Inclusion Criteria:

- Newly diagnosed patients with Diffuse Large B-cell Lymphoma (DLBCL) (any stage) OR
composite lymphoma with >= 50% DLBCL

- Adequate diagnostic tissue for microarray gene expression analysis or IHC analysis

- Karnofsky Performance Status >= 70 (ECOG 0, 1)

- No prior chemotherapy (with the exception of 1 cycle CHOP-R based on current
diagnosis, clinical condition, and availability/feasibility of initiating Genasense),
immunotherapy, radiotherapy, or investigational therapies for NHL; steroid therapy is
allowed only if required for maintenance of another chronic disease (e.g., rheumatoid
arthritis)

- Patients aged >= 60 years, or patients with a history of coronary artery disease,
congestive heart failure, hypertension, diabetes, or hyperlipidemia must have an
estimated ejection fraction >= 0.45 (45%) by MUGA or echocardiography, performed
within two months of study entry

- Patients must be willing to give written informed consent, and sign an
institutionally approved consent form prior to initiating genasense or any study
related activities (i.e., Genasense & microarray)

- Females of childbearing potential must have a negative serum pregnancy test prior to
enrollment in the study

- Adequate venous access for 7-day continuous infusion

- Patients without evidence of severe organ dysfunction as determined within two weeks
of 1st cycle of CHOP-R: 1) Hemoglobin > 8 g/dl; 2) Absolute neutrophil count > 1000/;
3) Platelets > 100,000 (lower blood counts may be acceptable if due to lymphoma after
review with principal investigator); 4) Creatinine =< 2.0 mg/dL (unless due to NHL);
5) Bilirubin =< 2.0 mg/dL; 6) AST =< 3 x upper normal; 7) ALP =< 3 x upper normal
(unless due to NHL)

- Men and women of reproductive potential must agree to use TWO of the following forms
of birth control every time they have sex throughout the study and for up to 3 months
following discontinuation of study drug: hormonal birth control methods, condoms
(male or female) with or without a spermicidal agent, diaphragm or cervical cap with
spermicidal, IUD, or surgical sterilization while participating in this study

Exclusion Criteria:

- Significant medical disease other than cancer including: 1) Any bleeding or
coagulation disorder including a history of autoimmune hemolytic anemia or autoimmune
thrombocytopenia; 2) Severe pulmonary disease; 3) Uncontrolled congestive heart
failure; 4) New York Heart Association class III or IV disease; 5) Uncontrolled
seizure disorder; and 6) Active infections

- Less than 3 weeks from prior major surgery

- Prior organ allograft

- Known HIV infection (due to expected frequent occurrence of myelo-suppression and
immunosuppression)

- Women who are pregnant (confirmed by a serum pregnancy test in females of
reproductive potential) or breast-feeding (women of child-bearing potential and
sexually active males must be advised to take precautions to prevent pregnancy during
treatment or remain abstinent)

- Women of child-bearing potential and sexually active males must be advised to take
precautions to prevent pregnancy during treatment (unless the subject or subject's
partner(s) is sterile, i.e., women who have had a hysterectomy or have been
post-menopausal for at least twelve consecutive months) or remain abstinent

- Known hypersensitivity to phosphorothiate-containing oligonucleotides

- Concurrent investigational, corticosteroid therapy or any other anti-cancer
treatments (such as chemotherapy, radiation, biologic or investigational therapies)
while receiving protocol therapy; other than one cycle CHOP-R allowed based on
current diagnosis, clinical condition, and availability/feasibility of initiating
Genasense; other than chronic steroid use for another indication (For stage I/II or
as clinically indicated- involved field irradiation as per standard practice is
accepted)

- Other investigational drug therapy within 30 days of study entry

- Secondary leukemia or history of antecedent hematologic disorder

- History of second cancer (except for adequately treated basal cell or squamous cell
skin cancer, in situ cervical cancer, or other cancer for which the patient has been
disease-free for three or more years)

- No active CNS disease defined as symptomatic meningeal lymphoma or known CNS
parenchymal lymphoma

- Concomitant anticoagulant therapy is not permitted (with the exception of 1 mg/day of
warfarin for central line prophylaxis)

- Known hypersensitivity to G3139 (Genasense) or R-CHOP

- Neurologic disorders, overt psychosis, mental disability or evidence of limited
capacity to provide fully informed consent or cooperation with the complexities of
the treatment program