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

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ClinicalTrials.gov Identifier: NCT02755597
Recruitment Status : Active, not recruiting
First Posted : April 29, 2016
Last Update Posted : April 23, 2018
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
AbbVie

Brief Summary:
This is a Phase 3, multicenter, randomized, double blind, placebo-controlled study evaluating the efficacy and safety of venetoclax plus bortezomib and dexamethasone in subjects 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.

Condition or disease Intervention/treatment Phase
Relapsed/Refractory Multiple Myeloma Drug: Placebo Drug: Bortezomib Drug: Dexamethasone Drug: Venetoclax Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 291 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : July 12, 2016
Estimated Primary Completion Date : September 2, 2019
Estimated Study Completion Date : April 14, 2020


Arm Intervention/treatment
Placebo Comparator: Placebo + Bortezomib and Dexamethasone
Cycles 1-8: Placebo (to match venetoclax 100mg tablet) 800mg orally every day (QD) on days 1 - 21 plus bortezomib 1.3mg/m2 on days 1,4,8 & 11 and dexamethasone 20 mg on Days 1, 2, 4, 5, 8, 9, 11 and 12 Cycles 9 and beyond: Placebo (to match venetoclax 100mg tablet) 800mg orally every day (QD) on days 1 - 35 plus bortezomib 1.3mg/m2 on days 1, 8, 15 and 22 and dexamethasone 20 mg on Days 1, 2, 8, 9, 15, 16, 22 and 23
Drug: Placebo
Tablet
Drug: Bortezomib
Solution for subcutaneous injection
Drug: Dexamethasone
Tablet
Experimental: Venetoclax + Bortezomib and Dexamethasone
Cycles 1-8: Venetoclax 800mg orally every day (QD) on days 1 - 21 plus bortezomib 1.3mg/m2 on days 1,4,8 & 11 and dexamethasone 20 mg on Days 1, 2, 4, 5, 8, 9, 11 and 12 Cycles 9 and beyond: Venetoclax 800mg orally every day (QD) on days 1 - 35 plus bortezomib 1.3mg/m2 on days 1, 8, 15 and 22 and dexamethasone 20 mg on Days 1, 2, 8, 9, 15, 16, 22 and 23
Drug: Bortezomib
Solution for subcutaneous injection
Drug: Dexamethasone
Tablet
Drug: Venetoclax
Tablet
Other Name: ABT-199



Primary Outcome Measures :
  1. Progression-free survival (PFS). [ Time Frame: Measured at subject's baseline (prior to subject's first dose) and at Day 1 of every Cycle thereafter for up to 3 years following the last subject first dose. ]
    Collect International Myeloma Working Group (IMWG) disease assessments at Cycle 1 Day 1 (C1D1) of each cycle or to confirm disease progression.


Secondary Outcome Measures :
  1. Brief Pain Inventory - Short Form [BPI-SF] - Worst Pain [ Time Frame: Starting with Cycle 1 (Cycles 1 - 8 are 21 days, Cycles 9 and beyond are 35 days), collect on Day 1 of every other cycle and the Treatment Completion Visit (TCV) while participant is on treatment (approximately 2 years). ]
  2. Duration of Response (DOR). [ Time Frame: Measured at subject's initial response and at Day 1 of every Cycle thereafter for up to 3 years following the last subject first dose. ]
    Collect International Myeloma Working Group (IMWG) disease assessments at C1D1 of each cycle or to confirm disease progression.

  3. Progression-Free Survival (PFS) in subjects with high B-cell lymphoma 2 (BCL-2) expression. [ Time Frame: Measured at subject's baseline (prior to subject's first dose) and at Day 1 of every Cycle thereafter for up to 3 years following the last subject first dose. ]
    Bone marrow aspirate and bone marrow core biopsy tissue will be evaluated with the goal of defining the relationship between BCL-2 expression and disease status.

