Bendamustine + Rituximab in Older Patients With Previously Untreated Diffuse Large B-cell Lymphoma

This multicenter Phase II clinical study will investigate the complete response (CR) rate
after therapy with bendamustine combined with rituximab in older (≥65 years old) patients
with previously untreated stage II-IV DLBCL deemed poor candidates for cyclophosphamide,
doxorubicin hydrochloride, vincristine (Oncovin®), prednisone, rituximab (CHOP-R); n=37. The
hypothesis being tested is that this regimen will be safe and effective as frontline therapy
in older DLBCL patients deemed poor candidates for CHOP-R. After 3 cycles of therapy,
patients with less than a partial response (PR) will come off study, and be managed at the
discretion of their treating physician. Patients who achieve a PR after 3 cycles will
continue for a total of 8 cycles of therapy, while patients who achieve a CR will continue
for a total of 6 cycles of therapy. Secondary objectives include overall response rates
(ORR), disease-free, progression-free and overall survival, and an evaluation of the
toxicity and tolerability of the regimen.

This trial also includes an exploratory analysis designed to evaluate a potential
correlation between expression of the senescence marker p16INK4a and the toxicity associated
with this regimen.

In addition, patients will be asked to participate in a Geriatric Assessment (GA) tool
during the trial.

Inclusion Criteria:

- Patients with previously untreated , histologically confirmed, diffuse large B-cell
lymphoma (DLBCL), immunophenotyped for CD20

- Age greater than or equal to 65 years

- Stage II-IV

- Measurable disease including lesions that can be accurately measured in 2 dimensions
by CT and have a greatest transverse diameter of 1cm or greater, and/or by bone
marrow histopathology.

- ECOG performance status of 0-3

- Deemed poor candidate for CHOP-R due to ejection fraction less than or equal to 45%,
ECOG performance status of 2, or in the opinion of the treating physician, patient
would not tolerate administration of CHOP-R chemotherapy for other reasons,

- Life expectancy of at least 3 months;

- Documented negative serologic testing for HIV, Hepatitis B (unless positive due to
prior vaccination), and hepatitis C within the year prior to enrollment

- Adequate bone marrow function (without transfusion support within one week of
screening) function:

- Hemoglobin > 8 g/dL

- Absolute neutrophil count (ANC) >1000 cells/mm3

- Platelet count > 75,000/mm3

- Adequate hepatic and renal function as demonstrated by:

- Aspartate aminotransferase (AST) < 2.5 x upper limit of normal (ULN)

- Total serum bilirubin < 2.5 x ULN

- Serum creatinine < 1.5 x ULN

- If sexually active male of reproductive capability, has agreed to use a medically
accepted form of contraception from time of enrollment to completion of all follow-up
study visits

- Signed an institutional review board (IRB) approved informed consent document

Exclusion Criteria:

- Central nervous system involvement by lymphoma

- History of previous allergic reactions to compounds of similar biological or chemical
composition as rituximab or bendamustine

- Medical or other condition that would represent an inappropriate risk to the patient
or would likely compromise achievement of the primary study objective.

- Other active malignancies (except: non-melanoma skin cancer, cervical carcinoma in
situ without evidence of disease, prostatic intraepithelial neoplasia without
evidence of prostate cancer)

- Patients on strong inhibitors of CYP1A2.