Doxorubicin Hydrochloride Liposome and Rituximab With Combination Chemotherapy 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