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Chemotherapy With or Without Total-Body Irradiation Prior to Bone Marrow Transplantation in Treating Children With Acute Lymphoblastic Leukemia

Primary Purpose

Leukemia

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
cyclophosphamide
cyclosporine
etoposide
methotrexate
allogeneic bone marrow transplantation
Total Body Irradiation
Busulfan
Mesna
Radiation
Sponsored by
Children's Hospital of Philadelphia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring recurrent childhood acute lymphoblastic leukemia, childhood acute lymphoblastic leukemia in remission

Eligibility Criteria

undefined - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Histologically confirmed childhood acute lymphoblastic leukemia (ALL) in second hematologic remission or greater who have relapsed: On therapy OR Within one year of discontinuation of therapy OR Greater than 1 year from discontinuation of high risk intensive therapy (matched sibling donor only) Patients with central nervous system or testicular relapse: Occurred within 18 months of diagnosis OR Following prophylactic or therapeutic cranial irradiation T cell disease with isolated central nervous system (CNS) or bone marrow relapse at any time Patients in first remission with greater than 4 weeks to achieve remission or with high risk features such as: t(4,11) t(9,22) Hypodiploidy Patients under 12 months of age in first remission with any of the following features at diagnosis: CALLA (CD10) negative white blood count (WBC) at least 100,000/mm3 Day 14 M2 or M3 bone marrow CNS disease PATIENT CHARACTERISTICS: Age: 21 and under Performance status: Not specified Life expectancy: Not specified Hematopoietic: Not specified Hepatic: No active hepatitis B or C Bilirubin no greater than 1.5 times normal Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) less than 2.5 times normal Renal: Creatinine no greater than 1.5 times normal OR Creatinine clearance at least 65 mL/min Cardiovascular: Shortening fraction greater than 27% by echocardiogram OR Ejection fraction greater than 47% by radionuclide angiogram Pulmonary: [1] forced expiratory volume at one second (FEV1)/forced vital capacity (FVC) greater than 60% For uncooperative children: No evidence of dyspnea at rest No exercise intolerance Pulse oximetry greater than 94% Other: No active infection No occult untreated infection HIV negative Not eligible for Children's Cancer Group (CCG) or Pediatric Oncology Group (POG) transplant study Donor criteria: Genotypically matched sibling or phenotypically matched family member (bone marrow or peripheral blood stem cells may be used) One antigen mismatched related donor Matched or one antigen mismatched unrelated donor Cord blood (genotypic or phenotypic match or one antigen mismatch) Matched sibling or phenotypically matched family member peripheral stem cells PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Not specified Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified

Sites / Locations

  • University of Alabama Comprehensive Cancer Center
  • Children's Hospital and Health Center
  • Nemours Children's Clinic
  • All Children's Hospital
  • University of Chicago Cancer Research Center
  • Albert B. Chandler Medical Center, University of Kentucky
  • Louisiana State University School of Medicine
  • Tulane University School of Medicine
  • Children's Mercy Hospital
  • Cardinal Glennon Children's Hospital
  • Washington University Medical Center
  • Ireland Cancer Center
  • Children's Hospital of Philadelphia
  • Palmetto Richland Memorial Hospital
  • South Texas Cancer Institute
  • University of Texas Health Science Center at San Antonio
  • Huntsman Cancer Institute
  • Alberta Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Total body irradiation

Busulfan

Arm Description

Total body irradiation 1200 centigray

Busulfan 16 doses

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 1, 1999
Last Updated
October 14, 2013
Sponsor
Children's Hospital of Philadelphia
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1. Study Identification

Unique Protocol Identification Number
NCT00002961
Brief Title
Chemotherapy With or Without Total-Body Irradiation Prior to Bone Marrow Transplantation in Treating Children With Acute Lymphoblastic Leukemia
Official Title
Randomized Trial of Busulfan or Total Body Irradiation Conditioning Regimens for Children With Acute Lymphoblastic Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
October 2013
Overall Recruitment Status
Terminated
Why Stopped
poor accrual
Study Start Date
October 1995 (undefined)
Primary Completion Date
February 2001 (Actual)
Study Completion Date
February 2001 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital of Philadelphia

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Radiation therapy uses high-energy x-rays to damage cancer cells. Combining chemotherapy, radiation therapy, and bone marrow transplantation may kill more cancer cells. 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
OBJECTIVES: I. Compare the efficacy of a busulfan containing conditioning regimen versus a total body irradiation (TBI) containing regimen for children with acute lymphoblastic leukemia (ALL) undergoing allogeneic bone marrow transplantation. II. Compare relapse rate between a chemotherapy only regimen versus a total body irradiation containing regimen for children with ALL. III. Assess and compare the acute and chronic neuropsychological effects of bone marrow transplantation (BMT) in children undergoing BMT with busulfan or TBI conditioning regimens. IV. Assess and compare the cardiac, pulmonary and growth effects of BMT in children undergoing this conditioning regimen. V. Assess the relationship between plasma busulfan levels and relapse and toxicity. VI. Assess and compare minimal residual disease patterns by quantitative polymerase chain reaction (PCR) in patients receiving busulfan or TBI conditioning regimens. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia
Keywords
recurrent childhood acute lymphoblastic leukemia, childhood acute lymphoblastic leukemia in remission

