Trial Information

A Study of Modified Augmented BFM Therapy for Infants With Acute Lymphoblastic Leukemia

OBJECTIVES:

- Determine the feasibility of dexamethasone-based induction chemotherapy followed by
augmented Berlin-Frankfurt-Munster (BFM) consolidation chemotherapy with or without
allogeneic bone marrow transplantation in infants with previously untreated acute
lymphoblastic leukemia.

- Determine the event-free survival of patients treated with this regimen.

- Determine the clinical prognostic features associated with outcome in these patients.

- Compare the biologic characteristics of the leukemia cells with outcome in these
patients.

OUTLINE: This is a multicenter study.

Patients receive induction therapy comprising oral dexamethasone 3 times daily on days 1-14;
daunorubicin IV on days 1, 8, and 15; vincristine IV on days 1, 8, 15, and 22; and
asparaginase intramuscularly (IM) on days 4, 6, 8, 11, 13, 15, 18, 20, and 22. Patients also
receive methotrexate intrathecally (IT) on days 1, 8, and 15 (and days 4 and 22 for overt
CNS disease).

Patients with M1 or M2 marrow after induction therapy receive augmented consolidation
therapy when blood counts recover. Patients receive cyclophosphamide IV on days 1 and 29;
cytarabine IV or subcutaneously (SC) on days 2-5, 9-12, 30-33, and 37-40; oral
mercaptopurine on days 1-14 and 29-42; vincristine IV on days 15, 22, 43, and 50;
pegaspargase IM on days 15 and 43; and methotrexate IT on days 1, 8, and 15.

Patients who do not receive bone marrow transplantation (BMT) proceed to interim maintenance
#1 when blood counts recover. Patients receive methotrexate IT on days 1, 11, 22, and 32;
methotrexate IV and vincristine IV on days 1, 11, 22, 32, and 43; and pegaspargase IM on
days 2 and 23.

When blood counts recover, patients receive delayed intensification #1 comprising
vincristine IV on days 1, 8, 15, 43, and 50; doxorubicin IV on days 1, 8, and 15; oral
dexamethasone 3 times daily on days 1-7 and 15-21; pegaspargase IM on days 4 and 43;
cyclophosphamide IV on day 29; methotrexate IT on days 29 and 36; oral thioguanine on days
29-42; and cytarabine IV or SC on days 30-33 and 37-40.

When blood counts recover, patients receive interim maintenance #2 comprising vincristine as
in interim maintenance #1; methotrexate IT on day 1 and IV on days 1, 11, 22, 32, and 41;
and pegaspargase IM on days 2 and 23.

When blood counts recover, patients receive delayed intensification #2 comprising
vincristine, doxorubicin, dexamethasone, pegaspargase, cyclophosphamide, cytarabine, and
thioguanine as in intensification #1. Patients also receive methotrexate IT on days 1 and
29.

When blood counts recover, patients receive maintenance therapy comprising methotrexate IT
on day 1 and orally on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; vincristine IV
on days 1, 29, and 57; oral dexamethasone 3 times daily on days 1-5, 29-33, and 57-61; and
oral mercaptopurine daily. Treatment repeats every 84 days for 6 courses.

Patients with an allergy to pegaspargase replace it with asparaginase IM on the days after
receiving methotrexate IV during interim maintenance #1 and #2 and daily over 6 days in
place of each dose of pegaspargase during delayed intensification #1 and #2.

After augmented consolidation therapy, patients meeting the following criteria may receive
BMT in place of chemotherapy:

- In remission

- Exhibiting chromosome translocation involving 11q23 or Ph+{(9;22)}

- Available HLA-A, B, DR genotypic identical relative donor

- No uncontrolled infection

- Adequate organ function Within 3-4 weeks of consolidation therapy, patients undergoing
allogeneic BMT receive cytarabine IV over 1 hour on days -8 to -5; cyclophosphamide IV
over 30 minutes on days -7 and -6; and methylprednisolone IV twice daily on days -2 to
0. Patients also undergo total body irradiation twice daily on days -3 to 0. Patients
receive allogeneic BMT on day 0. Patients also receive cyclosporine IV every 12 hours
beginning on day -1, switching to oral when possible, and continuing until day 60.
Patients then taper cyclosporine over the next 60-120 days.

Patients are followed every 2 months for 1 year, every 3 months for 1 year, every 4 months
for 1 year, every 6 months for 1-2 years, and then annually thereafter.

PROJECTED ACCRUAL: A maximum of 20-40 patients will be accrued for this study within 2
years.