Single Arm NCRI Feasibility Study of CHOP in Combination With Ofatumumab in Induction and Maintenance for Patients With Newly Diagnosed Richter's Syndrome
Richter's Syndrome (RS) is a high-grade transformation that occurs in 5-15% of patients with
B cell chronic lymphocytic leukaemia (B-CLL). RS is a complication of B-CLL in which the
leukemia changes into a fast-growing diffuse large B cell lymphoma (DLBCL). The pathogenesis
(mechanism by which the disease is caused) of RS is poorly understood and predictors of
transformation and response to treatment are unknown. Management of RS remains
unsatisfactory; the mean overall survival of patients treated with conventional
chemo-immunotherapy such as CHOP-R is 8 months from the end of treatment.
CHOP is the acronym for a chemotherapy regimen, cyclophosphamide, hydroxydaunorubicin
(doxorubicin), Oncovin (vincristine), and prednisone/prednisolone) and the R stands for the
monoclonal antibody, Rituximab. Ofatumumab, a next generation monoclonal anti CD20 antibody,
has proven single agent activity in relapsed/refractory B-CLL and other non-Hodgkin
lymphomas. In addition, it has shown a favourable safety profile in the maintenance setting.
Therefore, we propose to evaluate Ofatumumab in combination with CHOP in induction and
maintenance treatment of patients with RS.
The primary objective of the study will be to evaluate overall response rate (ORR) to CHOP-O
(CHOP chemotherapy plus Ofatumumab) according to the Revised Response Criteria for Malignant
Secondary objectives will be feasibility of recruitment, progression free survival and
overall survival, the clinical benefit and changes in patient reported outcome measures,
safety and tolerability.
This is a multi-centre non-randomised Phase II National Cancer Research Institute (NCRI)
feasibility study in 35 patients with newly diagnosed Richter's Syndrome in the UK. CHOP-O
will be given for six cycles followed by six cycles of Ofatumumab maintenance treatment
every eight weeks and a three months follow-up period. The total duration of recruitment
will be 24 months starting from the opening of the first site.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Objective response as defined by the revised response criteria for malignant lymphoma (Cheson et al, JCO, Vol 25, No 5, 2007). Patients will be classified as responders/non-responders as follows: complete remission (CR), nodular partial remission (nPR) and partial remission (PR) are classified as responders; while stable disease (SD) and progressive disease (PD) are classified as non-responders. Non-evaluable patients will be classified as non-responders.
Anna Schuh, MD, PhD, MRCP, FRCPath
Oxford University Hospitals NHS Trust
United Kingdom: Medicines and Healthcare Products Regulatory Agency