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

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.

Study Overview

• Status: Completed
• Conditions: Relapsed/Refractory Multiple Myeloma
• Intervention / Treatment: Drug: Venetoclax; Drug: Bortezomib; Drug: Dexamethasone; Drug: Placebo for venetoclax

• Study Type: Interventional
• Enrollment (Actual): 291
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital /ID# 149108
    • Concord, New South Wales, Australia, 2139
      • Concord Repatriation General Hospital /ID# 149106
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital /ID# 149110
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital /ID# 149105
  • South Australia
    • Woodville South, South Australia, Australia, 5011
      • The Queen Elizabeth Hospital /ID# 149104
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Royal Hobart Hospital /ID# 149111
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital /ID# 149112
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Ctr /ID# 149107
    • Melbourne, Victoria, Australia, 3004
      • Alfred Health /ID# 150085
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital /ID# 148967
    • Nedlands, Western Australia, Australia, 6009
      • Perth Blood Institute Ltd /ID# 148966
• Brazil
  • Rio de Janeiro, Brazil, 20231-050
    • Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA) /ID# 149020
  • Sao Paulo, Brazil, 05403-000
    • Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo /ID# 149025
  • Goias
    • Goiania, Goias, Brazil, 74605-020
      • Hospital das Clinicas da Universidade Federal de Goiás /ID# 149290
  • Rio Grande Do Norte
    • Natal, Rio Grande Do Norte, Brazil, 59075-740
      • Liga Norte Riograndense Contra o Câncer /ID# 149023
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000
      • Hospital Sao Lucas da PUCRS /ID# 149027
  • Sao Paulo
    • São Paulo, Sao Paulo, Brazil, 04537-080
      • Clinica Sao Germano /ID# 149851
• Canada
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • Victoria Hospital /ID# 149846
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • CISSS de la Monteregie /ID# 149844
• France
  • Brest, France, 29200
    • CHRU de Brest - Hopital Morvan /ID# 149299
  • La Tronche, France, 38700
    • CHU Grenoble - Hopital Michallon /ID# 149301
  • Franche-Comte
    • Limoges CEDEX 1, Franche-Comte, France, 87042
      • CHU Limoges - Dupuytren 1 /ID# 149292
  • Pays-de-la-Loire
    • Nantes, Pays-de-la-Loire, France, 44000
      • CHU de Nantes, Hotel Dieu -HME /ID# 149294
  • Rhone
    • Pierre Benite CEDEX, Rhone, France, 69495
      • Duplicate_Centre Hospitalier Lyon Sud /ID# 149300
• Germany
  • Berlin, Germany, 10117
    • Charite Universitaetsmedizin Berlin - Campus Mitte /ID# 148949
  • Dresden, Germany, 01307
    • Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 148948
  • Hamburg, Germany, 22763
    • Asklepios Klinik Altona /ID# 150116
• Hungary
  • Budapest, Hungary, 1085
    • Semmelweis Egyetem /ID# 152519
  • Budapest, Hungary, 1085
    • Semmelweis Egyetem /ID# 152520
  • Budapest, Hungary, 1097
    • Del-pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet /ID# 152518
  • Hajdu-Bihar
    • Debrecen, Hajdu-Bihar, Hungary, 4032
      • Debreceni Egyetem Klinikai Kozpont /ID# 152517
  • Somogy
    • Kaposvár, Somogy, Hungary, 7400
      • Somogy Megyei Kaposi Mor Oktato Korhaz /ID# 152516
