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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02755597




Registration number
NCT02755597
Ethics application status
Date submitted
20/04/2016
Date registered
29/04/2016

Titles & IDs
Public title
A Study Evaluating Venetoclax (ABT-199) in Multiple Myeloma Subjects Who Are Receiving Bortezomib and Dexamethasone as Standard Therapy
Scientific 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
Secondary ID [1] 0 0
2015-004411-20
Secondary ID [2] 0 0
M14-031
Universal Trial Number (UTN)
Trial acronym
Bellini
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed/Refractory Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Venetoclax
Treatment: Drugs - Bortezomib
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Placebo for venetoclax

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

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


Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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).

Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS)
Timepoint [1] 0 0
Median duration of follow-up was 28.6 months for the venetoclax group and 28.6 months for the placebo group
Secondary outcome [1] 0 0
Very Good Partial Response (VGPR) or Better Response Rate
Timepoint [1] 0 0
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
Secondary outcome [2] 0 0
Progression-Free Survival (PFS) in Participants With High B-cell Lymphoma 2 (BCL-2) Expression
Timepoint [2] 0 0
Median duration of follow-up was 28.6 months for the venetoclax group and 28.6 months for the placebo group
Secondary outcome [3] 0 0
Duration of Response (DOR)
Timepoint [3] 0 0
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
Secondary outcome [4] 0 0
Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain
Timepoint [4] 0 0
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
Secondary outcome [5] 0 0
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)
Timepoint [5] 0 0
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
Secondary outcome [6] 0 0
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)
Timepoint [6] 0 0
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
Secondary outcome [7] 0 0
Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score
Timepoint [7] 0 0
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
Secondary outcome [8] 0 0
Overall Survival (OS).
Timepoint [8] 0 0
Median duration of follow-up was 45.6 months for the venetoclax group and 45.6 months for the placebo group
Secondary outcome [9] 0 0
Time to Progression (TTP)
Timepoint [9] 0 0
Median time on follow-up up was 28.6 months for the venetoclax group and 28.6 months for the placebo group
Secondary outcome [10] 0 0
Overall Response Rate (ORR)
Timepoint [10] 0 0
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
Secondary outcome [11] 0 0
Minimal Residual Disease (MRD) Negativity Rate
Timepoint [11] 0 0
Assessed at Screening; to confirm a stringent Complete Response (sCR) or Complete Response (CR); at 6 months and 12 months post-confirmed CR/sCR

