Trial Information

ALINC #17 Treatment for Patients With Low Risk Acute Lymphoblastic Leukemia: A Pediatric Oncology Group Phase III Study

OBJECTIVES:

- Compare the efficacy and toxicity of short methotrexate infusion vs longer infusion in
patients with low-risk acute lymphoblastic leukemia.

- Compare the efficacy of these regimens of methotrexate, with or without multidrug
intensification, in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
genetics (stratum 1: trisomy 4/10 but not TEL/AML1 vs stratum 2: TEL/AML1 with or without
trisomy 4/10).

All patients receive induction therapy (weeks 1-4) on another protocol (POG-9900).

Stratum 1

- Consolidation therapy begins on week 5. Patients are randomized to arm I or II.

- Arm I: Patients receive methotrexate (MTX) IV over 24 hours on day 1 and oral
leucovorin calcium (CF) every 6 hours for 3 doses beginning 42 hours after
initiation of MTX infusion during weeks 7, 10, 13, 16, and 19.

- Arm II: Patients receive MTX IV over 4 hours on day 1 and oral CF as in arm I
during weeks 7, 10, 13, 16, and 19.

- Patients in arms I and II also receive MTX intrathecally (IT) on weeks 7, 10, 13, 16,
19, and 22; oral mercaptopurine (6-MP) daily on weeks 5-24; oral dexamethasone (DM)
twice daily on days 1-7 of weeks 8 and 17; and vincristine (VCR) IV on day 1 of weeks
8, 9, 17, and 18.

Stratum 2

- Consolidation therapy begins on week 5 and delayed intensification therapy begins on
week 16. Patients are randomized to delayed intensification or no delayed
intensification. Patients randomized to no delayed intensification are then randomized
to consolidation therapy on arm I or II. Patients randomized to delayed intensification
are then randomized to arm III or IV. Patients with trisomy 4/10 are not randomized to
arms III and IV.

- Arm III: Patients receive MTX IV and CF as in arm I on weeks 7, 10, 13, 24, 27,
and 30.

- Arm IV: Patients receive MTX IV and CF as in arm II on weeks 7, 10, 13, 24, 27,
and 30.

- Patients in arms III and IV also receive oral 6-MP daily on weeks 5-13 and then
beginning on week 24 and continuing until the end of consolidation; MTX IT on weeks 7,
10, 13, 16, 20, 21, and 30; oral DM twice daily on days 1-7 of weeks 8, 16-18, and 28;
VCR IV on day 1 of weeks 8, 9, 16-18, 28, and 29; pegaspargase intramuscularly on week
16; daunorubicin IV on day 1 of weeks 16-18; cyclophosphamide IV on day 1 of week 20;
cytarabine IV or subcutaneously on days 2-5 of weeks 20 and 21; and oral thioguanine
daily on days 1-14 of weeks 20 and 21.

All patients then receive continuation therapy beginning on week 25 for arms I and II and
week 33 for arms III and IV and continuing until week 130 for all arms.

Continuation

- Arms I and II: Patients receive oral 6-MP daily on weeks 25-130; oral DM twice a day on
days 1-7 and VCR IV on days 1 and 8 during weeks 25, 41, 57, 73, 89, and 105; oral MTX
weekly on weeks 25-130 (except during weeks of IT MTX); and MTX IT on weeks 25, 37, 49,
61, 73, 85, 97, and 109.

- Arms III and IV: Patients receive oral 6-MP daily on weeks 33-130; oral DM twice a day
on days 1-7 and VCR IV on days 1 and 8 during weeks 41, 57, 73, 89, and 105; oral MTX
weekly on weeks 33-130 (except during weeks of IT MTX); and MTX IT on weeks 37, 49, 61,
73, 85, 97, and 109.

Patients are followed every 2 months for 2 years, every 3 months for 1 year, every 6 months
for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total 902 patients will be accrued for this study within 3.22 years.