• Ireland
  • Galway, Ireland, H91 YR71
    • University Hospital Galway /ID# 149061
• Italy
  • Ancona, Italy, 60126
    • Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona /ID# 148942
  • Bologna, Italy, 40138
    • IRCCS Azienda Ospedaliero-Universitaria di Bologna /ID# 148936
  • Rome, Italy, 00144
    • Ospedale S.Eugenio /ID# 148938
  • Turin, Italy, 10126
    • A.O.U. Città della Salute e della Scienza di Torino/Ospedale Molinette /ID# 148943
  • Lazio
    • Rome, Lazio, Italy, 00161
      • Azienda Ospedaliero-Universitaria Policlinico Umberto I /ID# 148939
• Japan
  • Aichi
    • Nagoya shi, Aichi, Japan, 467-8602
      • Nagoya City University Hospital /ID# 150943
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan, 812-8582
      • Kyushu University Hospital /ID# 150896
  • Gifu
    • Ogaki-shi, Gifu, Japan, 503-8502
      • Ogaki Municipal Hospital /ID# 150783
  • Gunma
    • Maebashi-shi, Gunma, Japan, 371-8511
      • Gunma University Hospital /ID# 150275
    • Shibukawa-shi, Gunma, Japan, 377-0280
      • National Hospital Organization Shibukawa Medical Center /ID# 150281
  • Hiroshima
    • Hiroshima-shi, Hiroshima, Japan, 730-8619
      • Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital /ID# 150242
  • Hyogo
    • Kobe-shi, Hyogo, Japan, 650-0047
      • Kobe City Medical Center General Hospital /ID# 150944
  • Ibaraki
    • Higashi Ibaraki-gun, Ibaraki, Japan, 311-3193
      • National Hospital Organization Mito Medical Center /ID# 151051
  • Kyoto
    • Kyoto-shi, Kyoto, Japan, 602-8566
      • Duplicate_Kyoto Prefectural University of Medicine /ID# 150719
    • Kyoto-shi, Kyoto, Japan, 603-8151
      • JCHO Kyoto Kuramaguchi Medical /ID# 150781
  • Miyagi
    • Sendai-shi, Miyagi, Japan, 9808574
      • Tohoku University Hospital /ID# 150945
  • Okayama
    • Okayama-shi, Okayama, Japan, 701-1192
      • Okayama Medical Center /ID# 150717
  • Osaka
    • Osaka-shi, Osaka, Japan, 543-8555
      • Japanese Red Cross Osaka Hospital /ID# 150716
  • Saitama
    • Kawagoe-shi, Saitama, Japan, 350-8550
      • Saitama Medical Center /ID# 151044
  • Tochigi
    • Utsunomiya-shi, Tochigi, Japan, 320-0834
      • Tochigi Cancer Center /ID# 150192
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital /ID# 151039
    • Koto-ku, Tokyo, Japan, 135-8550
      • The Cancer Institute Hospital Of JFCR /ID# 150780
    • Shibuya-ku, Tokyo, Japan, 150-8935
      • Japanese Red Cross Medical Center /ID# 149902
    • Tachikawa-shi, Tokyo, Japan, 190-0014
      • National Hospital Organization Disaster Medical Center /ID# 150784
• Korea, Republic of
  • Gwangju, Korea, Republic of, 61469
    • Chonnam National University Hospital /ID# 150894
  • Incheon, Korea, Republic of, 21565
    • Gachon University Gil Medical Center /ID# 150893
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital /ID# 150890
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center /ID# 150892
  • Seoul, Korea, Republic of, 06591
    • The Catholic University of Korea, Seoul St. Mary's Hospital /ID# 150895
  • Gyeonggido
    • Goyang, Gyeonggido, Korea, Republic of, 10408
      • National Cancer Center /ID# 150889
    • Seongnam, Gyeonggido, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital /ID# 150888
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 03722
      • Duplicate_Yonsei University Health System, Severance hospital. /ID# 150891
