Trial Information

Multicentric Study for the Treatment of Children With Acute Lymphoblastic Leukemia

OBJECTIVES:

- Determine the dose of daunorubicin hydrochloride that is equivalent to 30 mg/m² of
doxorubicin hydrochloride in pediatric patients with acute lymphoblastic leukemia
(ALL).

- Determine whether it is possible to reduce therapy in pediatric patients with low-risk
ALL and a PVA (prednisolone-vincristine-asparaginase) score of 3+4 without loss of
efficacy.

- Investigate the role of single nucleotide polymorphisms of infection defense gene for
infectious complications during therapy in these patients.

- Reduce neurological complications by reducing doses of intrathecal methotrexate.

- Reduce allergic reactions against asparaginase (ASP) by using pegaspargase after E.
coli ASP.

OUTLINE: This is a randomized, multicenter study.

- Prephase: Patients are randomized to 1 of 3 treatment arms.

- Arm I: Patients receive doxorubicin hydrochloride IV once.

- Arm II: Patients receive daunorubicin hydrochloride IV once.

- Arm III: Patients receive daunorubicin hydrochloride IV once at a higher dose than
in arm II.

- Induction phase: All patients receive vincristine IV 4 times weekly, daunorubicin
hydrochloride IV 3 times weekly, and oral prednisolone daily for 4 weeks.

- Intensive phase: Patients are stratified according to risk (low vs high).

- Low-risk disease*: Patients receive 4 courses of methotrexate IV and asparaginase
intramuscularly (IM).

- High-risk disease*: Patients receive 6 courses of cyclophosphamide IV,
methotrexate IV, and asparaginase IM.

All patients also receive methotrexate IV, teniposide IV, cytarabine IV, high-dose
cytarabine IV, and asparaginase IM after completion of the above regimen.

- CNS phase: All patients receive intrathecal (IT) methotrexate for 3 doses and oral
mercaptopurine for 4 weeks. Patients with T-cell acute lymphoblastic leukemia or
patients who have blasts in cerebrospinal fluid at diagnosis or whose WBC > 200/nL at
diagnosis OR whose WBC between 100-200/nL at diagnosis and blasts > 1/nL after prephase
chemotherapy undergo cranial irradiation.

- Reinduction phase: Patients are stratified according to risk (low vs high)

- Low-risk disease*: Patients receive 2 courses of doxorubicin hydrochloride IV,
vincristine IV, and oral dexamethasone; pegaspargase IM once; and 1 course of
cyclophosphamide IV, cytarabine IV, and oral thioguanine.

- High-risk disease*: Patients receive 4 courses of doxorubicin hydrochloride IV,
vincristine IV, and oral dexamethasone; pegaspargase IM twice; and 2 courses of
cyclophosphamide IV, cytarabine IV, and oral thioguanine.

- Maintenance phase: All patients receive oral mercaptopurine daily and methotrexate IV
once weekly for up to 2 years after diagnosis.

NOTE: *In addition to those defined in Disease Characteristics, patients who do not achieve
remission after induction phase are treated as high-risk disease, patients who achieve
remission after induction phase are treated as low-risk disease

PROJECTED ACCRUAL: A total of 550 patients will be accrued for this study.