Lumiliximab With Fludarabine, Cyclophosphamide, and Rituximab (FCR) Versus FCR Alone in Subjects With Relapsed Chronic Lymphocytic Leukemia (CLL)
Lumiliximab With Fludarabine, Cyclophosphamide, and Rituximab (FCR) Versus FCR Alone in Subjects With Relapsed Chronic Lymphocytic Leukemia (CLL)
This is a randomized (1:1), open-label, multicenter, active-controlled study in patients with
 previously treated CD23+ and CD20+ relapsed CLL. Patients will receive treatment with either
 lumiliximab in combination with FCR or FCR alone.
Inclusion Criteria:

 -  Signed, written EC-approved informed consent form.

 -  Diagnosis of relapsed CD23+ and CD20+ B cell CLL as defined by NCI WG guidelines.

 -  Subjects who have received at least 1 but no more than 2 prior single agent or
 combination treatments for CLL.

 -  Rai Stage III or IV (Binet Stage C), or Rai Stage I or II (Binet Stage A or B) if
 determined to have disease progression as evidenced by rapid doubling of peripheral
 lymphocyte count, progressive lymphadenopathy, progressive splenomegaly, or B symptoms
 (Staging Criteria - Modified Rai).

 -  WHO Performance Status less than or equal to 2.

 -  Age greater than or equal to 18 years.

 -  Male and female subjects of reproductive potential must agree to follow accepted birth
 control methods during treatment and for 12 months after completion of treatment.

 -  Acceptable liver function: bilirubin less than or equal to 2.0 mg/dL (26 µmol/L); AST
 and ALT less than or equal to 2 times upper limit of normal.

 -  Acceptable hematologic status: platelet count greater than or equal to 50 x 10^9/L
 should be unsupported by transfusion; ANC greater than or equal to 1 x 10^9/L.

 -  Acceptable renal function: creatinine clearance calculated according to the formula of
 Cockcroft and Gault >50 mL/min; serum creatinine less than or equal to 1.5 times upper
 limit of normal.

 Exclusion Criteria:

 -  Subjects who are refractory to the following combination therapies: purine analogue +
 R, purine analogue + C, or purine analogue + CR. Refractory is defined as not
 achieving at least a PR for a minimum duration of 6 months as determined by treating
 physician. Purine analogues include fludarabine, pentostatin and cladribine.

 -  Radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or other
 investigational therapy within 4 weeks prior to Study Day 1.

 -  Previous exposure to lumiliximab or other anti-CD23 antibodies.

 -  Prior autologous or allogeneic BMT or hematopoetic stem cell transplant.

 -  Known infection with HIV, hepatitis B, or hepatitis C. Although testing for hepatitis
 B or hepatitis C is not mandatory, this should be considered for all subjects
 considered at high risk of hepatitis B or hepatitis C infection and in endemic areas.
 Subjects with any serological evidence of current or past hepatitis B or hepatitis C
 exposure are excluded unless the serological findings are clearly due to vaccination.

 -  Uncontrolled diabetes mellitus.

 -  Uncontrolled hypertension.

 -  Transformation to aggressive B-cell malignancy (e.g., large B cell lymphoma, Richter's
 Syndrome, or PLL).

 -  Secondary malignancy requiring active treatment (except hormonal therapy).

 -  Any medical condition that would require long-term use (>1 month) of systemic
 corticosteroids during study treatment. However, steroid use less than or equal to 1
 month is permissible during the study.

 -  Any serious nonmalignant disease or laboratory abnormality, which in the opinion of
 the Investigator and/or Sponsor would compromise protocol objectives.

 -  Active uncontrolled bacterial, viral, or fungal infections.

 -  New York Heart Association Class III or IV cardiac disease, myocardial infarction
 within the past 6 months prior to Study Day 1, unstable arrhythmia, or evidence of
 ischemia on ECG within 30 days prior to Study Day 1.

 -  Seizure disorders requiring anticonvulsant therapy.

 -  Severe chronic obstructive pulmonary disease with hypoxemia.

 -  Major surgery, other than diagnostic surgery, within 4 weeks prior to Study Day 1.

 -  Clinically active autoimmune disease.

 -  History of fludarabine-induced autoimmune cytopenia (as judged by the Investigator) or
 Coombs-positive haemolytic anemia.

 -  Pregnant or currently breastfeeding.