LeukemiaPhase 3NCT00002961
Chemotherapy With or Without Total-Body Irradiation Prior to Bone Marrow Transplantation in Treating Children With Acute Lymphoblastic Leukemia
A Phase 3 study testing cyclophosphamide, cyclosporine and etoposide in people with Leukemia, run by Children's Hospital of Philadelphia at 18 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Leukemia
- What is being tested?
- cyclophosphamide, cyclosporine and etoposide
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 18 sitesin 2 countries
- Study dates
- Oct 1995to Feb 2001
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
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
Trial locations and contacts
18 sites in 2 countries.
18 sites in 2 countries
United States17 sites
University of Alabama Comprehensive Cancer Center
Birmingham, Alabama, 35294
University of Chicago Cancer Research Center
Chicago, Illinois, 60637
Ireland Cancer Center
Cleveland, Ohio, 44106-5065
Palmetto Richland Memorial Hospital
Columbia, South Carolina, 29203
Nemours Children's Clinic
Jacksonville, Florida, 32207
Children's Mercy Hospital
Kansas City, Missouri, 64108
Albert B. Chandler Medical Center, University of Kentucky
Lexington, Kentucky, 40536-0084
Louisiana State University School of Medicine
New Orleans, Louisiana, 70112-2822
Tulane University School of Medicine
New Orleans, Louisiana, 70112
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Huntsman Cancer Institute
Salt Lake City, Utah, 84132
South Texas Cancer Institute
San Antonio, Texas, 78229
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78284-7811
Children's Hospital and Health Center
San Diego, California, 92123-4282
Cardinal Glennon Children's Hospital
St Louis, Missouri, 63104
Washington University Medical Center
St Louis, Missouri, 63110
All Children's Hospital
St. Petersburg, Florida, 33701
About this study
Official title: Randomized Trial of Busulfan or Total Body Irradiation Conditioning Regimens for Children With Acute Lymphoblastic Leukemia
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.
Read the 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.
- Conditions
- Leukemia
- Being tested
- cyclophosphamide, cyclosporine, etoposide, methotrexate, allogeneic bone marrow transplantation
- Keywords
- recurrent childhood acute lymphoblastic leukemia, childhood acute lymphoblastic leukemia in remission
- Medical subject headings
- Leukemia, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cyclophosphamideDrug
Also called Cytoxin
Arms A and B Day 2 and 3: Cyclophosphamide 60 mg/kg intravenously; Administer 20 mg/ml concentration over 2 hours.
cyclosporineDrug
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.
etoposideDrug
Also called Etopophos, etoposide phosphate, VP-16
Day 4 (arms A/B): 40 mg/kg over four hours intravenously
methotrexateDrug
Also called MTX
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 transplantationProcedure or surgery
Also called BMT
Bone marrow infusion given on day 0
Total Body IrradiationRadiation
Also called TBI
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)].
BusulfanDrug
Also called Myleran
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.
MesnaDrug
Also called Mesnex
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.
RadiationRadiation
Central Nervous System (CNS) therapy:
- 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-
| Study group | Role | What they receive |
|---|---|---|
| Total body irradiation | Active comparator | Total body irradiation 1200 centigray Receives: Drug: cyclophosphamide; Drug: etoposide; Procedure: allogeneic bone marrow transplantation; Radiation: Total Body Irradiation; Radiation: Radiation |
| Busulfan | Active comparator | Busulfan 16 doses Receives: Drug: cyclophosphamide; Drug: cyclosporine; Drug: etoposide; Drug: methotrexate; Procedure: allogeneic bone marrow transplantation; Drug: Busulfan; Drug: Mesna; Radiation: Radiation |
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2004 (estimated)
- Study startOct 1995
- Primary completionFeb 2001
- Study completionFeb 2001
Why it stopped: poor accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nancy Bunin, MD, Study chair, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00002961
- Sponsor's protocol ID
- 1995-9-1013
- Other IDs
- CHP-BMT-583, BMS-CHP-BMT-583, NCI-V97-1183
- Status last verified
- Oct 2013
- First submitted
- 1 Nov 1999
- Last updated
- 16 Oct 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial of Busulfan or Total Body Irradiation Conditioning Regimens for Children With Acute Lymphoblastic Leukemia
- ClinicalTrials.gov ID
- NCT00002961
- Acronym / sponsor ID
- 1995-9-1013
- Conditions
- Leukemia
- Keywords
- recurrent childhood acute lymphoblastic leukemia, childhood acute lymphoblastic leukemia in remission
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: poor accrual
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Study start
- Oct 1995
- Primary completion
- Feb 2001 (actual)
- Study completion
- Feb 2001 (actual)
- First posted
- 19 May 2004 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Total body irradiation | Active comparator | Drug: cyclophosphamide, Drug: etoposide, Procedure: allogeneic bone marrow transplantation, Radiation: Total Body Irradiation, Radiation: RadiationTotal body irradiation 1200 centigray |
| Busulfan | Active comparator | Drug: cyclophosphamide, Drug: cyclosporine, Drug: etoposide, Drug: methotrexate, Procedure: allogeneic bone marrow transplantation, Drug: Busulfan, Drug: Mesna, Radiation: RadiationBusulfan 16 doses |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cyclophosphamideAlso: CytoxinArms A and B Day 2 and 3: Cyclophosphamide 60 mg/kg intravenously; Administer 20 mg/ml concentration over 2 hours. | Drug | Busulfan, Total body irradiation |
| cyclosporinegraft 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. | Drug | Busulfan |
| etoposideAlso: Etopophos, etoposide phosphate, VP-16Day 4 (arms A/B): 40 mg/kg over four hours intravenously | Drug | Busulfan, Total body irradiation |
| methotrexateAlso: MTXmethotrexate 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. | Drug | Busulfan |
| allogeneic bone marrow transplantationAlso: BMTBone marrow infusion given on day 0 | Procedure or surgery | Busulfan, Total body irradiation |
| Total Body IrradiationAlso: TBIDay 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 | Total body irradiation |
| BusulfanAlso: MyleranConditioning 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. | Drug | Busulfan |
| MesnaAlso: MesnexDosing 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. | Drug | Busulfan |
| RadiationCentral 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- | Radiation | Busulfan, Total body irradiation |
Primary outcome
Not reported in the source record.
Results and safety
The study was stopped early (reason given: poor accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nancy Bunin, MD study chair
Children's Hospital of Philadelphia
18 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing cyclophosphamide, cyclosporine and etoposide in people with Leukemia, run by Children's Hospital of Philadelphia at 18 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Oct 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: poor accrual). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2013.