Assessment of Efficacy and Safety of Front-line Fludarabine, Cyclophoshamide and Ofatumumab Chemoimmunotherapy in Young Patients With Chronic Lymphocytic Leukemia. (CLL0911)

Inclusion Criteria:

• B-cell CLL diagnosis by 2008 revised IWCLL criteria.
• Treatment requirement according to the 2008 revised IWCLL criteria.
• No previous treatment.
• Age > 18 year and . 65 years.
• ECOG performance status of 0-1 at study entry and CIRS score .6.
• Adequate renal function (creatinine clearance.60 ml/min estimated using the Cockcroft-Gaultequation) .
• For male and female subjects of childbearing potential, agreement to use effective contraception.
• Signed written informed const according to ICH/EU/GCP and national local laws.

Exclusion Criteria:

• Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease and/or laboratory abnormality which in the opinion of the investigator may represent a risk for the patient and/or that would prevent the subject from signing the informed consent form.
• Pregnant or lactating females.
• Known positive serology for HIV.
• Positive serology for Hepatitis B (HBV) defined as a positive test for HBsAg and HBV-DNA.
• HCV-RNA positive.
• Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection, tuberculosis and active hepatitis.
• History of tuberculosis within the last five years or recent exposure to tuberculosis equal to or less than 6 months.
• Known presence of alcohol and/or drug abuse.
• Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to the inclusion in the study, congestive heart failure (NYHA III-IV), arrhythmia unless controlled by therapy.. grade 2 neuropathy; history of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae.
• Uncontrolled autoimmune hemolytic anemia or thrombocytopenia.

• One or more laboratory abnormalities:

  1. Calculated creatinine clearance (Cockroft-Gault)<60mL/min.
  2. Absolute granulocyte count <1500/ƒÊL not disease related.
  3. Platelet count < 75000/ƒÊL not disease related.
  4. GOT, GPT, GT, alkaline phosphatase > 1,5 x upper limit of normal value unless due to disease involvement); serum bilirubin >1.5mg/dL, subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones)
• Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to enrollment, whichever is longer, or currently participating in any other interventional clinical study
• Other past or current malignancy. Subjects who have been free of malignancy for at least 5 years, or have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible.