lumiliximab with fludarabine, cyclophosphamide, and rituximab (fcr) versus fcr alone in subjects with relapsed chronic lymphocytic leukemia (cll)

Conditions: Chronic Lymphocytic Leukemia

Summary: 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.


Eligibility criteria:
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.

Keywords: cd23+/cd20+ b-cell cll cll