Study of Bendamustine and Ofatumumab in Elderly Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma Who Are Poor Candidates for R-CHOP Chemotherapy
Condition: Diffuse Large B-Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
Intervention: Bendamustine; Ofatumumab
Intervention description: Patients will receive as an IV infusion bendamustine 90 mg/m^2 Days 1 and 2 of Cycles 1 through 6.; Patients will receive as an IV infusion ofatumumab 1000-mg IV Days 1 and 8 during Cycle 1 only, and on Day 1 of Cycles 2 through 6
Intervention MeSH terms: Bendamustine Hydrochloride; Ofatumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 70 Years
Healthy volunteers: No
Keywords: Diffuse Large B-Cell Lymphoma; Ofatumumab; Bendamustine

Summary:

      This is a single-arm, Phase II study designed to enroll and treat up to 64 patients. All
      patients in this study will receive ofatumumab and bendamustine as an IV infusion for 6
      cycles (a cycle is defined as 21 days in length). Patients will receive as an IV infusion
      bendamustine Days 1 and 2 of Cycles 1 through 6 and ofatumumab Days 1 and 8 during Cycle 1
      only and on Day 1 of Cycles 2 through 6.
    

Eligibility criteria:

        Inclusion Criteria:

          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
                  anthracycline therapy.

               -  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)

        Exclusion Criteria:

          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 >=
             1 year.

         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
             Investigator.

         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
             the patient.

         16. Male patients unable or unwilling to use adequate contraception methods from study
             start to one year after the last dose of protocol therapy.