RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride liposome, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving rituximab together with combination chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving doxorubicin hydrochloride liposome and rituximab together with combination chemotherapy works in treating patients with newly diagnosed Burkitt's lymphoma or Burkitt-like lymphoma.

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.

DISEASE CHARACTERISTICS:

• Histologically confirmed Burkitt's or Burkitt-like non-Hodgkin's lymphoma meeting 1 of the following risk criteria:

  • Low-risk disease meeting all of the following criteria:

    • Normal lactate dehydrogenase level
    • ECOG performance status 0-1
    • Ann Arbor stage I or II
    • No tumor mass over 10 cm in greatest diameter

  • High-risk disease, defined as disease not meeting low-risk criteria

• Newly diagnosed disease

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Hemoglobin ≥ 8.0 g/dL

• Absolute neutrophil count ≥ 500/mm³

• Platelet count ≥ 100,000/mm³ (50,000/mm³ if bone marrow involvement is documented)

• AST and ALT ≤ 3 times upper limit of normal (ULN)

• Alkaline phosphatase ≤ 3 times ULN

• Bilirubin ≤ 1.5 times ULN (3 times ULN if liver metastases are present)

• Creatinine clearance > 50 mL/min

• Creatinine ≤ 2.0 mg/dL

• LVEF ≥ 45% by MUGA scan or echocardiogram

• No New York Heart Association class II-IV heart failure

• No clinically significant pericardial disease

• No myocardial infarction within the past 6 months

• No uncontrolled angina

• No severe uncontrolled ventricular arrhythmias

• No ECG evidence of acute ischemia or active conduction system abnormalities

  • Investigator must document any baseline ECG abnormality as not medically relevant

• No other malignancy within the past year except for basal cell carcinoma of the skin or in situ carcinoma of the cervix

• No other serious medical or psychiatric illness that would preclude study compliance

PRIOR CONCURRENT THERAPY:

• Prior treatment with 1 course of any combination of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and/or prednisone* (CHOP)-like therapy allowed, provided the following doses are not exceeded:

  • Rituximab 750 mg/m²
  • Cyclophosphamide 1,000 mg/m²
  • Doxorubicin hydrochloride 50 mg/m²
  • Vincristine 2 mg/m²

• No other investigational drugs within the past 14 days

• No other concurrent systemic, cytotoxic, investigational, or chemotherapy agents NOTE: *No maximum dose restriction on steroids