Ofatumumab Bendamustine Combination Compared With Bendamustine Monotherapy in Indolent B-cell NHL Unresponsive to Rituxtherapy
Condition: Lymphoma, Follicular
MeSH terms: Lymphoma; Lymphoma, Follicular
Intervention: Ofatumumab; Bendamustine infusion; Ofatumumab and Bendamustine infusions (Arm A); Bendamustine infusion (Arm B)
Intervention description: Ofatumumab was a liquid concentrate solution for infusion presented in glass vials containing 50 mL of solution at a concentration of 20 mg/mL to provide 1000 mg per vial. The ofatumumab infusions were prepared in 1000 mL sterile, pyrogen-free 0.9% NaCl to yield a 1 mg/mL ofatumumab concentration infusion.; Bendamustine 100 mg/vial, injection; Up to 8 cycles of Bendamustine (90 mg/m2 Days 1 and 2, every 21 days) given in combination with 12 doses of ofatumumab (1000 mg). Ofatumumab will be given on day 1 of each cycle of bendamustine as long as patients in Arm A receive bendamustine. Once patients in Arm A complete bendamustine therapy, the remaining doses of ofatumumab will be given monthly until all 12 doses are completed.; Bendamustine (120 mg/m2 Days 1 and 2, every 21 days, up to 8 cycles).
Intervention MeSH terms: Bendamustine Hydrochloride; Ofatumumab; Antibodies, Monoclonal
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: randomized open label bendamustine monotherapy vs. ofatumumab
Masking: None (Open Label)
Enrollment: 346.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Refractory; Safety; Efficacy; Rituximab refractory; Oncology; Ofatumumab; Bendamustine; Indolent B-cell Non- Hodgkin's Lymphoma Unresponsive; Rituximab; Rituximab-Containing Regimen

Summary:

      The purpose of this study was to evaluate the safety and efficacy of ofatumumab and
      bendamustine combination therapy in patients with indolent B-cell NHL that did not respond to
      rituximab or a rituximab-containing regimen during or within 6 months of the last rituximab
      treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Indolent lymphoma including Grades 1-3a follicular, small lymphocytic,
             lymphoplasmacytic, and marginal zone lymphoma; Stages III-IV, or bulky disease, Stage
             II. Tumor verified CD20+ and CT imaging done at screening verifying disease

          -  Indolent B-cell NHL that remains stable or unresponsive during or within 6 months of
             treatment with rituximab or a rituximab-containing regimen

          -  Indolent lymphoma including grades 1-3a follicular, small lymphocytic,
             lymphoplasmacytic, and marginal zone lymphoma; stages III-IV, or bulky disease stage
             II (i.e. as any single mass > 5 cm in any direction)

          -  ECOG Performance Status of 0, 1, or 2

          -  Life expectancy of at least 6 months

          -  18 years or older

          -  Signed, written informed consent

        Exclusion Criteria:

          -  Grade 3b follicular lymphoma or evidence that the indolent lymphoma has transformed to
             aggressive lymphoma

          -  Previous allogeneic stem cell transplant

          -  Previous autologous stem cell transplant, fludarabine therapy, or radioimmunotherapy
             in the past 12 months

          -  Previous external beam radiation therapy to the pelvis. Previous external beam
             radiation therapy for bony disease to the cranium, mediastinum, and axilla, or to two
             or to more than 3 vertebral bodies

          -  High dose steroids greater to or equal to 60 mg prednisone/day (or equivalent) within
             3 months of randomization. No more than 10 mg prednisone (or equivalent) daily at the
             time of randomization

          -  Prior bendamustine treatment within 1 year of randomization not resulting in a CR or
             PR for at least 6 months

          -  Treatment with anti-CD20 monoclonal antibody within 3 months of randomization

          -  Known CNS involvement of indolent lymphoma

          -  Other past or current malignancy. Subjects free of malignancy for at least 5 years or
             have history of definitively treated non-melanoma skin cancer, or successfully treated
             in situ carcinoma, are eligible

          -  Chronic or current active infectious disease requiring systemic antibiotics,
             antifungal, or antiviral treatment

          -  Clinically significant cardiac disease

          -  History of significant cerebrovascular disease or event with significant symptoms

          -  Positive serology for Hepatitis B

          -  Current active liver or biliary disease (except Gibber's syndrome or asymptomatic
             gallstones, liver metastases, or otherwise stable chronic liver disease)

          -  Known HIV positive

          -  Abnormal/inadequate blood values, liver and kidney function

          -  Current participation in other clinical study

          -  Inability to comply with the protocol activities

          -  Lactating or pregnant women or female patients of child-bearing potential (or male
             patients with such partners) not willing to use adequate contraception