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.

Condition	Treatment or Intervention	Phase
L3 adult acute lymphoblastic leukemia adult Burkitt's lymphoma untreated adult acute lymphoblastic leukemia	Drug: cyclophosphamide  Drug: cytarabine  Drug: doxorubicin  Drug: etoposide  Drug: filgrastim  Drug: ifosfamide  Drug: leucovorin calcium  Drug: methotrexate  Drug: vincristine  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: radiation therapy	Phase II

Further Study Details: 

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.

Ages Eligible for Study:  16 Years and above,  Genders Eligible for Study:  Both

Criteria

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

United Kingdom, England
      Medical Research Council Clinical Trials Unit, London,  England,  NW1 2DA,  United Kingdom; Recruiting

Study chairs or principal investigators

Simon Clawson,  Study Chair,  Medical Research Council   

Study ID Numbers:  CDR0000069374; MRC-LY10; EU-20117; NCT00040690
Record last reviewed:  December 2002
Last Updated:  December 3, 2004
Record first received:  July 8, 2002
ClinicalTrials.gov Identifier:  NCT00040690
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08