Trial Information

INDUCTION INTENSIFICATION AND ALLOGENEIC BONE MARROW TRANSPLANT IN INFANT ALL: A PEDIATRIC ONCOLOGY GROUP PILOT STUDY Induction Intensification and Allogeneic Bone Marrow Transplant in Infant ALL: A Children's Oncology Group Pilot Study

OBJECTIVES:

Primary

- Assess the feasibility of intensification with two courses of high-dose methotrexate
followed by one course of cyclophosphamide/etoposide during induction and later as
consolidation in infants with newly diagnosed acute lymphoblastic leukemia.

- Determine event-free survival after shortened, intensive therapy in these patients.

- Compare event-free survival rates of infants receiving this regimen whose leukemic
blasts have or do not have translocations involving the 11q23 gene MLL.

Secondary

- Correlate the presence of minimal residual disease at completion of induction,
beginning of continuation, and at completion of therapy with patient outcome.

- Investigate the clinical prognostic features that may be associated with outcome in
infants, such as bone marrow blast content at day 8, white blood cell count, and age.

- Correlate biologic characteristics of the leukemia cells at diagnosis (protocol
POG-9900) with outcome in patients treated with this regimen.

- Characterize patterns of gene expression associated with host and disease
characteristics and treatment response in patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients are stratified according to participating
center and presence of CNS disease (yes vs no).

Patients receive induction chemotherapy comprising vincristine IV on days 1, 8, and 15; oral
prednisone three times a day on days 1-21; daunorubicin IV over 30 minutes on days 1-2;
cyclophosphamide IV over 30 minutes every 12 hours on days 3-4; and asparaginase
intramuscularly (IM) on days 4, 6, 8, 10, 12, 15, 17, and 19. Patients also receive triple
intrathecal therapy comprising methotrexate, hydrocortisone, and cytarabine on days 1, 8,
and 15 and filgrastim (G-CSF) subcutaneously (SC) or IV beginning on day 5 and continuing
until day 20, regardless of blood counts.

Patients receive induction intensification chemotherapy comprising high-dose methotrexate IV
over 24 hours; triple intrathecal therapy as per induction therapy on days 22 and 29; and
leucovorin calcium IV every 6 hours for 2 doses beginning 42 hours after start of high-dose
methotrexate and then orally every 6 hours for 3 doses. Patients also receive etoposide IV
over 2 hours and cyclophosphamide IV over 30 minutes on days 36-40. Patients receive G-CSF
SC or IV beginning on day 41 and continuing until blood counts recover.

Patients achieving morphologic remission and recovery of blood counts while off G-CSF for 48
hours receive reinduction chemotherapy comprising the same regimen as in induction therapy
with the exception of asparaginase IM beginning on day 1 (week 8) and continuing every
Monday, Wednesday, and Friday for a total of 8 doses and triple intrathecal therapy on days
1 and 15 only (weeks 8 and 10). Patients receive G-CSF SC or IV beginning on day 5 and
continuing until blood counts recover.

After blood count recovery, patients receive consolidation chemotherapy comprising triple
intrathecal therapy as per induction therapy on day 1 (week 11); high-dose methotrexate IV
over 24 hours on weeks 8 and 12; and leucovorin calcium IV every 6 hours for 2 doses
beginning 42 hours after start of high-dose methotrexate and then orally every 6 hours for 3
doses. Patients also receive etoposide IV over 2 hours followed by cyclophosphamide IV over
30 minutes on days 15-19 (week 13). Patients receive G-CSF SC or IV beginning on day 20 and
continuing until blood counts recover. On days 29-31 (week 15), patients receive high-dose
cytarabine IV over 3 hours every 12 hours for 4 doses and asparaginase IM 6 hours after
completion of high-dose cytarabine. Patients receive G-CSF beginning 24 hours after
completion of asparaginase and continuing until blood counts recover.

Patients achieving morphologic remission and blood count recovery while off G-CSF for 48
hours receive continuation therapy comprising vincristine IV on day 1; oral prednisone three
times a day on days 1-5; and triple intrathecal therapy on day 1 (weeks 18 and 22). Patients
also receive methotrexate IM once a week and oral mercaptopurine daily on weeks 19-21, 23,
and 24. On week 25, patients receive etoposide IV over 2 hours daily followed by
cyclophosphamide IV over 30 minutes daily on days 1-5 and G-CSF SC or IV beginning on day 6
and continuing until blood counts recover. Patients receive an additional course of
continuation therapy on weeks 28-35. On weeks 38-48, patients receive another identical
course of continuation therapy with the exclusion of the etoposide and cyclophosphamide
combination regimen.

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

PROJECTED ACCRUAL: Approximately 58-104 patients will be accrued for this study within 2.1
years.