A Study Evaluating Venetoclax (ABT-199) in Multiple Myeloma Subjects Who Are Receiving Bortezomib and Dexamethasone as Standard Therapy

NCT ID: NCT02755597

Last Updated: 2023-08-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 291 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-11
• Study Completion Date: 2022-08-15

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.

Conditions

Relapsed/Refractory Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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 + 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

Group Type: PLACEBO_COMPARATOR

Bortezomib

Intervention Type: DRUG

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

Intervention Type: DRUG

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 for venetoclax

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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).

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

VENCLEXTA; VENCLYXTO; Velcade

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

ABBVIE INC.

Role: STUDY_DIRECTOR

AbbVie

Locations

Rocky Mountain Regional VA Medical Center/Eastern Colorado Health Care System /ID# 156524

Aurora, Colorado, United States

Univ of Colorado Cancer Center /ID# 149130

Aurora, Colorado, United States

Duke Cancer Center /ID# 149099

Durham, North Carolina, United States

Gabrail Cancer Center Research /ID# 149098

Canton, Ohio, United States

Royal Prince Alfred Hospital /ID# 149108

Camperdown, New South Wales, Australia

Concord Repatriation General Hospital /ID# 149106

Concord, New South Wales, Australia

Liverpool Hospital /ID# 149110

Liverpool, New South Wales, Australia

Royal Brisbane and Women's Hospital /ID# 149105

Herston, Queensland, Australia

The Queen Elizabeth Hospital /ID# 149104

Woodville South, South Australia, Australia

Royal Hobart Hospital /ID# 149111

Hobart, Tasmania, Australia

Box Hill Hospital /ID# 149112

Box Hill, Victoria, Australia

Peter MacCallum Cancer Ctr /ID# 149107

Melbourne, Victoria, Australia

Alfred Health /ID# 150085

Melbourne, Victoria, Australia

Fiona Stanley Hospital /ID# 148967

Murdoch, Western Australia, Australia

Perth Blood Institute Ltd /ID# 148966

Nedlands, Western Australia, Australia

Hospital das Clinicas da Universidade Federal de Goiás /ID# 149290

Goiânia, Goiás, Brazil

Liga Norte Riograndense Contra o Câncer /ID# 149023

Natal, Rio Grande do Norte, Brazil

Hospital Sao Lucas da PUCRS /ID# 149027

Porto Alegre, Rio Grande do Sul, Brazil

Clinica Sao Germano /ID# 149851

São Paulo, São Paulo, Brazil

Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA) /ID# 149020

Rio de Janeiro, , Brazil

Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo /ID# 149025

São Paulo, , Brazil

Victoria Hospital /ID# 149846

London, Ontario, Canada

CISSS de la Monteregie /ID# 149844

Greenfield Park, Quebec, Canada

CHU Limoges - Dupuytren 1 /ID# 149292

Limoges, Franche-Comte, France

CHU de Nantes, Hotel Dieu -HME /ID# 149294

Nantes, Pays de la Loire Region, France

Duplicate_Centre Hospitalier Lyon Sud /ID# 149300

Pierre-Bénite, Rhone, France

CHRU de Brest - Hopital Morvan /ID# 149299

Brest, , France

CHU Grenoble - Hopital Michallon /ID# 149301

La Tronche, , France

Charite Universitaetsmedizin Berlin - Campus Mitte /ID# 148949

Berlin, , Germany

Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 148948

Dresden, , Germany

Asklepios Klinik Altona /ID# 150116

Hamburg, , Germany

Debreceni Egyetem Klinikai Kozpont /ID# 152517

Debrecen, Hajdú-Bihar, Hungary

Somogy Megyei Kaposi Mor Oktato Korhaz /ID# 152516

Kaposvár, Somogy County, Hungary

Semmelweis Egyetem /ID# 152519

Budapest, , Hungary

Semmelweis Egyetem /ID# 152520

Budapest, , Hungary

Del-pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet /ID# 152518

Budapest, , Hungary

University Hospital Galway /ID# 149061

Galway, , Ireland

Azienda Ospedaliero-Universitaria Policlinico Umberto I /ID# 148939

Rome, Lazio, Italy

Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona /ID# 148942

Ancona, , Italy

IRCCS Azienda Ospedaliero-Universitaria di Bologna /ID# 148936

Bologna, , Italy

Ospedale S.Eugenio /ID# 148938

Rome, , Italy

A.O.U. Città della Salute e della Scienza di Torino/Ospedale Molinette /ID# 148943

