Trial Information

A Randomized Study of Two Methods of CNS Prophylaxis in Patients With Acute Lymphoblastic Leukemia

OBJECTIVES: I. Compare the efficacy and toxicity of cranial radiation vs triple intrathecal
chemotherapy plus high dose systemic cytarabine for prophylaxis of CNS disease in children
with acute lymphoblastic leukemia. II. Compare the overall survival rates of these patients
after these treatments.

OUTLINE: This is a randomized, multicenter study for approved centers in India only. All
patients receive induction therapy and then are randomized to one of two treatment arms.
Patients assigned to arm I receive high dose cytarabine and no cranial radiation and
patients assigned to arm II receive cranial radiation and no high dose cytarabine. Induction
1: Patients receive vincristine IV on days 1, 8, 15, 22, and 29, oral prednisone on days
1-28, triple intrathecal therapy (methotrexate, hydrocortisone, and cytarabine; TIT) on days
1, 8, 15, and 22, asparaginase IM every other day on days 2-20, and daunorubicin IV on days
8, 15, and 29. Patients who achieve remission proceed to randomization. Arm I: Induction 2:
Patients receive oral mercaptopurine daily on days 1-7 and 22-28, cytarabine IV over 3 hours
every 12 hours for 4 doses on days 1-2 and 22-23, cyclophosphamide IV on days 1 and 22, and
TIT on days 8 and 29. Induction 1 is repeated, then patients proceed to consolidation when
blood counts have recovered sufficiently. Consolidation: Induction 2 is repeated, then
patients proceed to maintenance when blood counts have recovered sufficiently. Maintenance
1: Patients receive vincristine IV and daunorubicin IV on day 1; oral prednisone on days
1-7; asparaginase IM on days 1, 3, 5, and 7; oral methotrexate once a week beginning on day
15 and skipping every 4th week, for a total of 12 weeks; oral mercaptopurine beginning on
day 15 for 3 weeks out of 4, for a total of 12 weeks; and TIT on days 1 and 36. Maintenance
2: Patients receive cytarabine IV over 3 hours every 12 hours for 4 doses on days 1-2,
cyclophosphamide IV over 30 minutes on day 1, and methotrexate, mercaptopurine, and TIT on
days 8 and 36. A total of 6 maintenance courses are administered, alternating maintenance 1
and 2. Arm II: Induction 2: Patients receive oral mercaptopurine daily on days 1-7 and
15-21, cyclophosphamide IV over 30 minutes on days 1 and 15, and intrathecal methotrexate on
days 1, 8, 15, and 22. Patients then receive cranial radiation daily on days 4-12. Induction
1 is repeated, then patients proceed to consolidation after blood counts have recovered
sufficiently. Consolidation: Patients receive cyclophosphamide IV over 30 minutes on days
1-15, vincristine IV on days 1 and 15, oral mercaptopurine daily on days 1-7 and 15-21, and
cytarabine subcutaneously every 12 hours for 6 doses on days 1-3 and 15-17. Patients proceed
to maintenance when blood counts recover sufficiently. Maintenance: Same as maintenance 1 in
arm I, excluding TIT. A total of 6 courses are administered. All patients are followed
monthly for the first 6 months, then every other month for the next 6 months, every 3 months
for the next 2 years, every 6 months for the next 5 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 1100 patients (550 per arm) will be accrued for this study
within 5 years.