Trial Information

Treatment of Childhood Acute Lymphoblastic Leukemia

- 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.