  4. Minimal Residual Disease (MRD) status. [ Time Frame: Measured from baseline up to the time of suspected CR/stringent complete response (sCR) with an expected average of 6 months. ]
    MRD status will be assessed using Next Generation Sequencing.

  5. Objective Response Rate (ORR). [ Time Frame: Measured at subject's baseline (prior to subject's first dose) and at Day 1 of every Cycle thereafter for up to 3 years following the last subject first dose. ]
    Collect International Myeloma Working Group (IMWG) disease assessments at C1D1 of each cycle or to confirm disease progression.

  6. Patient Reported Outcomes Measurement Information System - (PROMIS) [ Time Frame: Starting with Cycle 1 (Cycles 1 - 8 are 21 days, Cycles 9 and beyond are 35 days), collect on Day 1 of every other cycle and the Treatment Completion Visit (TCV) while participant is on treatment (approximately 2 years). ]
  7. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) - Physical Functioning [ Time Frame: Starting with Cycle 1 (Cycles 1 - 8 are 21 days, Cycles 9 and beyond are 35 days), collect on Day 1 of every other cycle and the Treatment Completion Visit (TCV) while participant is on treatment (approximately 2 years). ]
  8. Overall survival (OS). [ Time Frame: Measured up to 6 years after the first subject is randomized. ]
    Measured from the date of the last dose and continuing either until the endpoint of death, until the subject is lost to follow-up, subject withdraws consent, or until study termination by AbbVie, whichever occurs first.

  9. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) - Global Health Status [ Time Frame: Starting with Cycle 1 (Cycles 1 - 8 are 21 days, Cycles 9 and beyond are 35 days), collect on Day 1 of every other cycle and the Treatment Completion Visit (TCV) while participant is on treatment (approximately 2 years). ]
  10. Very Good Partial Response (VGPR) or better response rate. [ Time Frame: Measured at subject's baseline (prior to subject's first dose) and at Day 1 of every Cycle thereafter for up to 3 years following the last subject first dose. ]
    Collect International Myeloma Working Group (IMWG) disease assessments at C1D1 of each cycle or to confirm disease progression.

  11. Time to disease progression (TTP). [ Time Frame: Measured at subject's baseline (prior to subject's first dose) and at Day 1 of every Cycle thereafter for up to 3 years following the last subject first dose. ]
    Collect International Myeloma Working Group (IMWG) disease assessments at C1D1 of each cycle or to confirm disease progression.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 or oligo-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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02755597


