Trial Information

A Multicenter Study of Treatment Protocol for Childhood Acute Lymphoblastic Leukemia in China, 2008.

OBJECTIVES:

Primary

- Compare the incidence of marrow suppression with 2 methods of maintenance treatment in
children with acute lymphoblastic leukemia.

- Compare the incidence of liver toxicity with 2 methods of maintenance treatment in
these patients.

Secondary

- Determine any difference in infection rates and related hospitalizations in these
patients.

OUTLINE: This is a multicenter study. Patients are stratified according to risk (high vs
intermediate vs standard), age in years (0 to 5 vs 6 to 9 vs 10 to 17), and sex.

- Patients with standard-risk disease:

- Induction therapy: Patients receive prednisolone IV or orally three times daily on
days 1-7; oral dexamethasone three times daily on days 8-28; asparaginase IV over
1 hour or intramuscularly once on days 8, 11, 14, 17, 20, 23, 26, and 29;
vincristine IV once on days 8, 15, 22, and 29; daunorubicin hydrochloride IV over
1 hour on days 8 and 15; and methotrexate intrathecally (IT) once on days 1, 15,
and 33.

- Early intensification (EI) therapy: Patients receive cyclophosphamide IV over 1
hour on day 36, cytarabine IV continuously on days 38-41 and 45-48, oral
mercaptopurine once daily on days 36-50, and methotrexate IT on days 38 and 45.

- Consolidation therapy: Two weeks after completing EI therapy, patients receive
oral mercaptopurine once daily on days 1-56 and methotrexate IV over 24 hours and
IT on days 8, 22, 36, and 50.

- Delayed intensification (DI) therapy:

- DI/a: Patients receive dexamethasone orally or IV three times daily on days
1-7 and 15-21, doxorubicin hydrochloride IV over 1 hour on days 1, 8, and 15;
vincristine IV on days 1, 8, and 15; and asparaginase subcutaneously (SC) or
IV over 1 hour on days 1, 4, 8, and 11.

- DI/b: Patients receive cyclophosphamide IV over 1 hour on day 29, cytarabine
IV continuously on days 31-34 and 38-41, oral thioguanine once daily on days
29-42, and methotrexate IT on days 31 and 38.

- Maintenance therapy: Patients are randomized to one of two treatment arms.
Patients who do not consent for randomization receive conventional therapy (arm
I).

- Arm I (conventional): Patients receive oral mercaptopurine and oral
methotrexate on days 1-56, dexamethasone IV on days 1-5 and 29-33,
vincristine IV on days 1 and 29, and methotrexate IT on day 50. Treatment
repeats every 8 weeks for up to 8 courses for girls or 11 courses for boys.

- Arm II (intervention): Patients receive oral mercaptopurine once daily on
days 8-28 and 36-56; oral methotrexate once on days 8,15, 22, 36, 43, and 50;
dexamethasone IV on days 1-5 and 29-33; and vincristine IV on days 1 and 29.
Patients also receive methotrexate IT on day 1, every 8 weeks, for 8 courses.

- Patients with intermediate-risk disease:

- Induction therapy: Patients receive prednisolone, dexamethasone, and asparaginase
as in standard-risk induction therapy. Patients also receive vincristine IV and
daunorubicin hydrochloride IV over 1 hour on days 8, 15, 22, and 29; methotrexate
IT on day 1; and triple intrathecal therapy (TIT; high-dose methotrexate,
cytarabine, hydrocortisone sodium succinate) on days 15 and 33.

- First EI therapy: Patients receive cyclophosphamide, cytarabine, and
mercaptopurine as in standard-risk EI. Patients also receive TIT on day 38.

- Second EI therapy: Beginning 2 weeks after completing first EI, patients receive
cyclophosphamide over 1 hour on day 1, oral mercaptopurine on days 1-14,
cytarabine IV on days 3-6 and 10-13, and TIT on day 3.

- Consolidation therapy: Beginning 2 weeks after completing second EI, patients
receive mercaptopurine as in standard-risk consolidation therapy. Patients also
receive methotrexate IV over 24 hours and TIT on days 8, 22, 36, and 50.

- First DI therapy: Patients receive treatment as in standard-risk DI.

- Interim maintenance therapy: Patients receive oral mercaptopurine and oral
methotrexate on days 1-56.

- Second DI therapy: Patients receive DI/a and D1/b (without methotrexate) as in
standard-risk DI. Patients also receive TIT on days 31 and 38.

- Maintenance therapy: Patients are randomized to 1 of 2 treatment arms:

- Arm I (conventional): Patients receive mercaptopurine, methotrexate,
dexamethasone, and vincristine as in standard-risk maintenance therapy arm I.
Patients also receive TIT on day 50. Treatment repeats every 8 weeks for up
to 8 courses for girls or 11 courses for boys.

- Arm II (intervention): Patients receive treatment as in standard-risk
maintenance therapy arm II.

- Patients with high-risk disease:

- Induction therapy: Patients receive treatment as in intermediate-risk induction
therapy.

- First EI therapy: Patients receive treatment as in intermediate-risk first EI.

- Second EI therapy: Patients receive treatment as in intermediate-risk second EI.

- Consolidation therapy (interval between blocks is 2 weeks):

- Block 1: Patients receive dexamethasone orally or IV three times daily on
days 1-5, vincristine IV on days 1 and 6, high-dose methotrexate IV over 24
hours on day 1, cyclophosphamide IV over 1 hour twice daily on days 2-4,
cytarabine IV over 3 hours twice on day 5, asparaginase IV over 2 hours on
days 6 and 11, and TIT on day 1.

- Block 2: Patients receive dexamethasone, high-dose methotrexate,
asparaginase, and TIT as in block 1. Patients also receive vindesine IV twice
daily on days 1 and 6, ifosfamide IV over 1 hour twice daily on days 2-4, and
daunorubicin hydrochloride IV over 24 hours on day 5.

- Block 3: Patients receive dexamethasone and asparaginase as in block 1.
Patients also receive high-dose cytarabine IV over 3 hours twice daily on
days 1 and 2, etoposide IV over 1 hour five times on days 3-5, and TIT on day
5.

- Blocks 1-3 are then repeated once. Patients then proceed to delayed
intensification therapy.

- Delayed intensification therapy: Patients receive dexamethasone orally or IV three
times daily on days 1-7 and 15-21; doxorubicin hydrochloride IV and vincristine IV
on days 8, 15, 22, and 29; and asparaginase IV on days 8, 11, 15, and 18. Patients
also receive cyclophosphamide IV on day 36, cytarabine IV on days 38-41 and 45-48,
thioguanine IV on days 36-49, and TIT on days 38 and 45.

- Maintenance therapy: Patients receive oral mercaptopurine and oral methotrexate
once daily on days 1-14, cyclophosphamide over 1 hour and cytarabine over 1 hour
once between days 15-21, oral dexamethasone two or three times daily for 5 days
between days 29-35, vincristine IV on day 29, and TIT on day 22. Treatment repeats
every 4 weeks. After 10 courses, patients no longer receive TIT. After 12 courses,
patients no longer receive cyclophosphamide and cytarabine. At this time patients
continue mercaptopurine and methotrexate on days 1-21. After 20 courses, patients
no longer receive dexamethasone or vincristine. At this time, patients continue
mercaptopurine and methotrexate on days 1-28. Females receive up to 17 courses and
males up to 23 courses.

Some patients may also undergo radiotherapy or stem cell transplantation.