Table 4 Targeted drugs and clinical trials related to the proteasome

From: Advances in targeted therapy for malignant lymphoma

Drug

Disease

Trial name

Phase

Status

ORR/CR

NCT#

Reference

Proteasome inhibitor

Bortezomib

A reversible proteasome inhibitor binding primarily with β5 and to a lesser extent, with β2 and β1 of the 20S proteasome particle

Bortezomib

Relapsed or refractory MCL

Bortezomib in subjects with relapsed or refractory mantle cell lymphoma

2

Completed

31%/8%

NCT00063713

281

Bortezomib, panobinostat

Relapsed or refractory PTCL

Study of bortezomib and panobinostat in treating patients with relapsed or refractory peripheral T-cell lymphoma

2

Completed

43%/22%

NCT00901147

282

Bortezomib, ibrutinib

MCL

Combination of ibrutinib and bortezomib to treat patients with mantle cell lymphoma

1/2

Recruiting

–

NCT02356458

–

Bortezomib, dexamethasone

Relapsed or refractory CTCL

Bortezomib plus dexamethasone therapy in patients with relapsed or refractory cutaneous T-cell lymphoma

2

Recruiting

–

NCT03487133

–

Bortezomib, GDP

Non-GCB DLBCL

A study of bortezomib plus GDP in the treatment of relapsed or refractory non-GCB DLBCL

2

Unknown

–

NCT02542111

–

Bortezomib, CHOP

Advanced aggressive T-NHLs/NKTCL

Bortezomib and CHOP in patients with advanced-stage aggressive T-cell or NK/T-cell lymphoma

1/2

Completed

NA

NCT00374699

–

VR-CAP vs. R-CHOP

Untreated MCL

Study of the combination of rituximab, cyclophosphamide, doxorubicin, bortezomib, and prednisone or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in patients with newly diagnosed mantle cell lymphoma

3

Completed

NA

NCT00722137

283

Bortezomib, dexamethasone, rituximab

Untreated WM

Bortezomib, low-dose dexamethasone, and rituximab in untreated Waldenström’s macroglobulinemia

2

Completed

85%/3%

NCT00981708

284

Bortezomib, dexamethasone, rituximab, and cyclophosphamide

WM

Efficacy of First-Line Dexamethasone, Rituximab, and Cyclophosphamide +/− Bortezomib for Patients With Waldenström’s Macroglobulinemia

3

Active, not recruiting

–

NCT01788020

–

Carfilzomib

A second-generation irreversible proteasome inhibitor binding to the β5 subunit of the 20S proteasome particle

Carfilzomib

Relapsed or refractory T-NHLs

Carfilzomib in treating patients with relapsed or refractory T-cell lymphoma

1

Completed

NA

NCT01336920

–

Carfilzomib, vorinostat

Relapsed or refractory lymphoma

Study of carfilzomib and vorinostat for relapsed or refractory lymphoma

1

Completed

NA

NCT01276717

–

Carfilzomib, romidepsin

Relapsed or refractory PTCL

Evaluation of the combination of romidepsin and carfilzomib in relapsed or refractory peripheral T-cell lymphoma patients

1/2

Recruiting

–

NCT03141203

–

Carfilzomib, umbralisib

Relapsed or refractory lymphoma

Carfilzomib and umbralisib in treatment of relapsed or refractory lymphoma

1/2

Recruiting

–

NCT02867618

–

Carfilzomib, rituximab

WM/MZL

Carfilzomib with or without rituximab in the treatment of Waldenström’s macroglobulinemia or marginal zone lymphoma

2

Completed

NA

NCT03269552

–

Carfilzomib, bendamustine, rituximab

Relapsed or refractory NHLs

Carfilzomib with bendamustine and rituximab in patients with relapsed or refractory non-Hodgkin’s lymphoma

1

Recruiting

–

NCT02187133

–

Carfilzomib, R-CHOP

DLBCL

Carfilzomib, rituximab, and combination chemotherapy in treating patients with diffuse large B-cell lymphoma

1/2

Recruiting

–

NCT02073097

–

Carfilzomib, R-ICE

Relapsed or refractory DLBCL

Carfilzomib, rituximab, ifosfamide, carboplatin, and etoposide in treating patients with relapsed or refractory stage I-IV diffuse large B-cell lymphoma

1/2

Recruiting

–

NCT01959698

–

Ixazomib

A reversible proteasome inhibitor binding to the β5 subunit of the 20S proteasome particle

Ixazomib

Relapsed or refractory FL

Phase 2 study of oral ixazomib in adult patients with relapsed or refractory follicular lymphoma

2

Completed

PSMB1 positice, 8.3%/0%; PSMB1 negative, 0%/0%

NCT01939899

–

Ixazomib

Relapsed or refractory CTCL/PTCL

Open-label, phase 2 study of ixazomib in patients with relapsed or refractory cutaneous and peripheral T-cell lymphoma

2

Completed

67%/NA

NCT02158975

–

Ixazomib, rituximab

Indolent B-NHLs

Ixazomib and rituximab in treating patients with indolent B-cell non-Hodgkin’s lymphoma

2

Recruiting

–

NCT02339922

–

Ixazomib, ibrutinib

Relapsed or refractory MCL

A study of ixazomib and ibrutinib in relapsed or refractory mantle cell lymphoma

1/2

Recruiting

–

NCT03323151

–

Ixazomib, romidepsin

Relapsed or refractory PTCL

Study of ixazomib and romidepsin in peripheral T-cell lymphoma

1/2

Recruiting

–

NCT03547700

–

lenalidomide, ixazomib, rituximab

High-risk indolent B-NHLs

Lenalidomide, ixazomib, and rituximab as frontline therapy for high-risk indolent B-cell lymphoma

1/2

Active, not recruiting

–

NCT02898259

–

  1. NA: ORR or CR are not available on the clinicaltrials.gov or from the published article, although the trial has been completed
  2. GDP gemcitabine, dexamethasone, and cisplatin, CHOP cyclophosphamide, doxorubicin, vincristine, prednisolone, VR-CAP bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone, R-CHOP rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone, R-ICE rituximab, ifosfamide, carboplatin, etoposide, PSMB1 proteasome subunit beta type-1
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