Feasibility Study Of Adding Bortezomib to R-ICE Chemotherapy To Treat Relapsed/ Refractory Diffuse Large B-Cell Lymphoma
Status:
Completed
Trial end date:
2014-11-01
Target enrollment:
Participant gender:
Summary
Incorporation of rituximab to conventional chemotherapy (R-CHOP) has revolutionalized the
frontline treatment of diffuse large B-cell lymphoma (DLBCL), one of the commonest subtype of
lymphoma. Although the majority of patients are cured, there still remains a substantial
number patients (20-30%) who will relapse despite upfront R-CHOP therapy. Recent studies have
informed that in the rituximab era, the ability to salvage patients with relapsed DLBCL with
the conventional salvage regimens like R-ICE or R-DHAP is significantly poorer than expected.
For a patients who has been exposed to rituximab in the frontline, the response rate of
conventional salvage chemotherapy is now a mere 51% (Coral Study). This suggests that
relapses after rituximab exposure are more severe, strongly implying the presence of
rituximab-resistant disease in additional to the selection of more aggressive subtypes of
DLBCL which R-CHOP may not have a significant impact on. As R-CHOP is currently the frontline
standard of care, more has to be done to augment the current available salvage regimens as a
response rate of 51% is unacceptable.
Incorporation of agents targeting rituximab-resistance and also the more aggressive subtype
of DLBCL ( ABC subtype) is prudent in the salvage regimen. Bortezomib, a targeted novel agent
has potent anti-tumor effects on its own. It has also been show clinically to be able to
overcome the adverse risk conferred by the ABC subtype of DLBCL. In addition, preclinical
studies have also demonstrated that bortezomib may enhance the biologic activity of rituximab
through upregulation of CD20, the target of rituximab.
The investigators hypothesize that adding bortezomib to salvage regimen of DLBCL will be more
efficacious. Increasing the response rate will then allow more eligible patients to go on to
autologous stem cell transplantation. The investigators intend to test the tolerability and
efficacy of the combination of bortezomib with the R-ICE regimen, and attempt to correlate
responses with histopathological and gene expression studies of tumor specimens.