The purpose of this study is to evaluate the safety and efficacy of ofatumumab added to chlorambucil in patients with untreated Chronic Lymphocytic Leukemia.

Chlorambucil, is currently approved for treatment of frontline chronic lymphocytic leukemia, especially, but not limited to the ailing and elderly patient population. Several other more aggressive treatment options are available (e.g. fludarabine), however they are not suitable for all CLL patients, especially the ailing and elderly, due to greater toxicity. Ofatumumab is effective with low toxicity. The addition of ofatumumab to chlorambucil offers potentially a more effective therapy, with limited toxicity. The objective of this study is to evaluate progression-free survival (PFS), overall response and overall survival in subjects with previously untreated CLL with ofatumumab added to chlorambucil versus chlorambucil.

• Drug: ofatumumab (GSK1841157) infusion
  iv infusion; dose: cycle 1 300mg day 1 and 1000mg day 8, subsequent cycles: 1000mg at day 1 every 28 days;
  Other Names:

  • chlorambucil, tablets
  • ofatumumab (GSK1841157) infusion
• Drug: chlorambucil, tablets
  2mg tablets, chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 cycles

• ofatumumab + chlorambucil: Experimental
  ofatumumab dose: cycle 1 300mg day 1 and 1000mg day 8, subsequent cycles: 1000mg at day 1 every 28 days; chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 treatment cycles
  Interventions:

  • Drug: ofatumumab (GSK1841157) infusion
  • Drug: chlorambucil, tablets
• chlorambucil: Active Comparator
  chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 cycles
  Intervention: Drug: chlorambucil, tablets

Inclusion Criteria:

• confirmed CLL diagnosis and active CLL requiring treatment
• considered inappropriate for fludarabine-based therapy
• not been treated for CLL before
• fully active at a minimum or fully capable of selfcare and up and about more than 50% of waking hours
• age 18yrs or older
• signed written informed consent

Exclusion Criteria:

• prior CLL therapy
• abnormal/inadequate blood values, liver, and kidney function
• certain heart problems, active or chronic infections, serious significant diseases, AIHA, other current cancer or within last 5 years
• CLL transformation
• CLL central nervous system involvement
• 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