A Study Evaluating Venetoclax (ABT-199) in Multiple Myeloma Subjects Who Are Receiving Bortezomib and Dexamethasone as Standard Therapy
Bellini
A Phase 3, Multicenter, Randomized, Double Blind Study of Bortezomib and Dexamethasone in Combination With Either Venetoclax or Placebo in Subjects With Relapsed or Refractory Multiple Myeloma Who Are Sensitive or Naïve to Proteasome Inhibitors
2 other identifiers
interventional
291
16 countries
97
Brief Summary
This was a Phase 3, multicenter, randomized, double blind, placebo-controlled study evaluating the efficacy and safety of venetoclax plus bortezomib and dexamethasone in participants with relapsed or refractory multiple myeloma who are considered sensitive or naïve to proteasome inhibitors and received 1 to 3 prior lines of therapy for multiple myeloma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jul 2016
Longer than P75 for phase_3
97 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 20, 2016
CompletedFirst Posted
Study publicly available on registry
April 29, 2016
CompletedStudy Start
First participant enrolled
July 11, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 15, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
August 15, 2022
CompletedResults Posted
Study results publicly available
August 22, 2023
CompletedAugust 22, 2023
August 1, 2023
4.7 years
April 20, 2016
July 12, 2023
August 18, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-free Survival (PFS)
PFS is defined as the number of days from the date the participant was randomized to the date of the first documented progressive disease (PD) as determined by an Independent Review Committee (IRC) or death due to any cause, whichever occurs first. PFS was analyzed by Kaplan-Meier methodology.
Median duration of follow-up was 28.6 months for the venetoclax group and 28.6 months for the placebo group
Secondary Outcomes (11)
Very Good Partial Response (VGPR) or Better Response Rate
Response was assessed at Cycle 1, Day 1, and on Day 1 of every cycle thereafter; median time on follow-up was 28.6 months for the venetoclax group and 28.6 months for the placebo group
Progression-Free Survival (PFS) in Participants With High B-cell Lymphoma 2 (BCL-2) Expression
Median duration of follow-up was 28.6 months for the venetoclax group and 28.6 months for the placebo group
Duration of Response (DOR)
Response was assessed at Cycle 1, Day 1, and on Day 1 of every cycle thereafter; median time on follow-up was 28.6 months for the venetoclax group and 28.6 months for the placebo group
Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain
Baseline; Cycle 3 (Cycles 1 - 8 are 21 days, Cycles 9 and beyond are 35 days) through Cycle 47, collected on Day 1 of every other cycle and at the Treatment Completion Visit (TCV) while participant is on treatment
Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
Baseline; Cycle 3 (Cycles 1 - 8 are 21 days, Cycles 9 and beyond are 35 days) through Cycle 47, collected on Day 1 of every other cycle and at the Treatment Completion Visit (TCV) while participant is on treatment
- +6 more secondary outcomes
Study Arms (2)
Venetoclax + Bortezomib and Dexamethasone
EXPERIMENTALCycles 1-8: Venetoclax 800 mg orally every day (QD) on Days 1 - 21 plus bortezomib 1.3 mg/m\^2 subcutaneously or IV on Days 1, 4, 8 \& 11 and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 \& 12; Cycles 9 and beyond: Venetoclax 800 mg orally every day (QD) on Days 1 - 35 plus bortezomib 1.3 mg/m\^2 subcutaneously or IV on Days 1, 8, 15 and 22 and dexamethasone 20 mg orally on Days 1, 2, 8, 9, 15, 16, 22 and 23
Placebo + Bortezomib and Dexamethasone
PLACEBO COMPARATORCycles 1-8: Placebo (to match venetoclax 100 mg tablet) 800 mg orally every day (QD) on Days 1 - 21 plus bortezomib 1.3 mg/m\^2 subcutaneously or IV on Days 1, 4, 8 \& 11 and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 \& 12; Cycles 9 and beyond: Placebo (to match venetoclax 100 mg tablet) 800 mg orally every day (QD) on Days 1 - 35 plus bortezomib 1.3 mg/m\^2 subcutaneously or IV on Days 1, 8, 15 and 22 and dexamethasone 20 mg orally on Days 1, 2, 8, 9, 15, 16, 22 \& 23
Interventions
Participants self-administered venetoclax tablets by mouth QD in combination with bortezomib. Venetoclax was to be given before other agents administered on the same day, if applicable. Each venetoclax dose was to be taken all at one time with approximately 240 mL of water within 30 minutes after completion of breakfast or the subject's first meal of the day. Tablets were to be swallowed whole and must not have been broken, chewed, or crushed. On days that pre-dose PK sampling was required, dosing occurred at the clinic to facilitate PK sampling.
