Combination Chemotherapy in Treating Patients With Burkitt's Lymphoma or Burkitt's Leukemia
Combination Chemotherapy in Treating Patients With Burkitt's Lymphoma or Burkitt's Leukemia
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing
 so they stop growing or die. Combining more than one drug may kill more tumor cells.

 PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating
 patients who have Burkitt's lymphoma or Burkitt's leukemia.
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.
DISEASE CHARACTERISTICS:

 -  Diagnosis of diffuse B-cell lymphoma in a nodal or an extranodal site

 -  CD20 and CD79 positive

 -  100% expression of Ki67 (MIB1) in all of the tumor cells OR

 -  Diagnosis of bone marrow replacement/leukemia comprising mature B-cell lymphoma

 -  sIg and CD19 positive

 -  CD34 and Tdt negative

 -  Patients in the low-risk group must meet at least 3 of the following criteria:

 -  Normal lactate dehydrogenase (LDH) level

 -  WHO performance status 0-1

 -  Ann Arbor stage I or II

 -  No more than 1 extranodal site (e.g., bone marrow, gastrointestinal tract, or
 CNS)

 -  Patients in the high-risk group must meet at least 2 of the following criteria:

 -  Raised LDH level

 -  WHO performance status 2-4

 -  Ann Arbor stage III or IV

 -  More than 1 extranodal site

 PATIENT CHARACTERISTICS:

 Age:

 -  16 and over

 Performance status:

 -  See Disease Characteristics

 Life expectancy:

 -  Not specified

 Hematopoietic:

 -  See Disease Characteristics

 Hepatic:

 -  See Disease Characteristics

 Renal:

 -  Not specified

 Other:

 -  No mental or physical status that would preclude study

 -  No other disease or prior malignancy that would preclude study

 -  HIV negative

 -  Not pregnant

 -  Negative pregnancy test

 -  Fertile patients must use effective contraception

 PRIOR CONCURRENT THERAPY:

 Biologic therapy:

 -  Not specified

 Chemotherapy:

 -  No prior chemotherapy except 1 course of preinduction chemotherapy (e.g., CHOP
 [cyclophosphamide, doxorubicin, vincristine, and prednisone] or a related regimen)

 Endocrine therapy:

 -  Not specified

 Radiotherapy:

 -  No prior radiotherapy

 Surgery:

 -  Not specified