Feasibility Study of R-CHOP Plus Bevacizumab in Patients With Diffuse Large B Cell Lymphoma (DLBCL)
Non-Hodgkin's lymphoma is increasing in incidence with more than 287,000 cases world-wide
and 9000 cases in UK diagnosed each year. DLBCL is the most frequently occurring NHL,
constituting approximately 31% of all non-Hodgkin's lymphomas.
Rituximab-CHOP chemotherapy has shown clinical efficacy and is regarded as standard
treatment in patients with DLBCL. NICE has recently approved the use of rituzimab in
combination with CHOP for all newly diagnosed patients with DLBCL stage II-IV.
Angiogenesis plays an important role in the pathophysiology of both solid tumours and
hematologic malignancies. Vascular endothelial growth factor (VEGF) is the most important
pro-angiogenic factor involved in normal and pathologic angiogenesis and studies have also
implicated VEGF in lymphomagenesis. Elevated VEGF gene expression correlates with diffuse
large B cell lymphoma subtypes of poor prognosis on microarray analysis. In patients with
lymphoma, high circulating serum VEGF levels have been strongly associated with poor
clinical outcomes independent of other predictive factors.
Bevacizumab is a humanized monoclonal antibody that binds to VEGF thus preventing binding to
its receptors thus inhibiting the downstream pathways dependent on receptor stimulation.
Bevacizamab has shown activity in solid tumours (colorectal, renal, breast and non-small
cell lung cancer) and early results suggest that the combination of R-CHOP plus bevacizamab
is feasible in patients with non Hodgkin's lymphoma.
Patients will be treated with a minimum of 6 cycles of treatment. A further 2 cycles, to a
total of 8 cycles, may be administered if continuing response to treatment has been
documented but residual disease is still detectable on restaging after 6 cycles. Each cycle
of treatment is 21 days.
Follow up - a) Clinic visit with physical examination at 3, 6, 9, 12, 18 and 24 months after
completion of R-CHOP-B, then annually.
b) CT scan of chest, abdomen and pelvis at 3 months and 1 year after finishing treatment.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
The primary endpoint of this study is cardiac and bevacizumab-specific toxicity. Toxicities will be evaluated according to the NCI Common Toxicity Criteria for Adverse Events v3.0
Royal Marsden NHS Foundation Trust
United Kingdom: Medicines and Healthcare Products Regulatory Agency