Phase IV Observational Study in Chronic Lymphocytic Leukemia
Phase IV Observational Study in Chronic Lymphocytic Leukemia
B-cell chronic lymphocytic leukemia (CLL) is a subtype of mature peripheral B-cell neoplasms,
 characterized by the accumulation of circulating malignant lymphocytes that typically express
 cell surface markers CD5, CD20, and CD23. It is the most common type of leukemia in adults in
 Western Europe and in the US. The median age at diagnosis is 65-70 years, with a male to
 female ratio of 2:1. Initially, most patients present with asymptomatic lymphocytosis and do
 not need cytoreductive therapy. Patients with active disease are characterized by a
 lymphocyte doubling time of less than 6 months, or progressive, even massive lymphadenopathy,
 hepatosplenomegaly, anemia and thrombocytopenia. Constitutional symptoms such as fever, night
 sweats, unintended weight loss, and extreme fatigue are common in advanced disease and can
 significantly impact quality of life. CLL also causes relative immunosuppression that
 increases the risk of infections that are ultimately the major cause of death in this patient
 population. Median survival at diagnosis ranges from 5 to 20+ years depending on risk
 factors, but is only 6 to 14 months for patients with CLL refractory to available therapies.

 Arzerra (ofatumumab) is a human monoclonal antibody (IgG1) that binds specifically to a
 distinct epitope encompassing both the small and large extracellular loops of the CD20
 molecule. The CD20 molecule is a transmembrane phosphoprotein expressed on B lymphocytes from
 the pre-B to mature B lymphocyte stage and on B-cell tumors.

 Arzerra is designated as an orphan medicinal product in the European Union (EU) for treatment
 of chronic lymphocytic leukemia. The Committee for Orphan Medicinal Products (COMP) concluded
 that chronic lymphocytic leukemia was estimated to be affecting approximately 3.5 in 10,000
 persons in the Community at the time the application was made (June 2008) and that the
 condition is chronically debilitating and life-threatening, in particular due to poor
 long-term survival in high-risk patients.

 Arzerra was given a conditional approval in the EU on April 19, 2010. The approved indication
 in the EU for the product is treatment of CLL in patients refractory to fludarabine and
 alemtuzumab. A specific obligation for this conditional approval was an agreement by GSK to
 conduct a post-marketing observational study in CLL patients receiving Arzerra. The data from
 this study is intended to enhance the evidence of the safety and efficacy of Arzerra as it is
 used in clinical practice, and once final data are available, together with results of a
 second specific obligation study, will support the transition from conditional to a full
 approval of Arzerra in the EU.

 The objective of this observational study is to provide additional data to confirm the safety
 profile and efficacy of Arzerra for CLL patients treated in clinical practice.

 Particular data of interest are: co-morbidities (specific chronic disease diagnoses),
 concomitant medications, disease (CLL) characteristics, prior treatment regimens, adverse
 events, reasons for discontinuation of Arzerra therapy, Arzerra response, progression free
 survival, and overall survival.

 This is an observational, non-interventional, medical record review study in CLL patients. A
 total of 100 patients with CLL who have previously received Arzerra, whether alive or
 deceased, and have either completed the full course of Arzerra therapy or discontinued
 treatment early will be eligible to participate in the study. Centers across Europe who are
 members and non members of the European Research Initiative of CLL (ERIC) and treat CLL
 patients will participate in the study.

 CLL patients newly initiating Arzerra who are still undergoing the treatment phase and
 patients having been treated with Arzerra in phase II or phase III clinical trials will be
 excluded.

 For patients who have completed approximately 1 year or more of follow up since Arzerra
 initiation, data on response to Arzerra, adverse events during treatment and subsequent to
 treatment, patient status, progression free survival and overall survival covering the period
 up to approximately one-year post-drug initiation will be collected. For patients who have
 not completed approximately l year of follow-up since Arzerra initiation, including those who
 have been lost to follow up or died prior to one year or have not yet had a full year to
 elapse in calendar time, similar data will be collected at the point in time at the last
 available patient contact with the physician using information in the record. After approach
 for informed consent from the patient or next of kin for patients who have died to review the
 medical record, no interaction with the patient will occur.
Inclusion Criteria:

 -  All CLL patients who have previously received Arzerra, whether alive or deceased

 -  Patients who have either completed the full course of Arzerra therapy or discontinued
 treatment early

 Exclusion Criteria:

 -  CLL patients newly initiating Arzerra

 -  Patients having been treated with Arzerra in phase II or phase III clinical trials