Trial Information

A Multicenter Phase II Study Incorporating DOXIL® and Rituximab Into the Magrath Regimen for HIV-Negative and HIV-Positive Patients With Newly Diagnosed Burkitt's and 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.