Genes in Predicting Outcome of Patients With DLBCL Treated With Rituximab and Combination Chemotherapy (R-CHOP)

In this phase II multi-institutional trial, the investigators will identify genes associated
with either good or bad outcome in DLBCL patients treated with R-CHOP, will construct a
robust predictive models based on RNA extracted from or paraffin specimens as well on
immunohistochemistry and will examine the predictive power of new biomarkers associated with
the anti-tumor effects of rituximab. The acquisition of fixed tissue as a component of this
uniformly treated prospective study will also afford future studies with this informative
dataset.

Inclusion Criteria:

- 1. Diagnosis of diffuse large B-cell lymphoma, CD20-positive, according to the World
Health Organization Classification, stages II-IV or limited stage I disease that is
bulky (more than 10 cm) or with International Prognostic Index (IPI) score > 1.

- 2. Patients must not have had prior chemotherapy, radiotherapy or immunotherapy. A
short course (< 2 weeks) of corticosteroids is allowed.

- 3. Adequate paraffin-embedded tumor specimen must be available for gene expression
analysis and immunohistochemistry prior to initiation of therapy. (If the specimen is
deemed inadequate, the subject can be retroactively screen failed, as this does not
change the treatment regimen).

- 4. Baseline measurements and evaluation must be obtained within 4 weeks before first
treatment.

- 5. Age >18 years.

- 6. Eastern Cooperative Oncology Group (ECOG) performance status 0-3.

- 7. Adequate organ function:

- White Blood Cells count (WBC) >2500/µL

- Absolute Neutrophil Count (ANC) > 1000/µL (unless due to disease in marrow)

- platelet count >100,000/µL (unless due to disease in marrow)

- creatinine < 2.0 mg/dL,

- bilirubin < 1.5 mg/dL (may be 1.5-3.0 mg/dl if due to liver involvement by
lymphoma)

- Serum Glutamic Oxaloacetic Transaminase (SGOT)/ Serum Glutamic Pyruvic
Transaminase (SGPT) <3 x upper limit of normal.

- 8. Female patients must not be pregnant or breast feeding.

- 9. Women of childbearing potential and men must be strongly advised to use an
accepted and effective method of contraception.

- 10. Patients must have left ventricular ejection fraction of >45%.

- 11. Provision of written informed consent.

Exclusion Criteria:

- 1. Patients with a second malignancy other than basal cell carcinoma of the skin or
in situ carcinoma of the cervix unless the tumor was treated with curative intent at
least two years previously; and; the patient continue to be free of evidence of
recurrence.

- 2. Patients with HIV infection as these patients are managed on dedicated protocols.

- 3. Patients with active central nervous system (CNS) lymphoma.