conditioning Regimen Arm B:
Day 0: Marrow infusion; Day 1: Rest; Day 2 and 3: Cyclophosphamide 60 mg/kg; Day 4: Etopophos 40 mg/kg over four hours; Day 5,6,7 and 8: Busulfan 0.8 mg/kg intravenous (IV) every 6 hours x 4 doses.
Patients \</= 20kg to receive busulfan 1.0 mg/kg/dose IV\*\*Busulfan oral preparation may be substituted: 1mg/kg/dose by mouth (po) for patients \>20kg and 1.25 mg/kg/dose by mouth (po) for patients \</= 20 kg.
Mesna
Dosing per institutional preference for hemorrhagic cystitis. Mesna 300 mg/m2 as a 15 minute infusion prior to each dose of cyclophosphamide, then at 3,6,9,12, 18 and 21 hours after initiation of each cyclophosphamide infusion. Alternative method of Mesna administration is 10 mg/kg prior to cyclophosphamide and 100 mg/kg/24 hours by continuous infusion.
Radiation
Central Nervous System (CNS) therapy:
a) CNS Leukemia prior to study entry: No TBI i) No prior CNS irradiation: 2340 centigray (cGy) in 13 fractions of 180 cGy to the cranial field and 600 cGy in 200 cGy fractions to the spinal field prior to conditioning. II) \>/= 1800 cGy prior CNS irradiation: 1800 cGy to cranial field and 600 cGy spinal prior to conditioning. If prior radiation therapy (RT) doses \>3000 cGy have been administered or CNS Leukemia prior to study entry: TBI, consult with Principal Investigator (PI). Recommend: 1) no prior CNS irradiation: 600 cGy in 3 fractions to the cranial field prior to conditioning or overlapping with TBI.
Testicular Boost Irradiation: a) overt testicular leukemia at relapse: No TBI 2400 cGy in 12 fractions prior to conditioning; b) overt testicular leukemia at relapse: TBI 1200 cGy in 6 fractions over 8-10 days prior to conditioning. c) No overt testicular leukemia: 200 cGy first and last fractions of TBI-
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
21 Years
ALL
No
Sponsors
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Children's Hospital of Philadelphia
OTHER
Responsible Party
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Principal Investigators
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Nancy Bunin, MD
Role: STUDY_CHAIR
Children's Hospital of Philadelphia
Locations
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University of Alabama Comprehensive Cancer Center
Birmingham, Alabama, United States
Children's Hospital and Health Center
San Diego, California, United States
Nemours Children's Clinic
Jacksonville, Florida, United States
All Children's Hospital
St. Petersburg, Florida, United States
University of Chicago Cancer Research Center
Chicago, Illinois, United States
Albert B. Chandler Medical Center, University of Kentucky
Lexington, Kentucky, United States
Louisiana State University School of Medicine
New Orleans, Louisiana, United States
Tulane University School of Medicine
New Orleans, Louisiana, United States
Children's Mercy Hospital
Kansas City, Missouri, United States
Cardinal Glennon Children's Hospital
St Louis, Missouri, United States
Washington University Medical Center
St Louis, Missouri, United States
Ireland Cancer Center
Cleveland, Ohio, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Palmetto Richland Memorial Hospital
Columbia, South Carolina, United States
South Texas Cancer Institute
San Antonio, Texas, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States
Huntsman Cancer Institute
Salt Lake City, Utah, United States
Alberta Children's Hospital
Calgary, Alberta, Canada
Countries
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Other Identifiers
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CHP-BMT-583
Identifier Type: OTHER
Identifier Source: secondary_id
BMS-CHP-BMT-583
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-V97-1183
Identifier Type: OTHER
Identifier Source: secondary_id
1995-9-1013
Identifier Type: -
Identifier Source: org_study_id