Patients With Relapsed or Refractory Diffuse Large B Cell Non Hodgkin Lymphomas
Condition: Non-Hodgkin Lymphomas
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell
Intervention: Ofatumumab
Intervention description: The first dose administered of ofatumumab should be 300 mg to minimize infusion reactions. The initial rate of the first infusion of 1000 mg ofatumumab (0.3mg/ml) should be 12ml/h. If no infusion reactions occur the infusion rate should be increased every 30 minutes, to a maximum of 400 ml/h. If this schedule is followed, the infusion duration will be approximately 4.5 hours.
Intervention MeSH terms: Ofatumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ofatumumab diffuse B cell non hodgkins lymphoma DLBCL; refractory DLBCL; relapsed DLBCL

Summary:

      This is a phase II open label study that looks at the efficacy and toxicity of Ofatumumab
      monotherapy in patients with relapsed and/or refractory diffuse large B-cell lymphoma
      (DLBCL). Patients will receive weekly infusions of Ofatumumab of 1000 mg each for 8 weeks
      (induction phase) followed by continuing the study drugs every other week in subsequent
      cycles (maintenance phase). Each 4 weeks of therapy will be calculated as one cycle.
      Treatment will continue until disease progression, toxicity, patient's withdrawal, or
      investigator's discretion.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Relapsed and/or refractory DLBCL,not HSCT candidates. Pts must have failed standard of
             care (SOC) therapy w/rituximab plus CHOP or its equivalent & not considered
             hematopoietic stem cell transplant (HSCT) candidates based on investigator's
             discretion

          -  Pts must have measurable disease radiographically on CT and/or PET scans and/or bone
             marrow biopsy.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

          -  Age ≥18 years. No upper limit of age

          -  Life expectancy of 6 months or more based on investigator's best estimate.

          -  Pts able to read, understand, & sign informed consent

          -  Evidence of CD20 positivity in treated pts, using flow or immunohistochemistry.

          -  Pts will be stratified based on bulk of disease (bulk defined as any area w/ more than
             5cm in greatest dimension)

          -  Pts must agree to an acceptable form of birth control

        Exclusion Criteria:

          -  Other histologies of non-Hodgkin's lymphoma (NHL)

          -  Known central nervous system (CNS) involvement with NHL

          -  Known HIV positive status

          -  Chronic or current active infectious disease requiring systemic antibiotics,
             antifungal, or antiviral treatment.

          -  Corticosteroid use is allowed as long as it is for non-lymphoma related causes such as
             rheumatoid arthritis and chronic obstructive pulmonary disease (COPD).

          -  Pts w/prior malignancies are allowed as long as they are in remission & their last
             treatment for such malignancy is 2 years prior to enrollment or more. Pts
             w/non-melanoma skin cancers that have received adequate therapy prior to enrollment &
             women w/history of cervical cancers are allowed.

          -  Significant concurrent uncontrolled medical condition including, but not limited to,
             renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurologic,
             cerebral, or psychiatric disease.

          -  Current active liver or biliary disease (with the exception of Gilbert's syndrome or
             asymptomatic gallstones, liver metastases, or otherwise stable chronic liver disease
             per the investigator's assessment).

          -  Adequate bone marrow function by virtue of having Platelets >50,000/ul & absolute
             neutrophil count (ANC) >1000/ul is required unless low counts are attributed to
             diffuse bone marrow infiltration with NHL as documented with a bone marrow biopsy
             exam.

          -  Pts with creatinine >2.0 times the upper limit of normal will be excluded unless they
             have a normal creatinine clearance-estimated or measure 12 or 24 hour creatinine
             clearance of <60 mL/min

          -  Pts w/total bilirubin >1.5 times upper limit of normal will be excluded, unless due to
             DLBCL involvement of liver or a known history of Gilbert's disease.

          -  Pts with aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/Alkaline
             phosphatase (Alk Phos) >2.5 times upper limit of normal

          -  Previous tx with Ofatumumab

          -  Prior exposure to an investigational agent within 4-weeks from starting Ofatumumab

          -  History of significant cerebrovascular disease or event w/significant symptoms or
             sequelae

          -  Clinically significant cardiac disease including unstable angina, acute myocardial
             infarction within 6 months prior to randomization, congestive heart failure (NYHA
             III-IV), & arrhythmia unless controlled by therapy, w/exception of extra systoles or
             minor conduction abnormalities.

          -  Positive serology for hepatitis B (HB) defined as a positive test for HBsAg. In
             addition, if negative for HBsAg but HBcAb positive & regardless of HBsAb status, a HB
             DNA test will be performed and if positive the subject to be excluded. Note: If HBcAb
             positive and HBsAb positive, which is indicative of a past infection, subject can be
             included

          -  Positive serology for hepatitis C (HC) defined as a positive test for HCAb, in which
             case reflexively perform a HC RIBA immunoblot assay on the same sample to confirm the
             result.

          -  Pregnant or lactating women. Women of childbearing potential must have a negative
             pregnancy test at screening, including women whose last menstrual period was less than
             1 year prior to screening, unable or unwilling to use adequate contraception from
             study start to 1 year after the last dose of protocol therapy. Adequate contraception
             is defined as hormonal birth control, intrauterine device, double barrier method or
             total abstinence.