A Phase 3 Study of Ibrutinib (PCI-32765) Versus Ofatumumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia
Condition: Relapsed or Refractory Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma
MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: ofatumumab; ibrutinib
Intervention description: The ofatumumab (IV) dosage and schedule is 12 doses administered over 24 weeks or until disease progression, unacceptable toxicity.
Week 1: 300 mg initial dose Week 2 through 8: 2,000 mg (once weekly) Week 12, 16, 20 and 24: 2,000 mg (every 4 weeks); ibrutinib 420 mg (3 x 140-mg capsules) will be administered orally once daily until disease progression or unacceptable toxicity
Intervention MeSH terms: Ofatumumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 391.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Chronic; SLL; CLL; Ofatumumab; ibrutinib; RESONATE; Phase III; Leukemia; Lymphoma

Summary:

      The purpose of the study is to evaluate whether treatment with ibrutinib as a monotherapy
      results in a clinically significant improvement in progression free survival (PFS) as
      compared to treatment with ofatumumab in patients with relapsed or refractory Chronic
      Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
    

Eligibility criteria:

        Inclusion Criteria:

          -  ECOG performance status of 0-1.

          -  Diagnosis of CLL or SLL that meets IWCLL 2008 criteria.

          -  Active disease meeting at least 1 of the IWCLL 2008 criteria for requiring treatment.

          -  Must have received at least one prior therapy for CLL/SLL.

          -  Considered not appropriate for treatment or retreatment with purine analog based
             therapy.

          -  Measurable nodal disease by CT.

          -  Patients must be able to receive outpatient treatment and laboratory monitoring at the
             institution that administers study drug for the entire study.

        Exclusion Criteria:

          -  Known CNS lymphoma or leukemia.

          -  No documentation of cytogenetic and/or FISH in patient records prior to first dose of
             study drug.

          -  Any history of Richter's transformation or prolymphocytic leukemia.

          -  Uncontrolled Autoimmune Hemolytic Anemia (AIHA) or idiopathic thrombocytopenia purpura
             (ITP).

          -  Prior exposure to ofatumumab or to ibrutinib.

          -  Prior autologous transplant within 6 months prior to first dose of study drug.

          -  Prior allogeneic stem cell transplant within 6 months or with any evidence of active
             graft versus host disease or requirement for immunosuppressants within 28 days prior
             to first dose of study drug.

          -  History of prior malignancy, with the exception of certain skin cancers and
             malignancies treated with curative intent and with no evidence of active disease for
             more than 3 years.

          -  Serologic status reflecting active hepatitis B or C infection.

          -  Unable to swallow capsules or disease significantly affecting gastrointestinal
             function.

          -  Uncontrolled active systemic fungal, bacterial, viral, or other infection.

          -  History of stroke or intracranial hemorrhage within 6 months prior to the first dose
             of study drug.

          -  Requires anticoagulation with warfarin.