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Bortezomib

Phase 3

Mantle Cell Lymphoma | Small molecule | Oncology |Takeda Pharmaceutical Company Limited|Last Updated: Jul 12, 2018

Target and mechanism

ModalitySmall molecule

Also known as VELCADE

Success Probability

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Market & Valuation

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Trial Design

RandomizedACTIVE_CONTROLLEDBiomarker
Total Trials1
Total Enrollment487

FDA Designations

No designations recorded

Clinical trial landscape

Bortezomib · 6 trials · 6 indications

Phase 3 2Phase 2 2Phase 1 2
NCT00722137Study of the Combination of Rituximab, Cyclophosphamide, Doxorubicin, VELCADE, and Prednisone or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Newly Diagnosed Mantle Cell LymphomaMantle Cell Lymphoma
COMPLETED487 Analytics
NCT00111319VELCADE/Melphalan/Prednisone Versus Melphalan/Prednisone in Patients With Previously Untreated Multiple MyelomaMultiple Myeloma
COMPLETED- Analytics
PHASE3COMPLETED
Study of the Combination of Rituximab, Cyclophosphamide, Doxorubicin, VELCADE, and Prednisone or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Newly Diagnosed Mantle Cell Lymphoma
Mantle Cell LymphomaUnlock trial analytics
PHASE3COMPLETED
VELCADE/Melphalan/Prednisone Versus Melphalan/Prednisone in Patients With Previously Untreated Multiple Myeloma
Multiple MyelomaUnlock trial analytics

Study Endpoints

Primary Endpoints

Progression Free Survival (PFS)
Median duration of follow-up of 40 months

PFS was defined as the interval between the date of randomization and the date of progressive disease (PD) or death, whichever occurred first. PD was based on the assessment of an Independent Review Committee.

Time to progression
Progression-Free Survival (PFS) in Patients With Non-germinal Center B-cell-like (Non-GCB) Diffuse Large B-cell Lymphoma (DLBCL)
Median Follow-up of 34.3 months for RCHOP arm and 34.4 months for Vc-RCHOP arm

PFS is defined as the time in months from the date of randomization to the date of first documentation of progressive disease (PD) or death from any cause. The date of progression is the earliest date of a computed tomography/positron emission tomography (CT/PET) scan that shows evidence of PD. For a participant that has not progressed and is alive at the end of his/her study follow-up or at the time of start of an alternate therapy (whichever is first), PFS is censored at the last overall response assessment that is stable disease or better, and which is prior to the start of the alternate therapy, if any. Disease response was assessed using International Working Group (IWG)-revised response criteria for malignant lymphoma. PD= any new lesion or increase by \> 50% of previously involved sites from nadir.

Progression-Free Survival Rate
2 Years (Median Follow-up of 34.3 months for RCHOP arm and 34.4 months for Vc-RCHOP arm)

PFS is defined as the time in months from the date of randomization to the date of first documentation of progressive disease (PD) or death from any cause. The date of progression is the earliest date of a computed tomography/positron emission tomography (CT/PET) scan that shows evidence of PD. For a participant that has not progressed and is alive at the end of his/her study follow-up or at the time of start of an alternate therapy (whichever is first), PFS is censored at the last overall response assessment that is stable disease or better, and which is prior to the start of the alternate therapy, if any. Disease response was assessed using International Working Group (IWG)-revised response criteria for malignant lymphoma. PD= any new lesion or increase by \> 50% of previously involved sites from nadir. The progression-free survival rate is defined as the Kaplan-Meier (KM) estimate of progression-free survival at 2 years.

Area Under the Plasma Concentration-time Curve (AUC) 0-72 Hours
Cycle 3 day 14 (72 hours post last dose)
Maximum Tolerated Dose
5 weeks in once weekly (QW) dose cohorts and 3 weeks in twice weekly (BIW) dose cohorts

Maximum Tolerated Dose (MTD) was defined as the highest dose level that has 0/1 out of 6 patients experiences Dose Limited Toxicity (DLT). MTD is defined separately for QW and BIQ dose cohorts. DLT was defined as adverse events occurring during Cycle 1 and: (1) related to VELCADE, (2) Grade 4 thrombocytopenia or neutropenia, (3) Grade 3 or higher nonhematologic toxicity.

Subjects With Treatment Emergent Adverse Events
from first study-related procedure to 30 days after last dose of study medication

Treatment emergent adverse events observed during outcome measure time frame

Subjects With Serious Treatment Emergent Adverse Events
from first study-related procedure to 30 days after last dose of study medication

Serious treatment emergent adverse events observed during outcome measure time frame

Subjects Grade 3/4/5 Treatment Emergent Adverse Events
from first study-related procedure to 30 days after last dose of study medication

Grade 3/4/5 treatment emergent adverse events observed during outcome measure time frame. Grade is determined according to Common Terminology Criteria for Adverse Event (CTCAE) Version 3.0.

Subjects With Treatment Emergent Adverse Events Leading to Treatment Termination
from first study-related procedure to 30 days after last dose of study medication

Treatment emergent adverse events observed during outcome measure time frame leading to treatment termination

Secondary Endpoints

Time to Progression (TTP)
Median duration of follow-up of 40 months
Duration of Response
Median duration of follow-up of 40 months
Time to Next Anti-lymphoma Treatment (TTNT)
: Median duration of follow-up of 40 months
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
R-CHOPACTIVE_COMPARATORRituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, Vincristine 1.4 mg/m\^2, and Prednisone 100 mg/m\^2
VcR-CAPEXPERIMENTALRituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, VELCADE 1.3 mg/m\^2, and Prednisone 100 mg/m\^2
RCHOPACTIVE_COMPARATORRCHOP \[rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.
Vc-RCHOPEXPERIMENTALVc-RCHOP \[bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: bortezomib (VELCADE ®) 1.3 mg/m\^2 administered intravenous (IV) push on Days 1 and 4 of each cycle with RCHOP administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.
VELCADEEXPERIMENTALControl arm, bortezomib 1.3 mg/m\^2 on days 1, 4, 8, 11 over a 21-day treatment cycle.
VELCADE + rifampicinEXPERIMENTALTreatment Arm, bortezomib 1.3 mg/m\^2 on days 1, 4, 8, 11 over a 21-day treatment cycle, rifampicin 600 mg once daily days 4 to 10 in cycle 3.
VELCADE + dexamethasoneEXPERIMENTALTreatment arm, bortezomib 1.3 mg/m\^2 on days 1, 4, 8, 11 over a 21-day treatment cycle, dexamethasone 40 mg once daily days 1 to 4, and 9 to 12 in cycle 3.
1EXPERIMENTALVELCADE

Interventions

NameTypeDescription
Rituximab 375 mg/m^2DRUGIntravenous rituximab 375 mg/m\^2 on Day 1 of a 21-day (3 week) cycle for 6 cycles.
Cyclophosphamide 750 mg/m^2DRUGIntravenous cyclophosphamide 750 mg/m\^2 on Day 1 of a 21-day (3 week) cycle for 6 cycles
Doxorubicin 50 mg/m^2DRUGIntravenous doxorubicin 50 mg/m\^2 on Day 1 of a 21-day (3 week) cycle for 6 cycles
VELCADE 1.3 mg/m^2DRUGIntravenous VELCADE 1.3 mg/m\^2 on Days 1,4,8, and 11of a 21-day (3 week) cycle for 6 cycles
Prednisone 100 mg/m^2DRUGOral prednisone 100 mg/m\^2 on Day 1 to Day 5 of a 21-day (3 week) cycle for 6 cycles
Vincristine 1.4 mg/m^2DRUGIntravenous vincristine 1.4 mg/m\^2 on Day 1of a 21-day (3 week) cycle for 6 cycles. Maximum of 2 mg. Participants could receive 8 cycles if a response was initially documented at the Cycle 6 assessment.
bortezomibDRUG -
RituximabDRUGRituximab IV
CyclophosphamideDRUGCyclophosphamide IV
DoxorubicinDRUGDoxorubicin IV solution
VincristineDRUGVincristine IV
PrednisoneDRUGPrednisone tablet
VELCADEDRUG -
AlimtaDRUG -
bortezomib, rifampicinDRUGbortezomib 1.3 mg/m\^2 on days 1, 4, 8, 11 over a 21-day treatment cycle, rifampicin 600 mg once daily days 4 to 10 in cycle 3
bortezomib, dexamethasoneDRUGbortezomib 1.3 mg/m\^2 on days 1, 4, 8, 11 over a 21-day treatment cycle, dexamethasone 40 mg once daily days 1 to 4, and 9 to 12 in cycle 3
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites150

Inclusion Criteria: * Male or female patients 18 years or older (the patient must be at least the legal age limit to be able to give informed consent within the jurisdiction the study is taking place) * Diagnosis of mantle cell lymphoma MCL (Stage II, III or IV) as evidenced by lymph node histology...

Countries:United StatesAustriaBelgiumBrazilCanadaChileChinaColombiaCzechiaGermanyHungaryIndiaIsraelItalyMalaysiaMoroccoPhilippinesPolandPortugalRomaniaRussiaSingaporeSouth AfricaSpainTaiwanThailandTunisiaTurkey (Türkiye)UkraineUnited Kingdom
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Frequently asked questions about Bortezomib

What is VELCADE used for?

VELCADE is a small molecule drug being studied for Mantle Cell Lymphoma, Amyloidosis, and Non-Small Cell Lung Cancer. It is developed by Takeda Pharmaceutical Company Limited (TAK). The drug is currently in Phase 1 clinical development, though it has completed trials in later phases for these indications.

Who makes VELCADE?

VELCADE is developed by Takeda Pharmaceutical Company Limited, which trades under the ticker TAK. The drug is a small molecule therapeutic being investigated for rare diseases, including Amyloidosis, as well as for Mantle Cell Lymphoma and Non-Small Cell Lung Cancer.

What phase is VELCADE in?

VELCADE is currently in Phase 1 clinical development. It has completed one Phase 1 trial, one Phase 2 trial, and one Phase 3 trial. The drug is investigational and not yet approved, as it remains under clinical investigation for its studied indications.

What clinical trials is VELCADE in?

VELCADE has completed three clinical trials. NCT00298766 was a Phase 1/2 study in Amyloidosis with 70 participants. NCT00343720 was a Phase 2 study in Non-Small Cell Lung Cancer. NCT00722137 was a Phase 3 study in Mantle Cell Lymphoma with 487 participants. All trials are completed.

Is VELCADE the same as bortezomib?

VELCADE is the brand name for bortezomib, a small molecule drug. It is being studied for Mantle Cell Lymphoma, Amyloidosis, and Non-Small Cell Lung Cancer. The drug is developed by Takeda Pharmaceutical Company Limited and is currently in Phase 1 clinical development.

What does VELCADE target?

VELCADE is a small molecule drug that targets the proteasome, a cellular complex that degrades proteins. By inhibiting this target, it affects cancer cell growth. It is being studied for Mantle Cell Lymphoma, Amyloidosis, and Non-Small Cell Lung Cancer by Takeda Pharmaceutical Company Limited.