Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy in Treating Patients With Burkitt's Lymphoma or Burkitt's Leukemia

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	16 and over	Other	MRC-LY10 EU-20117, NCT00040690

Objectives

1. 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).
2. Determine whether cytogenetic and molecular changes are associated with or predictable from the immunophenotype of the tumor cells or patient characteristics (e.g., age).
3. Examine the relationship between t(14;18) and bcl-2 expression in patients treated with this regimen.
4. 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.
5. 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.
6. Assess further the activity of these regimens in patients with leukemic Burkitt's lymphoma.
7. Modify the chemotherapy doses in these regimens to include older patients who are often excluded from clinical trials.

Entry 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

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

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

Expected Enrollment

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.

Outcomes

Progression-free survival

Survival time

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.

Mead GM, Barrans SL, Qian W, et al.: A prospective clinicopathologic study of dose-modified CODOX-M/IVAC in patients with sporadic Burkitt lymphoma defined using cytogenetic and immunophenotypic criteria (MRC/NCRI LY10 trial). Blood 112 (6): 2248-60, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Medical Research Council Clinical Trials Unit

Simon Clawson, Protocol chair		Ph: 44-207-670-4801

Registry Information
Official Title		A Clinicopathological Study In Burkitts's And Burkitt-Like Non-Hodgkin's Lymphoma
Trial Start Date		2008-11-18
Registered in ClinicalTrials.gov		NCT00040690
Date Submitted to PDQ		2002-04-03
Information Last Verified		2007-05-23

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