Treatment of Childhood Acute Lymphoblastic Leukemia

December 20, 2007 updated by: Dana-Farber Cancer Institute
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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment

491

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Hamilton, Ontario, Canada
        • McMaster University
    • Quebec
      • Montreal, Quebec, Canada
        • Laval University
      • Montreal, Quebec, Canada
        • Sainte Justine Hosptial
  • Puerto Rico
      • Santurce, Puerto Rico, 00912
        • San Jorge Children's Hospital
  • United States
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Clinic
    • Maine
      • Lewiston, Maine, United States, 04240
        • Maine Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02115
        • Children's Hospital Boston
    • New York
      • New York, New York, United States, 10029
        • Mt. Sinai Medical Center
      • Rochester, New York, United States, 14627
        • University of Rochester

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
-To evaluate the efficacy and safety of doxorubicin with or without dexrazoxane
-To determine the efficacy of hyperfractionated radiation plus standard intrathecal chemotherapy compared with intensive intrathecal chemotherapy alone in standard risk patients.
-To compare the relative efficacy and toxicity of E.coli and Erwinia asparaginase
-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

Outcome Measure
-To compare randomized treatment groups using health-related quality of life analyses.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dana-Farber Cancer Institute

Collaborators

Boston Children's Hospital

Investigators

  • Principal Investigator: Stephen E. Sallan, MD, Dana-Farber Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 1996

Primary Completion (Actual)

September 1, 2006

Study Completion (Actual)

September 1, 2006

Study Registration Dates

First Submitted

September 9, 2005

First Submitted That Met QC Criteria

September 9, 2005

First Posted (Estimate)

September 14, 2005

Study Record Updates

Last Update Posted (Estimate)

December 28, 2007

Last Update Submitted That Met QC Criteria

December 20, 2007

Last Verified

December 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 95-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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