Bortezomib (subcutaneous injection \[preferred\] or IV) was given following administration of venetoclax or placebo in Cycles 1 -8 on Days 1, 4, 8 and 11, and for Cycles 9 and beyond, on Days 1, 8, 15 and 22 and was to be administered per the prescribing information. The route of administration was to stay the same during the study.
Dexamethasone was to be given orally, administered per the prescribing information, the day of bortezomib dosing and the following day, given the protocol-defined dosing window (bortezomib dosing window is ± 1 day) is maintained. If bortezomib was interrupted or a dose is skipped, dexamethasone was to be administered as scheduled per protocol (unless dexamethasone was interrupted due to toxicity).
Participants self-administered placebo tablets by mouth QD in combination with bortezomib. Placebo was to be given before other agents administered on the same day, if applicable. Each placebo dose was to be taken all at one time with approximately 240 mL of water within 30 minutes after completion of breakfast or the subject's first meal of the day. Tablets were to be swallowed whole and must not have been broken, chewed, or crushed. On days that pre-dose PK sampling was required, dosing occurred at the clinic to facilitate PK sampling.
Eligibility Criteria
You may qualify if:
- Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2
- Participant has documented relapsed or progressive multiple myeloma on or after any regimen or who are refractory to the most recent line of therapy. Relapsed myeloma is defined as previously treated myeloma that progresses and requires initiation of salvage therapy, but does not meet the criteria for refractory myeloma. Refractory myeloma is defined as disease that is nonresponsive (failure to achieve minimal response or development of progressive disease \[PD\]) while on primary or salvage therapy, or progresses within 60 days of last therapy.
- Participant must have received prior treatment with at least one, but no more than three, prior lines of therapy for multiple myeloma. A line of therapy consists of ≥ 1 complete cycle of a single agent, a regimen consisting of combination of several drugs, or a planned sequential therapy of various regimens.
- Prior treatment with bortezomib or other proteasome inhibitor is allowed, provided ALL of the following criteria are met: Disease is NOT refractory to any proteasome inhibitor, defined as no disease progression (i.e., PD, per International Myeloma Working Group \[IMWG\] or European Society for Blood and Marrow Transplantation \[EBMT\] criteria) while receiving proteasome inhibitor therapy or within 60 days after the last dose, AND best response achieved with any proteasome inhibitor therapy (alone or in combination) was at least a Partial Response (PR), AND participant did not discontinue any proteasome inhibitor due to intolerance or ≥ Grade 3 related toxicity.
- Participant has measurable disease at Screening, defined as at least one of the following: Serum M-protein ≥ 0.5 g/dL, OR Urine M-protein ≥ 200 mg in 24-hours, OR serum immunoglobulin free light chain (FLC) ≥ 10 mg/dL provided serum FLC ratio is abnormal.
You may not qualify if:
- Participant is refractory to any proteasome inhibitor, defined as progression on or within 60 days of the last dose of a proteasome inhibitor-containing regimen.
- Participant has had prior treatment with proteasome inhibitor within 60 days prior to first dose of study drug.
- Participant has any of the following conditions:
- Non-secretory multiple myeloma, active plasma cell leukemia i.e., either 20% of peripheral white blood cells or greater than 2.0 X 10\^9/liter (L) circulating plasma cells by standard differential, Waldenstrom's macroglobulinemia, amyloidosis, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), known Human Immunodeficiency Viral (HIV) infection, active hepatitis B or C infection based on blood screen tests, significant cardiovascular disease, including uncontrolled angina, severe or uncontrolled arrhythmia, recent myocardial infarction within 6 months of randomization, or congestive heart failure New York Heart Association (NYHA) Class ≥ 3, major surgery within 4 weeks prior to randomization, acute infections requiring parenteral therapy (antibiotic, antifungal, or antiviral) within 14 days prior to randomization, peripheral neuropathy ≥ Grade 3 or ≥ Grade 2 with pain within 2 weeks prior to randomization, uncontrolled diabetes or uncontrolled hypertension within 14 days prior to randomization, any other medical condition that, in the opinion of the Investigator, would adversely affect the participant's participation in the study
- Participant has a history of other active malignancies, including myelodysplastic syndrome (MDS), within the past 3 years prior to study entry, with the following exceptions: Adequately treated in situ carcinoma of the cervix uteri or the breast, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin, prostate cancer Gleason grade 6 or lower AND with stable Prostate Specific Antigen (PSA) levels off treatment, previous malignancy with no evidence of disease confined and surgically resected (or treated with other modalities) with curative intent and unlikely to impact survival during the duration of the study
- If participant had prior allogeneic stem cell transplant (SCT), participant has evidence of ongoing graft-versus-host disease (GvHD)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AbbVielead
- Genentech, Inc.collaborator
Study Sites (97)
Rocky Mountain Regional VA Medical Center/Eastern Colorado Health Care System /ID# 156524
Aurora, Colorado, 80045, United States
Univ of Colorado Cancer Center /ID# 149130
Aurora, Colorado, 80045, United States
Duke Cancer Center /ID# 149099
Durham, North Carolina, 27710-3000, United States
Gabrail Cancer Center Research /ID# 149098
Canton, Ohio, 44718, United States
Royal Prince Alfred Hospital /ID# 149108
Camperdown, New South Wales, 2050, Australia
Concord Repatriation General Hospital /ID# 149106
Concord, New South Wales, 2139, Australia
Liverpool Hospital /ID# 149110
Liverpool, New South Wales, 2170, Australia
Royal Brisbane and Women's Hospital /ID# 149105
Herston, Queensland, 4029, Australia
The Queen Elizabeth Hospital /ID# 149104
Woodville South, South Australia, 5011, Australia
Royal Hobart Hospital /ID# 149111
Hobart, Tasmania, 7000, Australia
Box Hill Hospital /ID# 149112
Box Hill, Victoria, 3128, Australia
Peter MacCallum Cancer Ctr /ID# 149107
Melbourne, Victoria, 3000, Australia
Alfred Health /ID# 150085
Melbourne, Victoria, 3004, Australia
Fiona Stanley Hospital /ID# 148967
Murdoch, Western Australia, 6150, Australia
Perth Blood Institute Ltd /ID# 148966
Nedlands, Western Australia, 6009, Australia
Hospital das Clinicas da Universidade Federal de Goiás /ID# 149290
Goiânia, Goiás, 74605-020, Brazil
Liga Norte Riograndense Contra o Câncer /ID# 149023
Natal, Rio Grande do Norte, 59075-740, Brazil
Hospital Sao Lucas da PUCRS /ID# 149027
Porto Alegre, Rio Grande do Sul, 90610-000, Brazil
Clinica Sao Germano /ID# 149851
São Paulo, São Paulo, 04537-080, Brazil
Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA) /ID# 149020
Rio de Janeiro, 20231-050, Brazil
Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo /ID# 149025
São Paulo, 05403-000, Brazil
Victoria Hospital /ID# 149846
