Trial Information

ALinC 17: Continuous Intensification for Very High Risk Acute Lymphocytic Leukemia (A.L.L.): A Pediatric Oncology Group Pilot Study

OBJECTIVES: I. Determine the feasibility of administering a new combination of agents during
postinduction consolidation therapy in children with very high risk acute lymphocytic
leukemia (VHR-ALL). II. Assess the tolerance of patients in remission of VHR-ALL for
postconsolidation therapy with continuous intensification.

OUTLINE: Patients receive induction therapy on weeks 1-4. This consists of oral prednisone
three times a day on days 1-28; vincristine IV on days 1, 8, 15, and 22; daunorubicin IV on
days 8, 15, and 22; and asparaginase 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 and 3 disease
also receive methotrexate IT on days 15 and 22. Patients who achieve M2 bone marrow on day
29 receive oral prednisone three times a day 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 or M3 on day 43, then patient is off study. Patients
proceed to consolidation therapy on weeks 5-25. This consists of high dose methotrexate IV
over 24 hours on weeks 6, 8, 16, and 18, followed by leucovorin calcium IV or orally every 6
hours for 5 doses; oral mercaptopurine on weeks 6-9 and 16-19; cytarabine IV over 6 hours
followed by idarubicin IV over 15 minutes for 4 days; and filgrastim (G-CSF) subcutaneously
(SQ) beginning on day 5 and continuing for about 10-14 days on weeks 10 and 20. Patients
receive etoposide IV over 1 hour followed by cyclophosphamide IV over 10 minutes for 5 days
and G-CSF SQ beginning on day 6 for 10-14 days on weeks 13 and 23. Methotrexate IT is
administered on weeks 6, 8, 13, 16, 18, and 23. Patients then proceed to continuous
intensification therapy during weeks 26-61. Patients receive vincristine IV, daunorubicin
IV, and methotrexate IT on day 1, and oral dexamethasone twice a day on days 1-7 on weeks
26, 32, 38, 44, 50, and 56. Patients also receive high dose cytarabine IV over 1 hour, every
12 hours, for 4 doses, followed by asparaginase IM 3 hours after the last dose of
cytarabine, on weeks 27, 33, 39, 45, 51, and 57. Oral mercaptopurine and methotrexate IM are
administered on day 1 during weeks 29, 31, 35, 37, 41, 43, 47, 49, 53, 55, 59, and 61.
Patients receive etoposide IV over 1-2 hours followed by cyclophosphamide IV during weeks
30, 36, 42, 48, 54, and 60. Patients then proceed to continuation therapy during weeks
62-126. Vincristine IV and cyclophosphamide IV are administered on weeks 62-65, 70-73,
78-81, 86-89, 94-97, 102-105, 110-113, and 118-121. Patients also receive oral dexamethasone
twice a day for 7 days on weeks 62, 70, 78, 86, 94, 102, 110, and 118, and cytarabine IV on
weeks 63, 65, 71, 73, 79, 81, 87, 89, 95, 97, 103, 105, 111, 113, 119, and 121. Oral
mercaptopurine is administered daily during weeks 66-69, 74-77, 82-85, 90-93, 98-101,
106-109, 114-117, and 122-125 and methotrexate IM on weeks 66-69, 74-77, 82-85, 90-93,
98-101, 106-109, 114-117, and 122-125. Methotrexate IT is administered during weeks 62, 70,
78, 86, 94, 102, 110, and 118. Patients who are CNS 3 at diagnosis receive whole brain
irradiation beginning at week 62 along with the first course of continuation therapy. These
patients do not receive any methotrexate IT after week 62. 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,
then annually thereafter.

PROJECTED ACCRUAL: A total of 38 patients will be accrued for this study within 12 months.