Turin, , Italy

Nagoya City University Hospital /ID# 150943

Nagoya, Aichi-ken, Japan

Kyushu University Hospital /ID# 150896

Fukuoka, Fukuoka, Japan

Ogaki Municipal Hospital /ID# 150783

Ogaki-shi, Gifu, Japan

Gunma University Hospital /ID# 150275

Maebashi, Gunma, Japan

National Hospital Organization Shibukawa Medical Center /ID# 150281

Shibukawa-shi, Gunma, Japan

Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital /ID# 150242

Hiroshima, Hiroshima, Japan

Kobe City Medical Center General Hospital /ID# 150944

Kobe, Hyōgo, Japan

National Hospital Organization Mito Medical Center /ID# 151051

Higashi Ibaraki-gun, Ibaraki, Japan

Duplicate_Kyoto Prefectural University of Medicine /ID# 150719

Kyoto, Kyoto, Japan

JCHO Kyoto Kuramaguchi Medical /ID# 150781

Kyoto, Kyoto, Japan

Tohoku University Hospital /ID# 150945

Sendai, Miyagi, Japan

Okayama Medical Center /ID# 150717

Okayama, Okayama-ken, Japan

Japanese Red Cross Osaka Hospital /ID# 150716

Osaka, Osaka, Japan

Saitama Medical Center /ID# 151044

Kawagoe-shi, Saitama, Japan

Tochigi Cancer Center /ID# 150192

Utsunomiya, Tochigi, Japan

National Cancer Center Hospital /ID# 151039

Chuo-ku, Tokyo, Japan

The Cancer Institute Hospital Of JFCR /ID# 150780

Koto-ku, Tokyo, Japan

Japanese Red Cross Medical Center /ID# 149902

Shibuya-ku, Tokyo, Japan

National Hospital Organization Disaster Medical Center /ID# 150784

Tachikawa-shi, Tokyo, Japan

Kuzbass Regional Clinical Hospital /ID# 148955

Kemerovo, Kemerovo Oblast, Russia

State Institution of Health of the Ryazan Regional Clinical Hospital /ID# 148956

Ryazan, Ryazan Oblast, Russia

LLC Novaya Klinika /ID# 148974

Pyatigorsk, Stavropol Kray, Russia

Central Clinical Hospital RZHD Medicine /ID# 148954

Moscow, , Russia

Clinical Oncology Dispensary of Omsk /ID# 148953

Omsk, , Russia

Samara State Medical University /ID# 148952

Samara, , Russia

Bashkir State Medical University /ID# 151206

Ufa, , Russia

National Cancer Center /ID# 150889

Goyang, Gyeonggido, South Korea

Seoul National University Bundang Hospital /ID# 150888

Seongnam, Gyeonggido, South Korea

Duplicate_Yonsei University Health System, Severance hospital. /ID# 150891

Seoul, Seoul Teugbyeolsi, South Korea

Chonnam National University Hospital /ID# 150894

Gwangju, , South Korea

Gachon University Gil Medical Center /ID# 150893

Incheon, , South Korea

Seoul National University Hospital /ID# 150890

Seoul, , South Korea

Samsung Medical Center /ID# 150892

Seoul, , South Korea

The Catholic University of Korea, Seoul St. Mary's Hospital /ID# 150895

Seoul, , South Korea

Hospital Duran i Reynals /ID# 148989

L'Hospitalet de Llobregat, Barcelona, Spain

Hospital Universitario de la Princesa /ID# 148980

Madrid, , Spain

Hospital Universitario 12 de Octubre /ID# 148981

Madrid, , Spain

Hospital Universitario Dr. Peset /ID# 148986

Valencia, , Spain

Changhua Christian Hospital /ID# 154447

Changhua City, Changhua County, , Taiwan

China Medical University Hospital /ID# 154446

Taichung, , Taiwan

National Taiwan University Hospital /ID# 154444

Taipei, , Taiwan

Taipei Veterans General Hosp /ID# 154445

Taipei, , Taiwan

Communal Nonprofit Enterprise Cherkasy Regional Oncology Dispensary /ID# 152414

Cherkasy, , Ukraine

Municipal Non-Profit Enterprise City Clinical Hospital 4 of Dnipro City Council /ID# 152411

Dnipro, , Ukraine

National Cancer Institute /ID# 152413

Kyiv, , Ukraine

Leicester Royal Infirmary /ID# 149057

Leicester, England, United Kingdom

Barts Health NHS Trust /ID# 149050

London, London, City of, United Kingdom

Nottingham University Hospitals NHS Trust /ID# 149047

Nottingham, Nottinghamshire, United Kingdom

Blackpool Teaching Hospitals NHS Foundation Trust /ID# 149058

Blackpool, , United Kingdom

East Kent Hospitals University NHS Foundation Trust /ID# 149059

Canterbury, , United Kingdom

University College London Hospitals NHS Foundation Trust /ID# 149044

London, , United Kingdom

King's College Hospital NHS Foundation Trust /ID# 149045

London, , United Kingdom

Manchester University NHS Foundation Trust /ID# 149046

Manchester, , United Kingdom

Barking, Havering and Redbridge University Hospitals NHS Trust /ID# 149055

Romford, , United Kingdom

The Royal Wolverhampton NHS Trust /ID# 149043

Wolverhampton, , United Kingdom

Countries

United States; Australia; Brazil; Canada; France; Germany; Hungary; Ireland; Italy; Japan; Russia; South Korea; Spain; Taiwan; Ukraine; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 40587991 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33129376 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-004411-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M14-031

Identifier Type: -

Identifier Source: org_study_id