Rituximab Plus CHOP With Sargramostim in Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma

Inclusion Criteria:

1. Previously untreated, histologically or cytologically documented diffuse large B cell
non-Hodgkin's lymphoma.

2. Lymphoma must be CD20 positive.

3. All stages of disease.

4. Measurable or non-measurable tumor parameter(s). Non-measurable tumor parameters will
be defined as not having bi-dimensional measurements (i.e. gastric or marrow
involvement) but can be followed for response by other diagnostic tests such as
gallium, PET imaging and/or bone marrow biopsy.

5. Age ≥ 18 years.

6. KPS ≥ 50% (ECOG PS 0, 1, or 2).

7. Able to give signed informed consent.

8. Adequate hepatic function: bilirubin ≤ 2.0 mg/dl (unless elevated secondary to
lymphomatous involvement of liver or biliary system. For bilirubin > 3.0 due to
hepatic involvement, the initial dose of doxorubicin will be decreased by 50%, and the
initial dose of vincristine will be omitted. SGOT <5X upper limit of normal.

9. Adequate renal function: creatinine < 2.0 mg/dl, or creatinine clearance ≥ 60 ml/min,
unless secondary to renal involvement by lymphoma.

10. Adequate hematologic function: granulocytes (ANC) >1000/mm3, platelets > 75,000/dl,
unless these parameters are abnormal secondary to lymphomatous involvement of bone
marrow. All patients must be off colony stimulating factor therapy at least 24 hours
prior to institution of cycle #1 chemotherapy.

11. Left ventricular ejection fraction that is at or above the lower institutional limits
of normal, as assessed by nuclear scan or echocardiogram obtained within 6 weeks of
registration.

12. Concurrent radiation with or without steroids for emergency conditions secondary to
lymphoma (i.e. CNS tumor, cord compression, etc) will be permitted, provided that
additional, measurable or evaluable sites of lymphomatous disease are present at study
entry.

13. Female patients must have a negative pregnancy test within 72 hours of entering into
the study. Both men and women will be included and, if of child bearing potential,
must agree to use adequate contraception for the duration of the treatment. Women must
avoid pregnancy and men avoid fathering children while in the study.

Exclusion Criteria:

1. Presence of second active tumor, other than non melanomatous skin cancer, carcinoma in
situ of the cervix.

2. Primary central nervous system lymphoma, including parenchymal brain or spinal cord
lymphoma.

3. Pregnant women or nursing mothers.

4. ECOG performance score 3 or more (KPS <50%).

5. Expected survival < 3 months.

6. Unable to comply with the requirements of the protocol, or unable to provide adequate
informed consent in the opinion of the principal investigator.

7. Serious, on-going non-malignant disease or infection, which, in the opinion of the
investigator and/or the sponsor, would compromise other protocol objectives.

8. Major surgery, other than diagnostic surgery, within four weeks.

9. History of prior therapy with Rituximab within 12 months. Patients treated with
Rituximab more than 12 months earlier are eligible only if it was given for
indications other than the treatment of aggressive lymphoma.

10. History of prior cytotoxic chemotherapy or radiotherapy for this lymphoma.

11. History of cutaneous or muco-cutaneous reactions or diseases in the past, due to any
cause, severe enough to cause hospitalization or an inability to eat or drink for 2
days or more. This exclusion relates to the long-term possibility of severe
muco-cutaneous or cutaneous reactions to Rituximab, which maybe occurred at increased
frequency in patients who have had severe skin disease or reactions in the past.

12. Any acute inter-current infection that may interfere with planned protocol treatment.