Phase II Study of Bendamustine and Ofatumumab in Elderly Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma Who Are Poor Candidates for R-CHOP Chemotherapy
1. Histologically confirmed CD20-positive DLBCL.
2. Newly diagnosed, stage III-IV DLBCL considered poor candidates for R-CHOP.
3. Age >=70 years
4. At least one of the following criteria:
- ECOG PS 2
- Cardiac compromise precluding anthracycline therapy
- Previous anthracycline therapy for other malignancy precluding further
- Severe coexisting medical problems
- General frailty
5. ECOG 0-2
6. Measurable disease with at least one bidimensional lymph node or tumor mass >1.5 cm
in the longest diameter that can be followed for response as a target lesion as
measured by CT
7. Patients must be HBV sAg and HBV cAb negative within 6 weeks of screening.
8. Patient must understand and voluntarily sign the IRB-approved informed consent.
9. Life expectancy >= 3 months
10. Laboratory parameters:
- Absolute neutrophil count >=1,000 cells/mm3
- Platelet count >=75,000 cells/mm3
- Hemoglobin >=8 g/dL
- Creatinine <=2.0 mg/dL or Creatinine Clearance >= 40 mL/min (calculated or 24
hour urine sample)
- AST/SGOT <=2.0 x ULN (<=5.0 x ULN if secondary to lymphoma)
- ALT/SGPT <=2.0 x ULN (<=5.0 x ULN if secondary to lymphoma)
- Bilirubin level of <2.0 mg/dL unless secondary to Gilbert's disease (or pattern
consistent with Gilbert's)
1. Patients with active/symptomatic central nervous system (CNS) involvement based on
clinical evaluation by lumbar puncture, PET, CT or MRI.
2. Known sensitivity to bendamustine or any component of bendamustine.
3. Known anaphylaxis or sensitivity to ofatumumab.
4. Major surgery within 28 days of Cycle 1, Day 1. Patients undergoing minor surgery
within 7 days of Cycle 1, Day 1. (no wait needed for port placement)
5. Prior chemotherapy, immunotherapy, or irradiation for lymphoma.
6. Prior use of investigational anti-cancer agents for lymphoma.
7. HIV-related lymphoma.
8. Known active HIV or HCV infection, or known seropositivity for HIV, or current or
chronic HBV or HCV infection. HBV test required at screening or a negative result
within 6 weeks of screening.
9. Concurrent active or history of other malignancies, except non-melanoma skin cancer
or carcinoma in situ of cervix or breast. Patients with previous malignancies are
eligible provided they have been treated with curative intent and disease free for >=
10. Serious (grade 3-4), active, intercurrent infection requiring therapy, or deep seated
or systemic mycotic infections.
11. Myocardial infarction within 6 months prior to registration or New York Hospital
Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe
uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
ischemia or significant conduction system abnormalities, in the judgment of the
12. Concurrent uncontrolled serious medical or psychiatric conditions likely to interfere
with participation in this clinical study, in the judgment of the Investigator
13. Patients who have current active hepatic or biliary disease (with exception of
patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable
chronic liver disease per investigator assessment).
14. Treatment with any known non-marketed drug substance or experimental therapy within 5
terminal half lives or 4 weeks prior to enrollment, whichever is longer, or currently
participating in any other interventional clinical study.
15. Significant concurrent, uncontrolled medical condition including, but not limited to,
renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or
psychiatric disease which in the opinion of the investigator may represent a risk for
16. Male patients unable or unwilling to use adequate contraception methods from study
start to one year after the last dose of protocol therapy.