Trial Information

Phase III Study of Combination Chemotherapy in Children With T Cell and Pre-B Cell Non-Hodgkin's Lymphoma

OBJECTIVES:

- Assess the event free survival at 2 and 5 years of children with T cell or pre-B cell
non-Hodgkin's lymphoma treated with a sequential induction regimen, a consolidation
regimen, a reintensification regimen, and a maintenance regimen.

- Assess the rate of local relapse at 2 and 5 years of these children after receiving
this treatment.

- Determine the toxicity of this treatment in these patients.

- Determine the overall survival of these children at 5 years after receiving this
treatment.

OUTLINE: This is a multicenter study.

Patients receive 5 weeks of induction chemotherapy consisting of prednisone IV twice a day
on days 1-28, then decreasing in dose on days 29-35; vincristine IV on days 8, 15, 22, and
29; cyclophosphamide IV over 1 hour on day 8; daunorubicin IV over 24 hours on days 15, 22,
and 29; asparaginase IV or IM on days 16, 18, 20, 23, 25, 27, 30, and 32; and methotrexate
IV over 3 hours on day 8. Patients also receive methotrexate and methylprednisolone
intrathecally (IT) on days 1, 4, 9, and 15.

Patients with a response over 50% proceed to 4-8 weeks of consolidation therapy. This
regimen consists of vincristine IV on day 15, cyclophosphamide IV over 1 hour followed by
methotrexate over 3 hours on day 1, cytarabine IV on days 2-5 and 8-11, asparaginase IV or
IM on days 16 and 23, and methotrexate IV over 3 hours on day 15. Patients also receive
methotrexate and methylprednisolone IT on days 2 and 16. Patients who achieve complete
remission after 4 weeks repeat consolidation therapy for another course.

Patients then receive 4 weeks of interphase therapy consisting of oral mercaptopurine on
days 1 and 22, methotrexate IV over 3 hours on days 1 and 15, and methotrexate and
methylprednisolone IT on days 2 and 16.

Patients with pre-B cell lymphoma then proceed to maintenance therapy. Patients with T cell
lymphoma proceed to reinduction therapy. Reinduction A is a 4 week course of chemotherapy
administered during months 1, 3, and 5 and consists of vincristine IV on day 1; methotrexate
IV over 3 hours on days 1, 8, 15, and 22; methotrexate and methylprednisolone IT on day 2;
asparaginase IM or IV on day 2; and oral mercaptopurine. Reinduction B is also a 4 week
course of therapy administered during months 2, 4, and 6. This consists of oral prednisone
twice a day on days 1-5; cytarabine subcutaneously twice a day on days 1-4; methotrexate IV
on days 1, 8, 15, and 22; and oral mercaptopurine.

Patients then proceed to maintenance therapy, which consists of methotrexate and
mercaptopurine once a week. Patients with stage I, II, or III disease continue maintenance
therapy for 18 months, while patients with stage IV disease continue this therapy for 24
months.

Patients with stage IV disease with neuromeningeal involvement receive triple intrathecal
therapy consisting of methotrexate, cytarabine, and methylprednisolone, then reinduction A
for months 1, 2, and 3, then reinduction B for months 4, 5, and 6 (if T cell lymphoma).
These patients also receive cerebral irradiation during months 4 and 5. Patients with pre-B
cell disease receive cerebral irradiation after intensification therapy.

Patients with less than 50% response after induction therapy or incomplete remission after
4-8 weeks of consolidation therapy, or who have a recurrence of disease are treated with the
"VANDA" regimen consisting of dexamethasone on days 1-5; cytarabine over 3 hours twice a day
on days 1 and 2; mitoxantrone IV over 1 hour on days 3 and 4; etoposide IV over 1 hour on
days 3-5; and asparaginase IV over 1 hour or IM on days 7, 9, 11, and 13. Patients also
receive triple intrathecal therapy (methotrexate, cytarabine, and methylprednisolone) on day
5.

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

PROJECTED ACCRUAL: A total of 200 patients will be accrued for this study within 4 years.