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
99 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital /ID# 149108 - Camperdown
Recruitment hospital [2] 0 0
Concord Repatriation General Hospital /ID# 149106 - Concord
Recruitment hospital [3] 0 0
Liverpool Hospital /ID# 149110 - Liverpool
Recruitment hospital [4] 0 0
Royal Brisbane and Women's Hospital /ID# 149105 - Herston
Recruitment hospital [5] 0 0
The Queen Elizabeth Hospital /ID# 149104 - Woodville South
Recruitment hospital [6] 0 0
Royal Hobart Hospital /ID# 149111 - Hobart
Recruitment hospital [7] 0 0
Box Hill Hospital /ID# 149112 - Box Hill
Recruitment hospital [8] 0 0
Peter MacCallum Cancer Ctr /ID# 149107 - Melbourne
Recruitment hospital [9] 0 0
Alfred Health /ID# 150085 - Melbourne
Recruitment hospital [10] 0 0
Fiona Stanley Hospital /ID# 148967 - Murdoch
Recruitment hospital [11] 0 0
Perth Blood Institute Ltd /ID# 148966 - Nedlands
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2139 - Concord
Recruitment postcode(s) [3] 0 0
2170 - Liverpool
Recruitment postcode(s) [4] 0 0
4029 - Herston
Recruitment postcode(s) [5] 0 0
5011 - Woodville South
Recruitment postcode(s) [6] 0 0
7000 - Hobart
Recruitment postcode(s) [7] 0 0
3128 - Box Hill
Recruitment postcode(s) [8] 0 0
3000 - Melbourne
Recruitment postcode(s) [9] 0 0
3004 - Melbourne
Recruitment postcode(s) [10] 0 0
6150 - Murdoch
Recruitment postcode(s) [11] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
North Carolina
Country [3] 0 0
United States of America
State/province [3] 0 0
Ohio
Country [4] 0 0
Brazil
State/province [4] 0 0
Goias
Country [5] 0 0
Brazil
State/province [5] 0 0
Rio Grande Do Norte
Country [6] 0 0
Brazil
State/province [6] 0 0
Rio Grande Do Sul
Country [7] 0 0
Brazil
State/province [7] 0 0
Sao Paulo
Country [8] 0 0
Brazil
State/province [8] 0 0
Rio de Janeiro
Country [9] 0 0
Canada
State/province [9] 0 0
Ontario
Country [10] 0 0
Canada
State/province [10] 0 0
Quebec
Country [11] 0 0
France
State/province [11] 0 0
Franche-Comte
Country [12] 0 0
France
State/province [12] 0 0
Pays-de-la-Loire
Country [13] 0 0
France
State/province [13] 0 0
Rhone
Country [14] 0 0
France
State/province [14] 0 0
Brest
Country [15] 0 0
France
State/province [15] 0 0
La Tronche
Country [16] 0 0
Germany
State/province [16] 0 0
Berlin
Country [17] 0 0
Germany
State/province [17] 0 0
Dresden
Country [18] 0 0
Germany
State/province [18] 0 0
Hamburg
Country [19] 0 0
Hungary
State/province [19] 0 0
Hajdu-Bihar
Country [20] 0 0
Hungary
State/province [20] 0 0
Somogy
Country [21] 0 0
Hungary
State/province [21] 0 0
Budapest
Country [22] 0 0
Ireland
State/province [22] 0 0
Galway
Country [23] 0 0
Italy
State/province [23] 0 0
Lazio
Country [24] 0 0
Italy
State/province [24] 0 0
Ancona
Country [25] 0 0
Italy
State/province [25] 0 0
Bologna
Country [26] 0 0
Italy
State/province [26] 0 0
Rome
Country [27] 0 0
Italy
State/province [27] 0 0
Turin
Country [28] 0 0
Japan
State/province [28] 0 0
Aichi
Country [29] 0 0
Japan
State/province [29] 0 0
Fukuoka
Country [30] 0 0
Japan
State/province [30] 0 0
Gifu
Country [31] 0 0
Japan
State/province [31] 0 0
Gunma
Country [32] 0 0
Japan
State/province [32] 0 0
Hiroshima
Country [33] 0 0
Japan
State/province [33] 0 0
Hyogo
Country [34] 0 0
Japan
State/province [34] 0 0
Ibaraki
Country [35] 0 0
Japan
State/province [35] 0 0
Kyoto
Country [36] 0 0
Japan
State/province [36] 0 0
Miyagi
Country [37] 0 0
Japan
State/province [37] 0 0
Okayama
Country [38] 0 0
Japan
State/province [38] 0 0
Osaka
Country [39] 0 0
Japan
State/province [39] 0 0
Saitama
Country [40] 0 0
Japan
State/province [40] 0 0
Tochigi
Country [41] 0 0
Japan
State/province [41] 0 0
Tokyo
Country [42] 0 0
Korea, Republic of
State/province [42] 0 0
Gyeonggido
Country [43] 0 0
Korea, Republic of
State/province [43] 0 0
Seoul Teugbyeolsi
Country [44] 0 0
Korea, Republic of
State/province [44] 0 0
Gwangju
Country [45] 0 0
Korea, Republic of
State/province [45] 0 0
Incheon
Country [46] 0 0
Korea, Republic of
State/province [46] 0 0
Seoul
Country [47] 0 0
Russian Federation
State/province [47] 0 0
Kemerovskaya Oblast
Country [48] 0 0
Russian Federation
State/province [48] 0 0
Ryazanskaya Oblast
Country [49] 0 0
Russian Federation
State/province [49] 0 0
Stavropol Skiy Kray
Country [50] 0 0
Russian Federation
State/province [50] 0 0
Moscow
Country [51] 0 0
Russian Federation
State/province [51] 0 0
Omsk
Country [52] 0 0
Russian Federation
State/province [52] 0 0
Samara
Country [53] 0 0
Russian Federation
State/province [53] 0 0
Ufa
Country [54] 0 0
Spain
State/province [54] 0 0
Barcelona
Country [55] 0 0
Spain
State/province [55] 0 0
Madrid
Country [56] 0 0
Spain
State/province [56] 0 0
Valencia
Country [57] 0 0
Taiwan
State/province [57] 0 0
Changhua City, Changhua County
Country [58] 0 0
Taiwan
State/province [58] 0 0
Taichung City
Country [59] 0 0
Taiwan
State/province [59] 0 0
Taipei City
Country [60] 0 0
Ukraine
State/province [60] 0 0
Cherkasy
Country [61] 0 0
Ukraine
State/province [61] 0 0
Dnipro
Country [62] 0 0
Ukraine
State/province [62] 0 0
Kyiv
Country [63] 0 0
United Kingdom
State/province [63] 0 0
England
Country [64] 0 0
United Kingdom
State/province [64] 0 0
London, City Of
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Nottinghamshire
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Blackpool
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Canterbury
Country [68] 0 0
United Kingdom
State/province [68] 0 0
London
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Manchester
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Romford
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Wolverhampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AbbVie
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Genentech, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
ABBVIE INC.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)
When will data be available (start and end dates)?
For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
Available to whom?
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/
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/ourmember/abbvie/


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.