Feasibility Study Of Adding Bortezomib to R-ICE Chemotherapy To Treat Relapsed/ Refractory Diffuse Large B-Cell Lymphoma

Sponsor
Singapore General Hospital
Study ID
NCT01226849
Phase
PHASE1
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
21 Years - N/A
Healthy Volunteers
Not accepted

Interventions

Study Details

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.

Key Dates

Start date
Nov 30, 2010
Status verified
Apr 2017
Primary completion
Nov 30, 2014
Completion
Nov 30, 2014

Study Design

Enrollment
6 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Single Arm
    bortezomib, rituximab, ifosphamide, etoposide, carboplatin Rituximab 375mg/m2 day 1 Etoposide 100mg/m2 day 1-3 Carboplatin AUC (5) max 800 days 2 Ifosfamide continuous infusion + Mesna 5/m2/24hr day2 Bortezomib 1.3mg/m2 days 1,4,8,11 G-CSF (SC) recommended

Primary Outcome Measure

To evaluate number of participants with adverse events with R-ICE plus bortezomib (VR-ICE) [ Time Frame: 2 years ]

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