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Treatment of Childhood Acute Lymphoblastic Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00165087
Recruitment Status : Terminated (Terminated by IRB for continuing review)
First Posted : September 14, 2005
Last Update Posted : December 28, 2007
Boston Children's Hospital
Information provided by:
Dana-Farber Cancer Institute

Brief Summary:
The purpose of this study is to reduce the side-effects and discomfort of anti-leukemia therapy, to attain long-term control of the disease and to hopefully eradicate it.

Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia Drug: asparaginase (E. Coli) Drug: asparaginase (Erwina) Drug: dexrazoxane Drug: doxorubicin Procedure: cranial radiation (once daily fractionation) Procedure: cranial radiation (twice-daily fractionation) Procedure: Intrathecal chemotherapy without radiation Phase 3

Detailed Description:
  • Children with acute lymphoblastic leukemia (ALL) are treated somewhat differently depending upon on the relative risk of the leukemia recurring. For this study they are classified into "Standard Risk", "High Risk" and "Infant/High Risk".
  • The treatment for patients in the "Standard Risk" and "High Risk" groups consists of three phases of therapy: induction treatment; prevention of brain and spinal cord leukemia (CNS treatment); and intensification/continuation chemotherapy.
  • The treatment for patients in the "Infant/High Risk" group consists of four phases of therapy: induction treatment; infant intensification therapy; intensification/continuation chemotherapy; and CNS treatment.
  • The induction treatment consists of a combination of chemotherapy drugs whose purpose is to kill all detectable leukemia cells. This process usually requires a least one month and includes six anti-leukemia drugs. These drugs are: vincristine, doxorubicin, methotrexate, cytosine arabinoside, asparaginase and steroids (methylprednisolone or prednisone).
  • After the induction phase, "Infant/High Risk" patients will receive a highly intensive month of treatment (infant intensification) . Drugs used during this month include high-dose methotrexate, asparaginase, 6-mercaptopurine and high dose cytosine arabinoside (ARA-C).
  • CNS treatment begins during induction therapy but is intensified during the second and third month after diagnosis. Treatment for all patients will include a series of spinal taps with the instillation of anti-leukemia drugs, including cytosine arabinoside and methotrexate and with or without hydrocortisone (depending upon randomization).
  • All high risk patients (those in both "High Risk" and "Infant/High Risk") as well as some standard risk patients will receive radiation treatment to the brain. Radiation therapy will either be given in either "conventional" treatments (once daily for 10 days), or "hyperfractionated" treatments (twice daily at half doses for 10 days). Total dose of radiation is 1800 cGy.
  • Intensification and continuation therapy, begins 4-5 weeks after diagnosis for "Standard Risk" and "High Risk" groups and 4-5 weeks after infant intensification in "Infant/High Risk" group. This phase of treatment continues until the completion of two years of treatment. Patients in the "Standard Risk" group will receive five anti-leukemia drugs (vincristine, prednisone, methotrexate, asparaginase, and 6-mercaptopurine). Patients in "High Risk" and "Infant/High Risk" will receive six anti-leukemia drugs (vincristine, prednisone, doxorubicin, methotrexate, asparaginase and 6-mercaptopurine).
  • All patients will be able to participate in a randomization comparing two types of asparaginase, E.coli and Erwinia. Patients will be randomized to receive either once weekly E.coli or once-weekly Erwinia during the Intensification phase, each given for a total of 20 weeks.
  • Patients in the "Standard Risk" group are able to participate in an additional randomization. Standard risk patients will be randomized to receive one of two different regimens designed to prevent central nervous system leukemia, either 1)radiation therapy (given twice daily) with chemotherapy in the spinal fluid every 18 weeks, or 2) intensive chemotherapy in the spinal fluid alone without radiation.
  • Patients in the "High Risk" and "Infant/High Risk" groups are able to participate in two randomizations in addition to the asparaginase randomization. The first will be to assess whether the drug dexrazoxane prevents heart damage caused by doxorubicin without affecting risk of relapse. Patients will be randomized to receive either doxorubicin alone or doxorubicin with dexrazoxane during the induction, CNS and intensification phases. The second randomization will compare the relative efficacy and toxicity of different cranial radiation schedules. Patients will be randomized to receive radiation in either once daily or twice daily fractions.
  • Blood and bone marrow samples will be collected to learn more about the biology of leukemia. These samples will also be used to test minimal residual disease levels to learn if these levels help predict risk of relapse.
  • Quality of life questionnaires will also be performed by the parents of patients, by children over eight, and by the child's clinician.

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Study Type : Interventional  (Clinical Trial)
Enrollment : 491 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment of Childhood Acute Lymphoblastic Leukemia
Study Start Date : January 1996
Actual Primary Completion Date : September 2006
Actual Study Completion Date : September 2006

Primary Outcome Measures :
  1. -To evaluate the efficacy and safety of doxorubicin with or without dexrazoxane
  2. -To determine the efficacy of hyperfractionated radiation plus standard intrathecal chemotherapy compared with intensive intrathecal chemotherapy alone in standard risk patients.
  3. -To compare the relative efficacy and toxicity of E.coli and Erwinia asparaginase
  4. -To compare the relative efficacy and toxicity of cranial radiation delivered in once-daily versus twice-daily fractions in high risk patinets.

Secondary Outcome Measures :
  1. -To compare randomized treatment groups using health-related quality of life analyses.

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Acute lymphoblastic leukemia, excluding known mature B-cell ALL
  • < 18 years of age
  • Patients who are leukopheresed or exchanged are eligible for study only after completion of the pheresis or exchange transfusion
  • Absence of a t(8,14) (q24; q32), t (8,22), t(2,8)
  • Total bilirubin < 1.4mg/dl

Exclusion Criteria:

  • Known HIV positive
  • Prior steroid therapy within 30 days of diagnosis
  • Septic shock
  • Ongoing intracranial hemorrhage
  • Clinical evidence of CNS or lung leukostasis

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00165087

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United States, Louisiana
Ochsner Clinic
New Orleans, Louisiana, United States, 70121
United States, Maine
Maine Medical Center
Lewiston, Maine, United States, 04240
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, New York
Mt. Sinai Medical Center
New York, New York, United States, 10029
University of Rochester
Rochester, New York, United States, 14627
Canada, Ontario
McMaster University
Hamilton, Ontario, Canada
Canada, Quebec
Laval University
Montreal, Quebec, Canada
Sainte Justine Hosptial
Montreal, Quebec, Canada
Puerto Rico
San Jorge Children's Hospital
Santurce, Puerto Rico, 00912
Sponsors and Collaborators
Dana-Farber Cancer Institute
Boston Children's Hospital
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Principal Investigator: Stephen E. Sallan, MD Dana-Farber Cancer Institute
Publications of Results:
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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ClinicalTrials.gov Identifier: NCT00165087    
Obsolete Identifiers: NCT00004034
Other Study ID Numbers: 95-001
First Posted: September 14, 2005    Key Record Dates
Last Update Posted: December 28, 2007
Last Verified: December 2007
Keywords provided by Dana-Farber Cancer Institute:
childhood ALL
standard risk
high risk
infant/high risk
Additional relevant MeSH terms:
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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cardiotonic Agents
Protective Agents
Physiological Effects of Drugs
Antimitotic Agents
Mitosis Modulators