Biological Therapy and Combination Chemotherapy in Treating Patients With Lymphomatoid Granulomatosis

OBJECTIVES:

- Determine the long-term efficacy of interferon alfa in patients with lymphomatoid
granulomatosis.

- Determine the long-term efficacy of etoposide, prednisone, vincristine,
cyclophosphamide, doxorubicin, and rituximab in patients with grade III lymphomatoid
granulomatosis OR in patients who fail interferon therapy.

- Determine the response in patients treated with these regimens.

OUTLINE: Patients are stratified according to disease status (grade I or II lymphomatoid
granulomatosis [LYG] vs grade III LYG).

Regimen A (grade I or II LYG):

- Patients receive interferon alfa (IFN-A) subcutaneously (SC) 3 times a week for at
least 1-3 years. Patients with complete remission or stable disease receive IFN-A for
an additional 12 months. Patients with progressive disease proceed to chemotherapy on
regimen B.

Regimen B (grade III LYG OR disease progression on IFN-A):

- Patients receive rituximab IV on day 1; doxorubicin IV, etoposide IV, and vincristine
IV continuously on days 1-4; cyclophosphamide IV on day 5; and oral prednisone twice a
day on days 1-5. Patients receive filgrastim (G-CSF) SC beginning on day 6 and
continuing until blood counts recover. Treatment repeats every 21 days for 6-8 courses.

Patients who achieve a partial remission on chemotherapy receive IFN-A as in regimen A
beginning 4 weeks after completion of chemotherapy.

Patients receiving treatment on regimen A with evidence of disease progression or aggressive
lymphoma in the CNS who are experiencing neurological symptoms warranting treatment OR
receiving treatment on regimen B may be treated with intrathecal methotrexate or cytarabine
and/or craniospinal radiotherapy. Patients with progressive disease after intrathecal
chemotherapy may receive radiotherapy. Patients with parenchymal involvement of the brain
receive standard whole brain radiotherapy.

Patients with progressive disease on chemotherapy and/or IFN-A may receive standard
treatment including rituximab.

Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months
for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study.