This open-label, randomized, 3-arm study will evaluate the efficacy and safety of RO5072759 in combination with chlorambucil as compared to rituximab plus chlorambucil or chlorambucil alone in patients with previously untreated chronic lymphocytic leukemia. Patients will be randomized to receive a maximum of 6 cycles of either RO5072759 (1000mg iv infusion, on days 1, 8 and 15 of cycle 1 and day 1 of cycles 2-6) plus chlorambucil (0.5mg/kg orally, days 1 and 15 of cycles 1-6), or rituximab (iv infusion day 1, 375mg/m2 cycle 1, 500mg/m2 cycles 2-6) plus chlorambucil, or chlorambucil alone. Anticipated time on study treatment is >6 months and follow-up for disease-progression and safety will be at least 5 years. Target sample size is <800. In the US, this trial is sponsored/managed by Genentech.

• Drug: RO5072759
  1000 mg by iv infusion, on days 1,8 and 15 in cycle 1, day 1 in cycles 2-6
• Drug: rituximab
  by iv infusion on day 1 of each cycle, 375 mg/m2 cycle 1, 500 mg/m2 cycles 2-6
• Drug: chlorambucil
  0,5 mg/kg orally on day 1 and 15 of each cycle

• A (GClb): Experimental
  Interventions:

  • Drug: RO5072759
  • Drug: chlorambucil
• B (RClb): Active Comparator
  Interventions:

  • Drug: rituximab
  • Drug: chlorambucil
• C (Clb): Active Comparator
  Intervention: Drug: chlorambucil

Inclusion Criteria:

• adults >/=18 years
• documented CD20+B-CLL
• previously untreated CLL requiring treatment according to the NCI criteria

Exclusion Criteria:

• prior CLL therapy
• transformation of CLL to aggressive NHL (Richter's transformation)
• history of other malignancy unless the malignancy has been in remission without treatment for >/=2 years prior to enrolment