Clinical trial NCT01226849: Feasibility Study Of Adding Bortezomib to R-ICE Chemotherapy To Treat Relapsed/ Refractory Diffuse Large B-Cell Lymphoma
Official title: 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
Conditions: Diffuse Large B-Cell Lymphoma
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.
Interventions:
description: 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
name: bortezomib, rituximab, ifosphamide, etoposide, carboplatin
other_name: mabtera
rituxan,
velcade,
type: Drug
Study arms:
design_group_description: bortezomib, rituximab, ifosphamide, etoposide, carboplatin<br/>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
design_group_title: Single Arm
design_group_type: Experimental
Sponsor: Singapore General Hospital Pte Ltd.
Collaborators: Janssen-Cilag Ltd.
Drug name mappings:
name: 依托泊苷
lang: CN
name: Etoposide
lang: EN
name: エトポシド
lang: JP
name: 卡铂
lang: CN
name: Carboplatin
lang: EN
name: カルボプラチン
lang: JP
name: 异环磷酰胺
lang: CN
name: Ifosamide
lang: EN
name: イホスファミド
lang: JP
name: 硼替佐米
lang: CN
name: Bortezomib
lang: EN
name: ボルテゾミブ
lang: JP
name: 利妥昔单抗
lang: CN
name: Rituximab
lang: EN
name: リツキシマブ（遺伝子組換え）
lang: JP