Phase IV Observational Study in Chronic Lymphocytic Leukemia
Status:
Completed
Trial end date:
2012-11-01
Target enrollment:
Participant gender:
Summary
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.