A Study Evaluating Venetoclax (ABT-199) in Multiple Myeloma Subjects Who Are Receiving Bortezomib and Dexamethasone as Standard Therapy (Bellini)
Relapsed/Refractory Multiple Myeloma
About this trial
This is an interventional treatment trial for Relapsed/Refractory Multiple Myeloma focused on measuring Relapsed/refractory multiple myeloma, Relapsed multiple myeloma, Refractory multiple myeloma, Multiple myeloma
Eligibility Criteria
Inclusion Criteria:
- Eastern Cooperative Oncology Group (ECOG) performance score less than or equal to 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 non responsive (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 greater than or equal to 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 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 PR, AND participant did not discontinue any proteasome inhibitor due to intolerance or greater than or equal to Grade 3 related toxicity.
- Participant has measurable disease at Screening, defined as at least one of the following: Serum M-protein greater than or equal to 0.5 g/dL, OR Urine M-protein greater than or equal to 200 mg in 24-hours, OR serum immunoglobulin free light chain (FLC) greater than or equal to 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 greater than or equal to 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 greater than or equal to Grade 3 or greater than or equal to 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).
Sites / Locations
- Rocky Mountain Regional VA Medical Center/Eastern Colorado Health Care System /ID# 156524
- Univ of Colorado Cancer Center /ID# 149130
- Duke Cancer Center /ID# 149099
- Gabrail Cancer Center Research /ID# 149098
- Royal Prince Alfred Hospital /ID# 149108
- Concord Repatriation General Hospital /ID# 149106
- Liverpool Hospital /ID# 149110
- Royal Brisbane and Women's Hospital /ID# 149105
- The Queen Elizabeth Hospital /ID# 149104
- Royal Hobart Hospital /ID# 149111
- Box Hill Hospital /ID# 149112
- Peter MacCallum Cancer Ctr /ID# 149107
- Alfred Health /ID# 150085
- Fiona Stanley Hospital /ID# 148967
- Perth Blood Institute Ltd /ID# 148966
- Hospital das Clinicas da Universidade Federal de Goiás /ID# 149290
- Liga Norte Riograndense Contra o Câncer /ID# 149023
- Hospital Sao Lucas da PUCRS /ID# 149027
- Clinica Sao Germano /ID# 149851
- Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA) /ID# 149020
- Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo /ID# 149025
- Victoria Hospital /ID# 149846
- CISSS de la Monteregie /ID# 149844
- CHU Limoges - Dupuytren 1 /ID# 149292
- CHU de Nantes, Hotel Dieu -HME /ID# 149294
- Duplicate_Centre Hospitalier Lyon Sud /ID# 149300
- CHRU de Brest - Hopital Morvan /ID# 149299
- CHU Grenoble - Hopital Michallon /ID# 149301
- Charite Universitaetsmedizin Berlin - Campus Mitte /ID# 148949
- Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 148948
- Asklepios Klinik Altona /ID# 150116
- Debreceni Egyetem Klinikai Kozpont /ID# 152517
- Somogy Megyei Kaposi Mor Oktato Korhaz /ID# 152516
- Semmelweis Egyetem /ID# 152519
- Semmelweis Egyetem /ID# 152520
- Del-pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet /ID# 152518
- University Hospital Galway /ID# 149061
- Azienda Ospedaliero-Universitaria Policlinico Umberto I /ID# 148939
- Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona /ID# 148942
- IRCCS Azienda Ospedaliero-Universitaria di Bologna /ID# 148936
- Ospedale S.Eugenio /ID# 148938
- A.O.U. Città della Salute e della Scienza di Torino/Ospedale Molinette /ID# 148943
- Nagoya City University Hospital /ID# 150943
- Kyushu University Hospital /ID# 150896
- Ogaki Municipal Hospital /ID# 150783
- Gunma University Hospital /ID# 150275
- National Hospital Organization Shibukawa Medical Center /ID# 150281
- Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital /ID# 150242
- Kobe City Medical Center General Hospital /ID# 150944
- National Hospital Organization Mito Medical Center /ID# 151051
- Duplicate_Kyoto Prefectural University of Medicine /ID# 150719
- JCHO Kyoto Kuramaguchi Medical /ID# 150781
- Tohoku University Hospital /ID# 150945
- Okayama Medical Center /ID# 150717
- Japanese Red Cross Osaka Hospital /ID# 150716
- Saitama Medical Center /ID# 151044
- Tochigi Cancer Center /ID# 150192
- National Cancer Center Hospital /ID# 151039
- The Cancer Institute Hospital Of JFCR /ID# 150780
- Japanese Red Cross Medical Center /ID# 149902
- National Hospital Organization Disaster Medical Center /ID# 150784
- National Cancer Center /ID# 150889
- Seoul National University Bundang Hospital /ID# 150888
- Duplicate_Yonsei University Health System, Severance hospital. /ID# 150891
- Chonnam National University Hospital /ID# 150894
- Gachon University Gil Medical Center /ID# 150893
- Seoul National University Hospital /ID# 150890
- Samsung Medical Center /ID# 150892
- The Catholic University of Korea, Seoul St. Mary's Hospital /ID# 150895
- Kuzbass Regional Clinical Hospital /ID# 148955
- State Institution of Health of the Ryazan Regional Clinical Hospital /ID# 148956
- LLC Novaya Klinika /ID# 148974
- Central Clinical Hospital RZHD Medicine /ID# 148954
- Clinical Oncology Dispensary of Omsk /ID# 148953
- Samara State Medical University /ID# 148952
- Bashkir State Medical University /ID# 151206
- Hospital Duran i Reynals /ID# 148989
- Hospital Universitario de la Princesa /ID# 148980
- Hospital Universitario 12 de Octubre /ID# 148981
- Hospital Universitario Dr. Peset /ID# 148986
- Changhua Christian Hospital /ID# 154447
- China Medical University Hospital /ID# 154446
- National Taiwan University Hospital /ID# 154444
- Taipei Veterans General Hosp /ID# 154445
- Communal Nonprofit Enterprise Cherkasy Regional Oncology Dispensary /ID# 152414
- Municipal Non-Profit Enterprise City Clinical Hospital 4 of Dnipro City Council /ID# 152411
- National Cancer Institute /ID# 152413
- Leicester Royal Infirmary /ID# 149057
- Barts Health NHS Trust /ID# 149050
- Nottingham University Hospitals NHS Trust /ID# 149047
- Blackpool Teaching Hospitals NHS Foundation Trust /ID# 149058
- East Kent Hospitals University NHS Foundation Trust /ID# 149059
- University College London Hospitals NHS Foundation Trust /ID# 149044
- King's College Hospital NHS Foundation Trust /ID# 149045
- Manchester University NHS Foundation Trust /ID# 149046
- Barking, Havering and Redbridge University Hospitals NHS Trust /ID# 149055
- The Royal Wolverhampton NHS Trust /ID# 149043
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Venetoclax + Bortezomib and Dexamethasone
Placebo + 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
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