• Russian Federation
  • Moscow, Russian Federation, 129128
    • Central Clinical Hospital RZHD Medicine /ID# 148954
  • Omsk, Russian Federation, 644013
    • Clinical Oncology Dispensary of Omsk /ID# 148953
  • Samara, Russian Federation, 443099
    • Samara State Medical University /ID# 148952
  • Ufa, Russian Federation, 450008
    • Bashkir State Medical University /ID# 151206
  • Kemerovskaya Oblast
    • Kemerovo, Kemerovskaya Oblast, Russian Federation, 650099
      • Kuzbass Regional Clinical Hospital /ID# 148955
  • Ryazanskaya Oblast
    • Ryazan, Ryazanskaya Oblast, Russian Federation, 390039
      • State Institution of Health of the Ryazan Regional Clinical Hospital /ID# 148956
  • Stavropol Skiy Kray
    • Pyatigorsk, Stavropol Skiy Kray, Russian Federation, 357500
      • LLC Novaya Klinika /ID# 148974
• Spain
  • Madrid, Spain, 28006
    • Hospital Universitario de la Princesa /ID# 148980
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre /ID# 148981
  • Valencia, Spain, 46017
    • Hospital Universitario Dr. Peset /ID# 148986
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Duran i Reynals /ID# 148989
• Taiwan
  • Changhua City, Changhua County, Taiwan, 50006
    • Changhua Christian Hospital /ID# 154447
  • Taichung City, Taiwan, 40447
    • China Medical University Hospital /ID# 154446
  • Taipei City, Taiwan, 100
    • National Taiwan University Hospital /ID# 154444
  • Taipei City, Taiwan, 11217
    • Taipei Veterans General Hosp /ID# 154445
• Ukraine
  • Cherkasy, Ukraine, 18009
    • Communal Nonprofit Enterprise Cherkasy Regional Oncology Dispensary /ID# 152414
  • Dnipro, Ukraine, 49102
    • Municipal Non-Profit Enterprise City Clinical Hospital 4 of Dnipro City Council /ID# 152411
  • Kyiv, Ukraine, 03022
    • National Cancer Institute /ID# 152413
• United Kingdom
  • Blackpool, United Kingdom, FY3 8NR
    • Blackpool Teaching Hospitals NHS Foundation Trust /ID# 149058
  • Canterbury, United Kingdom, CT1 3NG
    • East Kent Hospitals University NHS Foundation Trust /ID# 149059
  • London, United Kingdom, NW1 2PG
    • University College London Hospitals NHS Foundation Trust /ID# 149044
  • London, United Kingdom, SE5 9RS
    • King's College Hospital NHS Foundation Trust /ID# 149045
  • Manchester, United Kingdom, M13 9WL
    • Manchester University NHS Foundation Trust /ID# 149046
  • Romford, United Kingdom, RM7 0AG
    • Barking, Havering and Redbridge University Hospitals NHS Trust /ID# 149055
  • Wolverhampton, United Kingdom, WV10 0QP
    • The Royal Wolverhampton NHS Trust /ID# 149043
  • England
    • Leicester, England, United Kingdom, LE1 5WW
      • Leicester Royal Infirmary /ID# 149057
  • London, City Of
    • London, London, City Of, United Kingdom, E1 2ES
      • Barts Health NHS Trust /ID# 149050
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
      • Nottingham University Hospitals NHS Trust /ID# 149047
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Rocky Mountain Regional VA Medical Center/Eastern Colorado Health Care System /ID# 156524
    • Aurora, Colorado, United States, 80045
      • Univ of Colorado Cancer Center /ID# 149130
  • North Carolina
    • Durham, North Carolina, United States, 27710-3000
      • Duke Cancer Center /ID# 149099
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center Research /ID# 149098

