OFOCIR: This phase II trial is assessing two oral drugs and one intravenous drug in previously untreated elderly patients with Chronic Lymphocytic Leukaemia (CLL)An Australasian, phase II, multicentre, randomised, dose intensification study investigating oral fludarabine, oral cyclophosphamide and i.v. rituximab (poFCivR) tolerance in previously untreated elderly (= 65 years old) patients with chronic lymphocytic leukaemia (CLL) (Other IDs: ALLG CLL5).

Exclusion

1. Age < 65 years old.
2. Non-progressive or stable Binet stage A.
3. Clinically significant auto-immune cytopenia, Coombs-positive haemolytic anaemia (as
discerned by treating physician).
4. Active second malignancy currently requiring treatment (except for non-melanoma skin
cancer or cervical cancer in situ or tumour treated curatively by surgery > 5 years ago)
5. Concomitant disease requiring prolonged use of glucocorticoids (> 1 month).
6. Known hypersensitivity with anaphylactic reaction to humanised monoclonal antibodies or
any of the study drugs.
7. ECOG performance status 2-3.
8. Class III or IV cardiac disease defined by the NYHA.
9. Severe or debilitating pulmonary disease.
10. Severe or debilitating central nervous system disease or cerebral dysfunction.
11. Transformation to aggressive B-cell malignancy, e.g. diffuse large cell lymphoma, Richter’s
syndrome or prolymphocytic leukaemia.
12. Active bacterial, viral or fungal infection; patients who have known Human Immunodeficiency
Virus (HIV) infection or active hepatitis B virus (HBV) or hepatitis C virus
(HCV) infection.
13. Total bilirubin > 2 x ULN.
14. Creatinine clearance < 50 ml/min (as calculated by eGFR).
15. Any coexisting medical or psychological condition that would preclude participation in the
required study procedures.
16. Treatment with any other investigational agent, or participation in another clinical trial
within 30 days prior to entering this study.
17. Pregnancy and lactation.