Inclusion criteria

1. CLL requiring treatment by NCI/IWCLL 2008 criteria. At least one of the following criteria:
   1. Progressive marrow failure as manifested by the development of, or worsening of, anaemia and/or thrombocytopenia.
   2.  Massive (i.e. 6 cm below the left costal margin) or progressive or symptomatic splenomegaly.
   3. Massive (i.e. 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy.
   4. Progressive lymphocytosis with an increase of more than 50% over a 2-month period or lymphocyte doubling time (LDT) of less than 6 months.
2. No prior therapy for CLL
3. Full-dose R-FC considered inappropriate for at least one of the following reasons
   1. Age 75 or greater
   2. WHO performance status 2 or 3
   3. Cardiac impairment (NYHA class II)
   4. Respiratory impairment (bronchiectasis or moderate COPD)
   5. Renal impairment (estimated Glomerular Filtration Rate (eGFR) 10-30 ml/min)
   6. Any other significant co-morbidity or factor that makes R-FC inappropriate
4. Considered able to tolerate Chl at the dose used in the LRF CLL4 trial (10mg/m2 d1-7)
5. Written informed consent

Exclusion criteria

1. Neutrophil count less than 1.0 x 109/l or platelet count less than 50 x 109/l unless due to CLL*
2. Uncontrolled auto-immune haemolytic anaemia or thrombocytopenia
3. Active infection
4. Seropositivity for HIV, HCV or HBV (surface antigen or core antibody)
5. Severe renal impairment (eGFR less than 10ml/min)
6. Severe hepatic impairment (serum bilirubin more than twice the upper limit of normal) unless due to CLL or Gilbert’s syndrome.
7. Concurrent treatment with glucocorticoids equivalent to more than prednisolone 20mg od
8. Prior treatment with monoclonal antibody therapy within the last 3 months.
9. Yellow fever vaccination within 4 weeks prior to treatment start
10. Known hypersensitivity to ofatumumab, bendamustine or chlorambucil or any of their excipients
11. CNS involvement with CLL
12. History of Richter transformation
13. Concomitant malignancies within the last 3 years except successfully treated non-melanoma skin cancer or carcinoma in situ.
14. Major surgery within 28 days prior to randomisation
15. WHO performance status 4
16. Severe cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (NYHA III-IV), and arrhythmia (excluding extra systoles or minor conduction abnormalities) unless controlled by therapy.
17. Any serious underlying medical or psychological conditions, which could impair the ability of the patient to participate in the trial or compromise ability to give informed consent
18. Treatment within a clinical trial within 30 days prior to trial entry.
19. Adult patient under tutelage (not competent to sign informed consent).
20. Pregnant or lactating women.