Doxorubicin Hydrochloride Liposome and Rituximab With Combination Chemotherapy in Treating Patients With Newly Diagnosed Burkitt's Lymphoma or Burkitt-Like Lymphoma

• Response rate: complete remission rate [ Time Frame: every 6 months up to two years after treatment completion ] [ Designated as safety issue: No ]
  Response rate will be accessed by CT scans every six months up to two years following completion of treatment
  
  
• Overall response rate: disease free and overall survival [ Time Frame: every six months up to two years following treatment completion ] [ Designated as safety issue: No ]
  Overall response rate (including disease free and overall survival)will be assessed by CT scans every six months up to two years following treatment completion
  
  

• Safety of Rituximab plus Magrath regimen in HIV negative and HIV positive subjects [ Time Frame: Regimen A prior to cycles 1 and 3; Regimen B prior to cycles 2 and 4; 30 days after completion of treatment ] [ Designated as safety issue: Yes ]
  adverse events will be assessed as follows: Regimen A prior to cycles 1 and 3; Regimen B prior to cycles 2 and 4; 30 days after completion of treatment
  
  
• Safety of using doxil in place of adriamycin [ Time Frame: Regimen A prior to cycles 1 and 3 and 30 days after completion of treatment ] [ Designated as safety issue: Yes ]
  Adverse events will be assessed as follows: Regimen A prior to cycles 1 and 3 and 30 days after completion of treatment
  
  
• Safety of using lower intravenous methotrexate dosing [ Time Frame: Regimen A prior to cycles 1 and 3 and 30 days after completion of treatment ] [ Designated as safety issue: Yes ]
  Adverse events will be assessed as follows: Regimen A prior to cycles 1 and 3 and 30 days after completion of treatment
  
  

OBJECTIVES:

Primary

• Determine the overall response rate (complete remission, complete remission undetermined, and partial remission) in HIV-negative or HIV-positive patients with newly diagnosed Burkitt's or Burkitt-like lymphoma treated with doxorubicin hydrochloride liposome and rituximab as part of the Magrath regimen.

Secondary

• Determine the complete remission rate in patients treated with this regimen.
• Determine progression-free and overall survival at 2 years in patients treated with this regimen.
• Determine the safety of adding rituximab to the standard Magrath regimen in these patients.
• Determine the safety of using doxorubicin hydrochloride liposome in place of doxorubicin hydrochloride in these patients.
• Determine correlative levels of rituximab and doxorubicin hydrochloride liposome in cerebrospinal fluid and peripheral blood.

OUTLINE: This is a multicenter study. Patients are stratified according to risk category (low risk vs high risk). Patients are assigned to 1 of 2 treatment regimens according to stratum.

• Regimen A (low-risk disease with no CNS involvement): Patients receive R-CODOX-M chemotherapy comprising rituximab IV over 2-4 hours on days 0 and 8; doxorubicin hydrochloride liposome IV over 30 minutes on day 1; vincristine IV on days 1 and 8; cyclophosphamide IV over 1 hour on days 1-5; and high-dose methotrexate (MTX) IV over 24 hours on day 10. Patients also receive leucovorin calcium IV beginning 36 hours after the start of MTX infusion and continuing every 6 hours until blood levels of MTX are safe. Patients also receive filgrastim (G-CSF) subcutaneously (SC) once daily on days 4-8 in courses 1 and 3 and on days 6 and 7 in course 2. Beginning on day 12, daily G-CSF dosing resumes until blood counts recover. Patients receive CNS prophylaxis comprising cytarabine intrathecally (IT) on day 1 and MTX IT on day 3. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
• Regimen B (high-risk disease with or without CNS involvement): Patients receive R-CODOX-M chemotherapy with leucovorin calcium and G-CSF support as in regimen A for courses 1 and 3 and R-IVAC chemotherapy with leucovorin calcium and G-CSF support (as below) for courses 2 and 4. R-IVAC chemotherapy comprises high-dose ifosfamide IV over 3 hours and etoposide IV over 1 hour on days 1-5; cytarabine IV over 3 hours twice daily on days 2 and 3; and rituximab IV over 2-4 hours on day 0 and on day 6 or 7. Patients also receive leucovorin calcium orally every 6 hours on day 6 and G-CSF SC once daily beginning on day 6 or 7 and continuing until blood counts recover. Patients without CNS involvement receive CNS prophylaxis comprising cytarabine IT on days 1 and 3 and MTX IT on day 15 in courses 1 and 3 and MTX IT alone on day 5 in courses 2 and 4. Patients with proven CNS involvement at diagnosis receive cytarabine IT on days 1, 3, and 5 in course 1, on days 7 and 9 in course 2, and on days 1 and 3 in course 3. These patients also receive MTX IT on days 15 and 17 in course 1, on day 5 in courses 2 and 4, and on day 15 in course 3. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.

The first 10 patients enrolled on the study undergo cerebrospinal fluid and blood collection during courses 1 and 3 for correlative biological marker and pharmacological studies.

After completion of study treatment, patients are followed at 30 days and then periodically for up to 3 years.

PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.