Trial Information

Treatment of Acute Lymphoblastic Leukemia in Children

- Children with acute lymphoblastic leukemia are treated somewhat differently depending
on the relative risk of the leukemia recurring. Patients will be separated into
"Standard Risk" and "High Risk".

- The treatment program for both groups is separated into 4 phases. The phases of
treatment are induction, central nervous system (CNS) therapy, intensification and
continuation.

- The induction phase of therapy lasts for about one month and its purpose is to kill all
detectable leukemia cells. Patients in both groups will receive the following
medication: prednisone, vincristine, doxorubicin, methotrexate, leucovorin,
asparaginase, cytarabine (ARA-C), and hydrocortisone. Patients in the "Hight Risk"
group will also receive dexrazoxane.

- Patients whose leukemia is found to have a specific genetic abnormality involving a
gene on chromosome 11 (known as MLL gene) will have a MLL intensification phase which
begins after complete remission and lasts about 1 month. The drugs involved in MLL
intensification are: vincristine, methotrexate, leucovorin, hydrocortisone, cytarabine
and L-asparaginase.

- CNS therapy begins immediately after the end of induction therapy, after remission is
documented. This phase of treatment should last 3 weeks and includes a series of
spinal taps with the instillation of anti-leukemia drugs. Four spinal taps will be
performed over a two-week period. Both groups will receive vincristine,
6-mercaptopurine and methotrexate/cytarabine/hydrocortisone. Patients in the "High
Risk" group will also receive doxorubicin with dexrazoxane.

- Radiation therapy will also be delivered to patients in the "High Risk" group during
the CNS therapy phase. Radiation will be given in 8 daily treatments. The total dose
of radiation used during this study is lower than what has been used in the past to
help reduce side effects without increasing the risk of relapse.

- The intensification phase begins after the CNS therapy ends and lasts for 30 weeks.
This phase is intended to further reduce the number of leukemia cells in the body and
consists of cycles of chemotherapy repeated every three weeks with weekly shots of
asparaginase. The drugs administered to both groups during this phase are: prednisone
or dexamethasone, vincristine,6-mercaptopurine, methotrexate, E. coli asparaginase and
cytarabine. Patients in the "High Risk" group will also receive doxorubicin and
dexrazoxane.

- The continuation phase begins after the completion of the intensification phase and the
goal is to eradicate all leukemia from the body. It consists of cycles of chemotherapy
repeated every 3 weeks and is continued until the patient has been in remission for 2
years. The drugs administered during this phase are vincristine, prednisone or
dexamethasone, 6-mercaptopurine, methotrexate and cytarabine.

- During this trial there are two randomizations, each is between the "standard"
treatment and the "investigational" treatment. One randomization involves the drug E.
coli L-asparaginase and two ways of dosing this drug. One way is to give the same
standard dose of the drug that has been administered for years. The other way is to
start with a lower dose and measure the amount of the drug in the blood every 3 weeks
adjusting the dose as necessary. The goal of doing this is to maintain adequate drug
levels with lower doses in the hope the it may reduce some side effects of the drug.

- The second randomization involves the drugs prednisone and dexamethasone. Both drugs
have been used in the past to help treat ALL but it is not known if there is a
difference between the two drugs, especially in terms of side effects. Patients will
be randomized to either receive dexamethasone or prednisone.

- Throughout the study blood tests, urine tests, spinal taps, and bone marrow tests will
be performed to monitor the disease status, side effects from medications and other
complications from therapy.

- Quality of life questionnaires will also be performed by the patient (if older than 8),
parent and patient's clinician.