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Allocation
Randomized
Enrollment
43 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Total body irradiation
Arm Type
Active Comparator
Arm Description
Total body irradiation 1200 centigray
Arm Title
Busulfan
Arm Type
Active Comparator
Arm Description
Busulfan 16 doses
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
Cytoxin
Intervention Description
Arms A and B Day 2 and 3: Cyclophosphamide 60 mg/kg intravenously; Administer 20 mg/ml concentration over 2 hours.
Intervention Type
Drug
Intervention Name(s)
cyclosporine
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
etoposide
Other Intervention Name(s)
Etopophos, etoposide phosphate, VP-16
Intervention Description
Day 4 (arms A/B): 40 mg/kg over four hours intravenously
Intervention Type
Drug
Intervention Name(s)
methotrexate
Other Intervention Name(s)
MTX
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
allogeneic bone marrow transplantation
Other Intervention Name(s)
BMT
Intervention Description
Bone marrow infusion given on day 0
Intervention Type
Radiation
Intervention Name(s)
Total Body Irradiation
Other Intervention Name(s)
TBI
Intervention Description
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)].
Intervention Type
Drug
Intervention Name(s)
Busulfan
Other Intervention Name(s)
Myleran
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Mesna
Other Intervention Name(s)
Mesnex
Intervention Description
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.
Intervention Type
Radiation
Intervention Name(s)
Radiation
Intervention Description
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-

10. Eligibility

Sex
All
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed childhood acute lymphoblastic leukemia (ALL) in second hematologic remission or greater who have relapsed: On therapy OR Within one year of discontinuation of therapy OR Greater than 1 year from discontinuation of high risk intensive therapy (matched sibling donor only) Patients with central nervous system or testicular relapse: Occurred within 18 months of diagnosis OR Following prophylactic or therapeutic cranial irradiation T cell disease with isolated central nervous system (CNS) or bone marrow relapse at any time Patients in first remission with greater than 4 weeks to achieve remission or with high risk features such as: t(4,11) t(9,22) Hypodiploidy Patients under 12 months of age in first remission with any of the following features at diagnosis: CALLA (CD10) negative white blood count (WBC) at least 100,000/mm3 Day 14 M2 or M3 bone marrow CNS disease PATIENT CHARACTERISTICS: Age: 21 and under Performance status: Not specified Life expectancy: Not specified Hematopoietic: Not specified Hepatic: No active hepatitis B or C Bilirubin no greater than 1.5 times normal Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) less than 2.5 times normal Renal: Creatinine no greater than 1.5 times normal OR Creatinine clearance at least 65 mL/min Cardiovascular: Shortening fraction greater than 27% by echocardiogram OR Ejection fraction greater than 47% by radionuclide angiogram Pulmonary: [1] forced expiratory volume at one second (FEV1)/forced vital capacity (FVC) greater than 60% For uncooperative children: No evidence of dyspnea at rest No exercise intolerance Pulse oximetry greater than 94% Other: No active infection No occult untreated infection HIV negative Not eligible for Children's Cancer Group (CCG) or Pediatric Oncology Group (POG) transplant study Donor criteria: Genotypically matched sibling or phenotypically matched family member (bone marrow or peripheral blood stem cells may be used) One antigen mismatched related donor Matched or one antigen mismatched unrelated donor Cord blood (genotypic or phenotypic match or one antigen mismatch) Matched sibling or phenotypically matched family member peripheral stem cells PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Not specified Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nancy Bunin, MD
Organizational Affiliation
Children's Hospital of Philadelphia
Official's Role
Study Chair
Facility Information:
Facility Name
University of Alabama Comprehensive Cancer Center
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Children's Hospital and Health Center
City
San Diego
State/Province
California
ZIP/Postal Code
92123-4282
Country
United States
Facility Name
Nemours Children's Clinic
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
All Children's Hospital
City
St. Petersburg
State/Province
Florida
ZIP/Postal Code
33701
Country
United States
Facility Name
University of Chicago Cancer Research Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Albert B. Chandler Medical Center, University of Kentucky
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536-0084
Country
United States
Facility Name
Louisiana State University School of Medicine
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112-2822
Country
United States
Facility Name
Tulane University School of Medicine
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Children's Mercy Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Cardinal Glennon Children's Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63104
Country
United States
Facility Name
Washington University Medical Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Ireland Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106-5065
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Palmetto Richland Memorial Hospital
City
Columbia
State/Province
South Carolina
ZIP/Postal Code
29203
Country
United States
Facility Name
South Texas Cancer Institute
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
University of Texas Health Science Center at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78284-7811
Country
United States
Facility Name
Huntsman Cancer Institute
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Alberta Children's Hospital
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2T 5C7
Country
Canada

12. IPD Sharing Statement

Learn more about this trial

Chemotherapy With or Without Total-Body Irradiation Prior to Bone Marrow Transplantation in Treating Children With Acute Lymphoblastic Leukemia

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