Ofatumumab fludarabine cyclophosphamide in relapsed CLL V1.0
Study OMB110913. A phase III, open label, randomized, multicenter trial of Ofatumumab added to Fludarabine vs.Fludarabine Cyclophosphamide combination in subjects with Relapsed Chronic Lymphocytic Leukemia.
Novartis Pharma AG
The primary objective of this study is to compare progression-free survival of subjects taking ofatumumab (a new monoclonal antibody which targets Chronic Lymphocytic Leukaemia cells) added tfluarabine-cyclophosphamide ( a purine and alkylator based therapy ) with subjects takinfluarabine-cyclophosphamide alone for the treatment of Relapsed Chronic Lymphocytic Leukaemia (CLL)fluarabine is a therapy currently approved for relapsed treatment of CLL & many studies of agents in combination witfluarbine (e.g. cyclophosphamide) have shown added activity. The addition of ofatumumab tfluarabine and cyclophosphamide is being investigated in this open-label randomised study, to see if it offers a more effective therapy with limited additional toxicities. Secondary objectives include an evaluation of subjects' overall well-being and quality of life.Approximately 352 eligible subjects, at least 80 in the UK, will be stratified and randomised in a 1:1 ratio to receive either ofatumumab as monthly iv infusions (300mg on day 1 and 1000mg on day 8 of cycle 1; 1000mg on day 1 of subsequent 28-day cycles) together witfluarabine (25mg/m2 IV) and cyclophosphamide (250mg/m2 IV) on Days 1-3 of each 28-day cycle for 6 cycles) or the same dose of Ifluarabine cyclophophamide alone. All subjects will receive 6 cycles of treatment and their disease will be assessed. Subjects' response will be measured by blood samples, lymph node examination, spleen and liver measurement and assessment of clinical symptoms performed monthly throughout the treatment phase and at one month post treatment and then every 3 months for up to 5 years. A bone marrow examination and CT scan will be performed to confirm complete remission at least 3 months after end of treatment.Safety assessments will be performed on a regular basis including haematology, biochemistry and adverse events.A sub-study will be conducted at selected sites in order to determine whether ofatumumab has an effect on the corrected QT interval (QTc) interval or ofluarabine or cyclophosphamide pharmacokinetics. All patients enrolled at participating sites are encouraged to enroll in the QTc and drug-drug interaction sub-study in order to avoid patient selection bias. A total of 50 subjects (25 per treatment arm) will participate in the sub-study.Objectives<ul> <li style="color: To evaluate the potential effect of ofatumumab on QTc interval</li> <li style="color: To evaluate the potential effect of ofatumumab ofluarabine or cyclophosphamide pharmacokinetics</li></ul>
North East - York Research Ethics Committee
Date of REC Opinion
14 Apr 2009
Further Information Favourable Opinion