An Open-Label, Pilot Study To Investigate Feasibility and Safety Of Using Bortezomib, Rituximab, Ifosfamide, Carboplatin, Etoposide As Salvage Regime In Previously Treated Patients With Diffuse Large B-Cell Lymphoma
The most commonly used regimen for relapsed/refractory diffuse large B-cell lymphoma (DLBCL)
is the R-ICE regime (rituximab, ifosphamide, cisplatin and etoposide). It was previously
reported to give an overall response rate (RR) of close to 70%, and a complete response rate
of 53%. As most DLBCL patients are now treated in the frontline with R-CHOP regimen, the
validity of RRs with R-ICE needs to be reevaluated. Results of the CORAL study, a
prospective randomized phase III trial comparing R-DHAP vs R-ICE in relapsed DLBCL were
recently presented. It was shown that there was no difference in RR between R-ICE and
R-DHAP. However, the RR of patients who had received prior rituximab in the frontline
setting was significantly lower at 51%, compared with rituximab-naïve patients at 83%. This
suggests that relapses after rituximab exposure are more severe. In addition to the risk of
more aggressive subtype of DLBCL (activated B-cell [ABC]) that may not be abrogated by
rituximab, the presence of rituximab-resistant disease is also strongly implicated. As
R-CHOP is currently the frontline standard of care, more has to be done to augment the
current available salvage regimens. Incorporation of agents targeting the activated B-cell
(ABC)subtype and rituximab-resistance is prudent in the salvage regimen. Bortezomib, a
proteosome inhibitor impacts on many cellular processes relevant to the pathogenesis of
DLBCL, including inhibition of nuclear factor-kappa B. Preclinical studies have also
demonstrated that bortezomib displayed significant antitumor activity against various
lymphomas, and in particular the ABC subtype of DLBCL. It is also capable of enhancing the
biologic activity of rituximab through upregulation of CD20 in preclinical studies.
Demonstration of synergism in these 2 agents, in part due to their dependence on overlapping
pathways, suggests that they should be explored as a combination.
On this basis, the investigators aim to conduct a pilot study of adding intravenous
bortezomib to R-ICE as a salvage regime for adult patients with relapsed/refractory DLBCL.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To evaluate number of participants with adverse events with R-ICE plus bortezomib (VR-ICE)
To evaluate the feasibility, safety and maximum tolerated dose (MTD) of R-ICE plus bortezomib (VR-ICE) in previously treated patients with DLBCL.
Daryl Tan, MBBS MRCP
Singapore General Hospital
Singapore: Health Sciences Authority