Trial Information

A Clinico-Pathologic Study of Primary Mediastinal B-Cell Lymphoma (IELSG 26)

OBJECTIVES:

Primary

- To systematically analyze the phenotype and molecular characteristics in patients with
primary mediastinal diffuse large B-cell lymphoma.

- To determine the PET response rate following chemoimmunotherapy in these patients.

Secondary

- To obtain data, on a nonrandomized basis, regarding the outcomes of treatment using
different chemoimmunotherapy regimens and using or omitting mediastinal radiotherapy,
depending upon the practice of the participating institutions.

- To analyze progression-free and overall survival in patients treated with these
regimens.

OUTLINE: This is a multicenter study.

Patients receive any one of the following standard chemoimmunotherapy regimens.

- Cohort 1 (R-CHOP-21): Patients receive rituximab IV, cyclophosphamide IV, doxorubicin
hydrochloride IV, and vincristine IV on day 1 and oral prednisolone on days 1-5.
Treatment repeats every 21 days in the absence of disease progression or unacceptable
toxicity.

- Cohort 2 (R-CHOP-14): Patients receive rituximab IV, cyclophosphamide IV, doxorubicin
hydrochloride IV, and vincristine IV on day 1, oral prednisolone on days 1-5, and
filgrastim (G-CSF) subcutaneously (SC) on days 5-12. Treatment repeats every 14 days in
the absence of disease progression or unacceptable toxicity.

- Cohort 3 (R-MACOP-B): Patients receive rituximab IV on days 1, 22, 43, 64, 85, and 106;
cyclophosphamide IV and doxorubicin hydrochloride IV on days 1, 15, 29, 43, 57, and 71;
methotrexate IV on days 8, 36, and 64; vincristine IV on days 8, 22, 36, 50 ,64, and
78; bleomycin IV on days 22, 50, and 78; and oral prednisolone on days 1-84, followed
by a taper.

- Cohort 4 (R-VACOP-B): Patients receive rituximab IV on days 1, 22, 43, 64, 85, and 106;
cyclophosphamide IV on days 1, 29, and 57; doxorubicin hydrochloride IV on days 1, 15,
29, 43, 57, and 71; etoposide phosphate IV on days 15, 16, 43, 44, 71, and 72;
vincristine IV and bleomycin IV on days 8, 22, 36, 50, 64, and 78; and oral
prednisolone on days 1-84, followed by a taper.

- Cohort 5 (R-ACVBP): Patients receive rituximab IV, doxorubicin hydrochloride IV, and
cyclophosphamide IV on day 1; vindesine IV and bleomycin IV on days 1 and 5; oral
prednisone on days 1-5; methotrexate intrathecally on day 2; and G-CSF SC on days 6-13
for 4 courses in the absence of disease progression or unacceptable toxicity. After
completion of 4 courses of R-ACVBP, patients receive consolidation therapy comprising
high-dose methotrexate IV, rituximab IV, ifosfamide IV, etoposide phosphate IV, and
cytarabine SC according to protocol GELA LNH03-2B.

Patients with an International Prognostic Index score of 4 or greater or disease in close
proximity to the spinal cord or cerebral meninges may receive prophylactic treatment to the
CNS according to local protocol.

Beginning 8 weeks after completion of chemoimmunotherapy, patients undergo radiotherapy to
the original tumor volume according to local protocol.

Fresh or fixed tissue from prior biopsy is obtained if possible. Samples are analyzed for
CD3, CD20, CD30, CD15, CD10, Bcl-6, Bcl-2, MAL protein (if available), and Ki-67 via
immunohistochemistry.

After completion of study treatment, patients are followed periodically.