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

Phase II Study to Establish Gene Expression Models Predicting Survival of Diffuse Large B-Cell Lymphoma Patients Treated With R-CHOP

The investigators hypothesize that survival of newly diagnosed DLBCL (diffuse large B-cell lymphoma) patients treated with R-CHOP can be predicted by RNA or protein gene expression or by presence of biomarkers associated with the anti-tumor effects of Rituximab.

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.