Trial Information

A Clinicopathological Study In Burkitts's And Burkitt-Like Non-Hodgkin's Lymphoma

OBJECTIVES:

- Describe the morphology, phenotype, and cytogenetics, using fresh tumor tissue (when
possible), in patients with Burkitt's or Burkitt-like lymphoma/leukemia treated with
the CODOX-M chemotherapy regimen (cyclophosphamide, vincristine, doxorubicin, and
methotrexate) alone or alternating with the IVAC chemotherapy regimen (ifosfamide,
etoposide, and cytarabine).

- Determine whether cytogenetic and molecular changes are associated with or predictable
from the immunophenotype of the tumor cells or patient characteristics (e.g., age).

- Examine the relationship between t(14;18) and bcl-2 expression in patients treated with
this regimen.

- Determine whether the presence of specific cytogenetic and molecular changes, in
particular the presence of t(14;18) and t(8;14), is associated with an adverse outcome
(progression-free and overall survival) in patients treated with this regimen.

- Assess the activity of the alternating CODOX-M/IVAC chemotherapy regimens using a lower
dose of methotrexate (compared to the UKLG LY06 trial) in these patients.

- Assess further the activity of these regimens in patients with leukemic Burkitt's
lymphoma.

- Modify the chemotherapy doses in these regimens to include older patients who are often
excluded from clinical trials.

OUTLINE: This is a multicenter study. Patients with low-risk disease are assigned to group
A, while patients with high-risk disease are assigned to group B.

Group A (low-risk group):

- Patients receive 3 courses of the CODOX-M chemotherapy regimen comprising
cyclophosphamide IV on days 1-5, vincristine IV on days 1 and 8, doxorubicin IV on day
1, and methotrexate (MTX) IV over 24 hours on day 10. Patients over age 65 receive
reduced-dose MTX on day 10. All patients receive leucovorin calcium (CF) IV once at
hour 36 after initiation of MTX infusion, once every 3 hours between hours 36-48, and
continuing once every 6 hours until blood levels of MTX are safe. Patients also receive
filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 13 and continuing
until blood counts recover.

- During all 3 courses of the CODOX-M regimen, patients receive CNS prophylaxis
comprising cytarabine (ARA-C) intrathecally (IT) on days 1 and 3, MTX IT on day 15, and
oral CF (24 hours after IT MTX) on day 16.

Group B (high-risk group):

- Patients receive the CODOX-M chemotherapy regimen (as above) alternating with the IVAC
chemotherapy regimen (as defined below) for a total of 4 courses given in the following
sequence: CODOX-M, IVAC, CODOX-M, and IVAC. The IVAC chemotherapy regimen comprises
ifosfamide (IFF) IV over 1 hour and etoposide IV over 1 hour on days 1-5 and ARA-C IV
over 3 hours on days 1 and 2. Patients over age 65 receive reduced-dose IFF and ARA-C.
Patients also receive G-CSF SC once daily beginning on day 7 and continuing until blood
counts recover.

- During IVAC, patients without CNS disease receive MTX IT on day 5 and oral CF (24 hours
after MTX). Patients with proven CNS disease receive intensified IT therapy throughout
the first two courses of CODOX-M/IVAC chemotherapy.

For patients in group B with CNS disease at diagnosis, radiotherapy is only considered in
the presence of a cerebral mass documented by CT scan or MRI. Patients in group A or B who
develop isolated CNS recurrence (documented by malignant CSF pleocytosis, cranial nerve
palsies, or both) at any time after the first course of study therapy receive the same CNS
treatment (as above) as patients with proven CNS disease in addition to whole brain
irradiation for 3 weeks.

Patients are followed monthly for 4 months, every 2 months for 8 months, every 3 months for
1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A minimum of 120 patients (30 with low-risk disease and 90 with high-risk
disease) will be accrued for this study within approximately 3-4 years.