  Hide Study Locations
Locations
United States, Colorado
Univ of Colorado Cancer Center
Aurora, Colorado, United States, 80045
VA Eastern Colorado Healthcare
Denver, Colorado, United States, 80220
United States, North Carolina
Duke Univ Med Ctr
Durham, North Carolina, United States, 27710
United States, Ohio
Gabrail Cancer Center Research
Canton, Ohio, United States, 44718
Australia, New South Wales
Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia, 2050
Concord Repatriation & Gen Hos
Concord, New South Wales, Australia, 2139
Liverpool Hospital
Liverpool, New South Wales, Australia, 2170
Australia, Queensland
Royal Brisbane and Women's Hospital
Herston, Queensland, Australia, 4029
Australia, South Australia
The Queen Elizabeth Hospital
Woodville, South Australia, Australia, 5011
Australia, Tasmania
Royal Hobart Hospital
Hobart, Tasmania, Australia, 7000
Australia, Victoria
Peter MacCallum Cancer Ctr
Melbourne, Victoria, Australia, 3000
Alfred Health
Melbourne, Victoria, Australia, 3004
Box Hill Hospital
Melbourne, Victoria, Australia, 3128
Australia, Western Australia
Fiona Stanley Hospital
Murdoch, Western Australia, Australia, 6150
Perth Blood Institute Ltd
Nedlands, Western Australia, Australia, 6009
Brazil
Universidade Federal de Goias
Goiania, Goias, Brazil, 74605-020
Liga Norte Rigrandese Contra o
Natal, Rio Grande Do Norte, Brazil, 59062-000
Hospital Sao Lucas da PUCRS
Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000
Hospital das Clinicas da Faculdade de Medicina da USP - HCFMUSP
São Paulo, Sao Paulo, Brazil, 05403-000
INCA
Rio de Janeiro, Brazil, 20231-050
Clinica Sao Germano
Sao Paulo, Brazil, 04537-080
Canada, Ontario
Victoria Hospital
London, Ontario, Canada, N6A 4L6
Canada, Quebec
CISSS de la Monteregie
Greenfield Park, Quebec, Canada, J4V 2H1
France
CHU Dupuytren
Limoges CEDEX 1, Franche-Comte, France, 87042
Centre Hospitalier Lyon Sud
Pierre Benite CEDEX, Rhone, France, 69495
CHRU de Brest - Hopital Morvan
Brest, France, 29200
CHU de Grenoble - Albet Michal
Grenoble, France, 38043
CHU de Nantes, Hotel Dieu -HME
Nantes, France, 44093
Germany
Charité Universitätsmedizin Campus Mitte
Berlin, Germany, 10117
Universitaetklinikum Dresden
Dresden, Germany, 01307
Asklepios Klinik Altona
Hamburg, Germany, 22763
Hungary
Dél-pesti Centrumkórház- Országos Hematológiai és Infektológiai Intézet
Budapest IX, Budapest, Hungary, 1097
Semmelweis Egyetem
Budapest, Hungary, 1085
Debreceni Egyetem Klinikai Koz
Debrecen, Hungary, 4032
Somogy Megyei Kaposi Mor Oktat
Kaposvár, Hungary, 7400
Ireland
Galway University Hospital
Galway, Ireland, H91 YR71
Italy
A.O.U. Policlinico S.Orsola-Malpighi
Bologna, Emilia-Romagna, Italy, 40138
AP Romano Umberto I
Rome, Lazio, Italy, 00161
A.O. Univ. Ospedali Riuniti
Ancona, Marche, Italy, 60126
Ospedale S.Eugenio
Rome, Italy, 00144
Ospedale Molinette
Turin, Italy, 10126
Japan
Nagoya City University Hospital
Nagoya-shi, Aichi, Japan, 467-8602
Kyushu University Hospital
Fukuoka-shi, Fukuoka, Japan, 812-8582
Ogaki Municipal Hospital
Ogaki City, Gifu, Japan, 503-8502
Gunma University Hospital
Maebashi-shi, Gunma, Japan, 371-8511
National Hospital Organization
渋川市, Gunma, Japan, 〒377-0280
Hiroshima Red Cross Hospital
Hiroshima-shi, Hiroshima, Japan, 730-0052
Kobe City Med Ctr General Hosp
Kobe-shi, Hyogo, Japan, 650-0047
National Hospital Organization Mito Medical Center
Higashi Ibaraki-gun, Ibaraki, Japan, 3113193
Kyoto Prefect Univ Med
Kyoto-shi, Kyoto, Japan, 602-8566
JCHO Kyoto Kuramaguchi Medical
Kyoto-shi, Kyoto, Japan, 603-8151
Tohoku University Hospital
Sendai-shi, Miyagi, Japan, 980-8574
Okayama Medical Center
岡山市, Okayama, Japan, 〒701-1192