London, Ontario, N6A 4L6, Canada
CISSS de la Monteregie /ID# 149844
Greenfield Park, Quebec, J4V 2H1, Canada
CHU Limoges - Dupuytren 1 /ID# 149292
Limoges, Franche-Comte, 87042, France
CHU de Nantes, Hotel Dieu -HME /ID# 149294
Nantes, Pays de la Loire Region, 44000, France
Duplicate_Centre Hospitalier Lyon Sud /ID# 149300
Pierre-Bénite, Rhone, 69495, France
CHRU de Brest - Hopital Morvan /ID# 149299
Brest, 29200, France
CHU Grenoble - Hopital Michallon /ID# 149301
La Tronche, 38700, France
Charite Universitaetsmedizin Berlin - Campus Mitte /ID# 148949
Berlin, 10117, Germany
Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 148948
Dresden, 01307, Germany
Asklepios Klinik Altona /ID# 150116
Hamburg, 22763, Germany
Debreceni Egyetem Klinikai Kozpont /ID# 152517
Debrecen, Hajdú-Bihar, 4032, Hungary
Somogy Megyei Kaposi Mor Oktato Korhaz /ID# 152516
Kaposvár, Somogy County, 7400, Hungary
Semmelweis Egyetem /ID# 152519
Budapest, 1085, Hungary
Semmelweis Egyetem /ID# 152520
Budapest, 1085, Hungary
Del-pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet /ID# 152518
Budapest, 1097, Hungary
University Hospital Galway /ID# 149061
Galway, H91 YR71, Ireland
Azienda Ospedaliero-Universitaria Policlinico Umberto I /ID# 148939
Rome, Lazio, 00161, Italy
Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona /ID# 148942
Ancona, 60126, Italy
IRCCS Azienda Ospedaliero-Universitaria di Bologna /ID# 148936
Bologna, 40138, Italy
Ospedale S.Eugenio /ID# 148938
Rome, 00144, Italy
A.O.U. Città della Salute e della Scienza di Torino/Ospedale Molinette /ID# 148943
Turin, 10126, Italy
Nagoya City University Hospital /ID# 150943
Nagoya, Aichi-ken, 467-8602, Japan
Kyushu University Hospital /ID# 150896
Fukuoka, Fukuoka, 812-8582, Japan
Ogaki Municipal Hospital /ID# 150783
Ogaki-shi, Gifu, 503-8502, Japan
Gunma University Hospital /ID# 150275
Maebashi, Gunma, 371-8511, Japan
National Hospital Organization Shibukawa Medical Center /ID# 150281
Shibukawa-shi, Gunma, 377-0280, Japan
Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital /ID# 150242
Hiroshima, Hiroshima, 730-8619, Japan
Kobe City Medical Center General Hospital /ID# 150944
Kobe, Hyōgo, 650-0047, Japan
National Hospital Organization Mito Medical Center /ID# 151051
Higashi Ibaraki-gun, Ibaraki, 311-3193, Japan
Duplicate_Kyoto Prefectural University of Medicine /ID# 150719
Kyoto, Kyoto, 602-8566, Japan
JCHO Kyoto Kuramaguchi Medical /ID# 150781
Kyoto, Kyoto, 603-8151, Japan
Tohoku University Hospital /ID# 150945
Sendai, Miyagi, 9808574, Japan
Okayama Medical Center /ID# 150717
Okayama, Okayama-ken, 701-1192, Japan
Japanese Red Cross Osaka Hospital /ID# 150716
Osaka, Osaka, 543-8555, Japan
Saitama Medical Center /ID# 151044
Kawagoe-shi, Saitama, 350-8550, Japan
Tochigi Cancer Center /ID# 150192
Utsunomiya, Tochigi, 320-0834, Japan
National Cancer Center Hospital /ID# 151039
Chuo-ku, Tokyo, 104-0045, Japan
The Cancer Institute Hospital Of JFCR /ID# 150780
Koto-ku, Tokyo, 135-8550, Japan
Japanese Red Cross Medical Center /ID# 149902
Shibuya-ku, Tokyo, 150-8935, Japan
National Hospital Organization Disaster Medical Center /ID# 150784
Tachikawa-shi, Tokyo, 190-0014, Japan
Kuzbass Regional Clinical Hospital /ID# 148955
Kemerovo, Kemerovo Oblast, 650099, Russia
State Institution of Health of the Ryazan Regional Clinical Hospital /ID# 148956
Ryazan, Ryazan Oblast, 390039, Russia
LLC Novaya Klinika /ID# 148974
Pyatigorsk, Stavropol Kray, 357500, Russia
Central Clinical Hospital RZHD Medicine /ID# 148954
Moscow, 129128, Russia
Clinical Oncology Dispensary of Omsk /ID# 148953
Omsk, 644013, Russia
Samara State Medical University /ID# 148952
Samara, 443099, Russia
Bashkir State Medical University /ID# 151206
Ufa, 450008, Russia
National Cancer Center /ID# 150889
Goyang, Gyeonggido, 10408, South Korea
Seoul National University Bundang Hospital /ID# 150888
Seongnam, Gyeonggido, 13620, South Korea
Duplicate_Yonsei University Health System, Severance hospital. /ID# 150891
Seoul, Seoul Teugbyeolsi, 03722, South Korea
Chonnam National University Hospital /ID# 150894
Gwangju, 61469, South Korea
Gachon University Gil Medical Center /ID# 150893
Incheon, 21565, South Korea
Seoul National University Hospital /ID# 150890
Seoul, 03080, South Korea
Samsung Medical Center /ID# 150892
Seoul, 06351, South Korea
The Catholic University of Korea, Seoul St. Mary's Hospital /ID# 150895
Seoul, 06591, South Korea
Hospital Duran i Reynals /ID# 148989
L'Hospitalet de Llobregat, Barcelona, 08907, Spain
Hospital Universitario de la Princesa /ID# 148980
Madrid, 28006, Spain
Hospital Universitario 12 de Octubre /ID# 148981
Madrid, 28041, Spain
Hospital Universitario Dr. Peset /ID# 148986
Valencia, 46017, Spain
Changhua Christian Hospital /ID# 154447
Changhua City, Changhua County, 50006, Taiwan
China Medical University Hospital /ID# 154446
Taichung, 40447, Taiwan
National Taiwan University Hospital /ID# 154444
Taipei, 100, Taiwan
Taipei Veterans General Hosp /ID# 154445
Taipei, 11217, Taiwan
Communal Nonprofit Enterprise Cherkasy Regional Oncology Dispensary /ID# 152414
Cherkasy, 18009, Ukraine
Municipal Non-Profit Enterprise City Clinical Hospital 4 of Dnipro City Council /ID# 152411
Dnipro, 49102, Ukraine
National Cancer Institute /ID# 152413
Kyiv, 03022, Ukraine
Leicester Royal Infirmary /ID# 149057
Leicester, England, LE1 5WW, United Kingdom
Barts Health NHS Trust /ID# 149050
London, London, City of, E1 2ES, United Kingdom
Nottingham University Hospitals NHS Trust /ID# 149047
Nottingham, Nottinghamshire, NG5 1PB, United Kingdom
Blackpool Teaching Hospitals NHS Foundation Trust /ID# 149058
Blackpool, FY3 8NR, United Kingdom
East Kent Hospitals University NHS Foundation Trust /ID# 149059
Canterbury, CT1 3NG, United Kingdom
University College London Hospitals NHS Foundation Trust /ID# 149044
London, NW1 2PG, United Kingdom
King's College Hospital NHS Foundation Trust /ID# 149045
London, SE5 9RS, United Kingdom
Manchester University NHS Foundation Trust /ID# 149046
Manchester, M13 9WL, United Kingdom
Barking, Havering and Redbridge University Hospitals NHS Trust /ID# 149055
Romford, RM7 0AG, United Kingdom
The Royal Wolverhampton NHS Trust /ID# 149043
Wolverhampton, WV10 0QP, United Kingdom
Related Publications (2)
Kumar SK, Harrison SJ, Cavo M, de la Rubia J, Popat R, Gasparetto C, Hungria V, Salwender H, Suzuki K, Kim I, Onishi M, Ku G, Pothacamury R, Jalaluddin M, Zeng J, Ross JA, Dobkowska E, Moreau P. Venetoclax or placebo in combination with bortezomib and dexamethasone in relapsed or refractory multiple myeloma (BELLINI): final overall survival results from a randomised, phase 3 study. Lancet Haematol. 2025 Aug;12(8):e574-e587. doi: 10.1016/S2352-3026(25)00139-5. Epub 2025 Jun 27.
PMID: 40587991DERIVEDKumar SK, Harrison SJ, Cavo M, de la Rubia J, Popat R, Gasparetto C, Hungria V, Salwender H, Suzuki K, Kim I, Punnoose EA, Hong WJ, Freise KJ, Yang X, Sood A, Jalaluddin M, Ross JA, Ward JE, Maciag PC, Moreau P. Venetoclax or placebo in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (BELLINI): a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2020 Dec;21(12):1630-1642. doi: 10.1016/S1470-2045(20)30525-8. Epub 2020 Oct 29.
PMID: 33129376DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Medical Services
- Organization
- AbbVie
Study Officials
- STUDY DIRECTOR
ABBVIE INC.
AbbVie
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
April 20, 2016
First Posted
April 29, 2016
Study Start
July 11, 2016
Primary Completion
March 15, 2021
Study Completion
August 15, 2022
Last Updated
August 22, 2023
Results First Posted
August 22, 2023
Record last verified: 2023-08
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
- Access Criteria
- Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.