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Venetoclax + Bortezomib and Dexamethasone; Cycles 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	Drug: Venetoclax; 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.; Other Names: VENCLEXTA; VENCLYXTO; Drug: Bortezomib; 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.; Other Names: Velcade; Drug: Dexamethasone; 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).
Placebo Comparator: Placebo + Bortezomib and Dexamethasone; Cycles 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	Drug: Bortezomib; 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.; Other Names: Velcade; Drug: Dexamethasone; 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).; Drug: Placebo for venetoclax; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Very Good Partial Response (VGPR) or Better Response Rate	The percentage of participants with documented best overall response of Very Good Partial Response (VGPR) or better (VGPR, Complete response [CR], or Stringent complete response [sCR]) per 2016 standard International Myeloma Working Group (IMWG) criteria as determined by an Independent Review Committee (IRC) was computed.	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	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) per investigator assessment or death due to any cause, whichever occurs first. PFS was analyzed by Kaplan-Meier methodology. BCL-2 expression was determined through central laboratory testing by immunohistochemistry (IHC) and based on a pre-specified scoring algorithm. High clinical score of 2+: ≥50% of tumor cells with moderate or higher cytoplasmic staining but < 50% of tumor cells with strong staining intensity; high clinical score of 3+: ≥50% of tumor cells with strong cytoplasmic staining.	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)	DOR is defined as the number of days from the participant's date of first documented response (partial response [PR] or better) to the date of first documented progressive disease (PD) as determined by an Independent Review Committee (IRC) or death due to multiple myeloma, whichever occurs first. DOR was analyzed by Kaplan-Meier methodology.	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	The BPI-SF is a pain-specific measure developed to assess patient-reported severity (or intensity) of pain (4 items) and the impact of pain on daily functioning (7 items) in patients with cancer pain. The four pain severity items assess pain at its "worst in last 24 hours," "least in last 24 hours," "average," and "now" (current pain). For these items, participants are asked to rate their pain on an 11-point numeric rating scale with anchors of 0 (no pain) and 10 (pain as bad as you can imagine). The Worst Pain scores range from 0 to 10, with higher scores indicating severe pain. Negative changes from baseline indicate improvement.	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)	The QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including five functional scales (physical, role, emotional, social, and cognitive), three symptom scales (fatigue, nausea and vomiting, and pain), a global health status/quality of life scale, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). For the Physical Functioning scale, participants rate five items on a four-point scale, with 1 as "not at all" and 4 as "very much." The Physical Functioning Scale scores range from 0 to 100 and were calculated per the EORTC QLQ-C30 Scoring Manual (3rd edition), version 3.0. A high scale score represents high/healthy level of functioning. Positive changes from baseline indicate improvement.	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 Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)	The QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including five functional scales (physical, role, emotional, social, and cognitive), three symptom scales (fatigue, nausea and vomiting, and pain), a global health status/quality of life scale, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). For the Global Health Status/Quality of Life scale, participants rate two items on a seven point scale, with 1 as "very poor" and 7 as "excellent." The Global Health Status/Quality of Life scale ranges from 0 to 100 and was calculated per the EORTC QLQ-C30 Scoring Manual (3rd edition), version 3.0. A high score for the global health status/QoL represents a high QoL. Positive changes from baseline indicate improvement.	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 Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score	PROMIS Cancer Fatigue SF is a seven item questionnaire that assesses the impact and experience of fatigue over the past 7 days. All questions employ the following five response options: 1 = Not at all, 2 = A little bit, 3 = Somewhat, 4 = Quite a bit, and 5 = Very much. The total raw score is the sum of the responses to each question and is converted to a T-score. The T-score re-scales the total raw score to a standardized score with a mean of 50 and a standard deviation of 10. The [PROMIS] Cancer Fatigue Short Form [SF] 7a T-Scores range from 29.4 to 83.2, with higher scores indicating more fatigue. Negative changes from baseline indicate improvement.	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
Overall Survival (OS).	OS is defined as the number of days from the date of randomization to the date of death due to any cause. All events of death were to be included, regardless of whether the event occurred while the participant was still taking study drug or after the participant discontinued study drug. If a participant is not known to have died, OS was censored at the date of last contact. The distribution of OS was estimated using Kaplan-Meier methodology.	Median duration of follow-up was 45.6 months for the venetoclax group and 45.6 months for the placebo group
Time to Progression (TTP)	TTP is defined as the number of days from the date of randomization to the date of first documented progressive disease (PD) as determined by an Independent Review Committee (IRC) or death due to multiple myeloma, whichever occurs first. TTP was analyzed by Kaplan-Meier methodology.	Median time on follow-up up was 28.6 months for the venetoclax group and 28.6 months for the placebo group
Overall Response Rate (ORR)	Overall response rate is defined as the percentage of participants with documented best overall response of Partial Response (PR) or better (PR, Very good partial response [VGPR], Complete response [CR], or Stringent complete response [sCR]) per International Myeloma Working Group (IMWG) criteria as determined by an Independent Review Committee (IRC).	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
Minimal Residual Disease (MRD) Negativity Rate	MRD negativity rate is defined as the percentage of participants who have negative MRD by bone marrow aspirate at any time point after randomization and before progression or starting subsequent therapy. MRD negativity was defined at 10^-5 threshold (less than one residual myeloma cell per 10^5 total nucleated cells) as measured by centralized testing of bone marrow aspirate by Next Generation Sequencing (NGS). MRD positive participants include those of which all tested samples were found to be MRD positive or indeterminate. Participants with missing or unevaluable MRD status were considered as MRD positive.	Assessed at Screening; to confirm a stringent Complete Response (sCR) or Complete Response (CR); at 6 months and 12 months post-confirmed CR/sCR

Collaborators and Investigators

• Sponsor: AbbVie
• Collaborators: Genentech, Inc.
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

General Publications

• Kumar 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2016
• Primary Completion (Actual): March 15, 2021
• Study Completion (Actual): August 15, 2022

Study Registration Dates

• First Submitted: April 20, 2016
• First Submitted That Met QC Criteria: April 27, 2016
• First Posted (Estimated): April 29, 2016

Study Record Updates

• Last Update Posted (Actual): August 22, 2023
• Last Update Submitted That Met QC Criteria: August 18, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Multiple myeloma; Relapsed multiple myeloma; Refractory multiple myeloma; Relapsed/refractory multiple myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone; Venetoclax; Bortezomib
• Other Study ID Numbers: M14-031; 2015-004411-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• IPD Sharing 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/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No