GIMEMA CLL0809 Study (BendOfa)

Inclusion Criteria:

• Patients with CLL relapsing after an initial response (CR, PR ≥ 6 months) following no more than two prior treatment lines; or
• Patients with CLL refractory (SD, PD or CR/PR < 6 months) following no more than two prior treatment lines
• Patients requiring treatment according to 2008 revised IWCLL guidelines
• No more than 2 prior treatment lines
• Age older or equal to 18 years
• No active malignancies during the previous 5 years, with the exception of currently treated basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of any origin
• No prior treatment with conventional chemotherapy within the prior 4 weeks and with monoclonal antibodies within the prior 16 weeks
• ECOG performance status of ≤2 at study entry
• Laboratory test results within these ranges:

Serum creatinine ≤ 2 x UNL Creatinine clearance ≥ 50 ml/min (Cockcroft and Gault formula) Total bilirubin ≤ 2 x UNL (with exception of patients with Gilbert's syndrome) AST (SGOT) and ALT (SGPT) ≤ 2 x UNL non attributable to CLL AST (SGOT) and ALT (SGPT) ≤ 10 x UNL attributable to CLL

• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test prior to therapy and must agree to abstain from breastfeeding during study participation and for at least one year after discontinuation from the study.
• Signed written informed consent according to IGH/EU/GCP and Italian laws.

Exclusion Criteria:

• Concurrent use of other anti-cancer agents
• Use of any other experimental drug or therapy within 28 days of baseline
• Positive direct antiglobulin test (DAT) with clinical and laboratory signs of hemolysis and/or autoimmune thrombocytopenia
• Known transformation of CLL
• Known CNS involvement of CLL
• Known positivity for HIV or active HCV and HBV hepatitis.
• Active bacterial, viral or fungal infection requiring systemic anti-viral, antibiotic or anti-fungal therapy.
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones or stable chronic liver disease per investigator assessment)
• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she was to participate in the study or confounds the ability to interpret data from the study Concurrent use of other anti-cancer agents
• Use of any other experimental drug or therapy within 28 days of baseline
• Positive direct antiglobulin test (DAT) with clinical and laboratory signs of hemolysis and/or autoimmune thrombocytopenia
• Known transformation of CLL
• Known CNS involvement of CLL
• Known positivity for HIV or active HCV and HBV hepatitis.
• Active bacterial, viral or fungal infection requiring systemic anti-viral, antibiotic or anti-fungal therapy.
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones or stable chronic liver disease per investigator assessment)
• Concurrent use of other anti-cancer agents
• Use of any other experimental drug or therapy within 28 days of baseline
• Positive direct antiglobulin test (DAT) with clinical and laboratory signs of hemolysis and/or autoimmune thrombocytopenia
• Known transformation of CLL
• Known CNS involvement of CLL
• Known positivity for HIV or active HCV and HBV hepatitis.
• Active bacterial, viral or fungal infection requiring systemic anti-viral, antibiotic or anti-fungal therapy.
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones or stable chronic liver disease per investigator assessment)
• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she was to participate in the study or confounds the ability to interpret data from the study Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she was to participate in the study or confounds the ability to interpret data from the study