Japanese Red Cross Osaka Hospi
Osaka-shi, Osaka, Japan, 543-8555
Saitama Medical Center
Kawagoe-shi, Saitama, Japan, 350-8550
Tochigi Cancer Center
Utsunomiya-shi, Tochigi, Japan, 320-0834
National Cancer Center Hosp
Chuo-ku, Tokyo, Japan, 104-0045
The Cancer Institute Hosp JFCR
Koto-ku, Tokyo, Japan, 135-8550
Japanese Red Cross Med Ctr
Shibuya-ku, Tokyo, Japan, 150-0002
National Hospital Organization Disaster Medical Center
立川市, Tokyo, Japan, 〒190-0014
Korea, Republic of
National Cancer Center
Goyang, Gyeonggido, Korea, Republic of, 10408
Seoul National Univ Bundang ho
Seongnam, Gyeonggido, Korea, Republic of, 13620
Gachon University Gill Hosp
Incheon, Incheon Gwang Yeogsi, Korea, Republic of, 21565
Chonnam National University Hospital
Gwangju, Jeonranamdo, Korea, Republic of, 61469
Samsung Medical Center
Gangnam-gu, Seoul Teugbyeolsi, Korea, Republic of, 06351
Seoul National University Hospital
Jongno-gu, Seoul Teugbyeolsi, Korea, Republic of, 03080
Severance Hospital
Seoul, Seoul Teugbyeolsi, Korea, Republic of, 03722
Cath Univ Seoul St Mary's Hosp
Seoul, Seoul Teugbyeolsi, Korea, Republic of, 06591
Russian Federation
State Institution of Health of the "Ryazan Regional Clinical Hospital"
Ryazan, Ryazanskaya Oblast, Russian Federation, 390039
Kemerovo Regional Hospital
Kemerovo, Russian Federation, 650000
Central Clinical Hosp 2
Moscow, Russian Federation, 129128
Clinical Onco Dispensary
Omsk, Russian Federation, 644013
LLC Novaya Klinika
Pyatigorsk, Russian Federation, 357532
Samara State Medical Universit
Samara, Russian Federation, 443099
Medical Clinica of Bashkir
UFA, Russian Federation, 450000
Spain
Hospital Duran i Reynals
L'Hospitalet de Llobregat, Barcelona, Spain, 08907
Hospital Univ de la Princesa
Madrid, Spain, 28006
Hosp Univ 12 de Octubre
Madrid, Spain, 28041
Hospital Univ Dr. Peset
Valencia, Spain, 46017
Taiwan
China Medical University Hosp
Taichung City, Taichung, Taiwan, 40447
National Taiwan Univ Hosp
Taipei City, Taipei, Taiwan, 10002
Changhua Christian Hospital
Changhua County, Taiwan, 50006
Taipei Veterans General Hosp
Taipei City, Taiwan, 11217
Ukraine
Cherkassy Regional Onc Ctr
Cherkasy, Ukraine, 18000
City Multi-Field Clin Hosp #4
Dnipropetrovsk, Ukraine, 49102
National Cancer Institute
Kiev, Ukraine, 03022
United Kingdom
Leicester Royal Infirmary
Leicester, England, United Kingdom, LE1 5WW
Blackpool Teaching Hosp NHS
Blackpool, United Kingdom, FY3 8NR
East Kent Hosp Univ NHS Trust
Canterbury, United Kingdom, CT1 3NG
St Bartholomew's Hospital, Bar
London, United Kingdom, EC1A 7BE
University College Hospitals
London, United Kingdom, NW1 2BU
King's College Hospital NHS
London, United Kingdom, SE5 9RS
Manchester Royal Infirmary, Ma
Manchester, United Kingdom, M13 9WL
Nottingham Univ Hospitals NHS
Nottingham, United Kingdom, NG5 1PB
Queens Hospital
Romford, United Kingdom, RM7 0AG
The Royal Wolverhampton NHS Tr
Wolverhampton, United Kingdom, WV10 0QP
Sponsors and Collaborators
AbbVie
Genentech, Inc.
Investigators
Study Director: AbbVie Inc. AbbVie

Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT02755597     History of Changes
Other Study ID Numbers: M14-031
2015-004411-20 ( EudraCT Number )
First Posted: April 29, 2016    Key Record Dates
Last Update Posted: April 23, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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

Keywords provided by AbbVie:
relapsed/refractory multiple myeloma
relapsed multiple myeloma
refractory multiple myeloma
multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Venetoclax
Bortezomib
BB 1101
Proteasome Inhibitors
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal