Trial Information

ALinC 17: Protocol for Patients With Newly Diagnosed High Risk Acute Lymphoblastic Leukemia (ALL) - Evaluation of the Augmented BFM Regimen: A Phase III Study

OBJECTIVES:

- Determine whether augmented BFM therapy is superior to ALinc 14/15 therapy in patients
with newly diagnosed high-risk acute lymphoblastic leukemia.

- Determine whether minimal residual disease after induction therapy is predictive of an
inferior prognosis in this patient population.

- Determine the correlation between event-free survival, minimal residual disease, and
early response in this patient population treated with this multiple drug regimen.

OUTLINE: Patients are stratified by CNS or testicular disease (yes vs no).

- Induction therapy (weeks 1-5): Patients receive oral prednisone 3 times daily on days
1-29; vincristine IV on days 1, 8, 15, and 22; daunorubicin IV on days 8, 15, 22; and
asparaginase intramuscularly (IM) on days 2, 5, 8, 12, 15, and 19. Patients also
receive methotrexate intrathecally (IT) on days 1 and 8. Patients with CNS 2 or 3
disease also receive methotrexate IT on days 15 and 22.

Patients with M1 bone marrow proceed to consolidation therapy. Patients achieving M2 bone
marrow on day 29 receive oral prednisone 3 times daily on days 29-42; vincristine IV and
daunorubicin IV over 15 minutes on days 29 and 36; and asparaginase IM on days 29, 32, 36,
and 39. If bone marrow is M3 on day 29 or M2 on day 43, then patient is off study.

- Consolidation therapy (weeks 6-14): Patients receive cyclophosphamide IV over 30
minutes on days 1 and 29; cytarabine subcutaneously (SC) or IV on days 2-5, 9-12,
30-33, and 37-40; oral mercaptopurine daily on days 1-14 and 29-42; vincristine IV on
days 15, 22, 43, and 50; asparaginase IM on days 15, 17, 19, 22, 24, 26, 43, 45, 47,
50, 52, and 54; and methotrexate IT on days 1, 15, 29, and 43.

Patients then proceed to interim maintenance and delayed intensification on weeks 15-46.
Courses repeat every 16 weeks.

- Maintenance I and II (weeks 15-22 and 31-38): Patients receive vincristine IV and
methotrexate IV on days 1, 11, 21, 31, and 41; asparaginase IM on days 2, 12, 22, 32,
and 42; and methotrexate IT on days 1 and 31.

- Delayed Intensification (weeks 23-36 and 39-42): Patients receive vincristine IV on
days 57, 64, and 71; methotrexate IT on day 57; oral dexamethasone 2-3 times daily on
days 57-63 and 71-77; doxorubicin IV over 15 minutes 3 times weekly on days 57, 64, and
71; and asparaginase IM on days 60, 62, 64, 67, 69, and 71.

- Delayed Intensification-Reconsolidation (weeks 27-30 and 43-46): Patients receive oral
thioguanine on days 85-98; methotrexate IT on day 85; cyclophosphamide IV over 30
minutes on day 85; cytarabine IV or SC on days 86-89 and 93-96; asparaginase IM on days
99, 101, 103, 106, 108, and 110; and vincristine IV on days 99 and 106.

- Continuation therapy (weeks 47-130): Patients receive vincristine IV on days 1, 29, and
57; oral dexamethasone twice daily for 5 consecutive days on days 1-5, 29-33, and
57-61; oral mercaptopurine on days 1-84; oral methotrexate on days 8, 15, 22, 29, 36,
43, 50, 57, 64, 71, and 78; and methotrexate IT on day 1.

Patients with CNS 3 disease or who are within 24 months of diagnosis with an initial WBC ≥
100,000/mm^3 undergo whole brain radiotherapy (omit or discontinue mercaptopurine and IT
methotrexate) on day 1. Testicular radiotherapy also begins on day 1.

Patients may receive oral methotrexate on day 1 of each course (if IT methotrexate is not
administered).

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 of 260 patients will be accrued for this study within 3.1 years.