A Phase 3 Study of Ibrutinib (PCI-32765) Versus Ofatumumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia (RESONATE™)

• OS (Overall Survival) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
• Hematological Improvements [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
• Improvement of disease-related symptoms (fatigue, night sweats, and splenomegaly). [ Time Frame: 2 years ] [ Designated as safety issue: No ]

• ORR (Overall Response Rate) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• OS (Overall Survival) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
• Hematological Improvements [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
• Investigator-assessed PFS [ Time Frame: Time from randomization until disease progression ] [ Designated as safety issue: No ]
• Investigator-assessed ORR [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Improvement of disease-related symptoms (fatigue, night sweats, and splenomegaly). [ Time Frame: 2 years ] [ Designated as safety issue: No ]

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)

• Relapsed or Refractory Chronic Lymphocytic Leukemia
• Small Lymphocytic Lymphoma

• Drug: ofatumumab

  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)

• Drug: ibrutinib
  ibrutinib 420 mg (3 x 140-mg capsules) will be administered orally once daily until disease progression or unacceptable toxicity

• Active Comparator: Ofatumumab (Arm A)
  An anti-CD20 monoclonal antibody
  Intervention: Drug: ofatumumab
• Experimental: ibrutinib (Arm B)
  A Bruton Tyrosine Kinase Inhibitor
  Intervention: Drug: ibrutinib

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/allogeneic transplant
• 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.