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.