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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03539744




Registration number
NCT03539744
Ethics application status
Date submitted
17/05/2018
Date registered
17/05/2018
Date last updated
8/02/2019

Titles & IDs
Public title
A Study of Venetoclax and Dexamethasone Compared With Pomalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma
Scientific title
A Phase 3, Multicenter, Randomized, Open Label Study of Venetoclax and Dexamethasone Compared With Pomalidomide and Dexamethasone in Subjects With t(11;14)-Positive Relapsed or Refractory Multiple Myeloma
Secondary ID [1] 0 0
M13-494
Universal Trial Number (UTN)
Trial acronym
CANOVA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
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 - Pomalidomide
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Venetoclax

Experimental: Arm 1 VenDex - Venetoclax administered orally once daily (QD) plus dexamethasone administered orally once every week (Q1W) for each 28-day cycle.

Active Comparator: Arm 2 PomDex - Pomalidomide administered orally once daily (QD) on Days 1 - 21 for each 28-day cycle plus dexamethasone administered orally once every week (Q1W) for each 28-day cycle.
Subjects randomized to this arm may elect, if eligible, to receive VenDex therapy (venetoclax administered orally QD plus dexamethasone administered orally Q1W for each 28-day cycle) after documented disease progression per IMWG criteria.


Treatment: Drugs: Pomalidomide
capsule, oral

Treatment: Drugs: Dexamethasone
oral, locally available form

Treatment: Drugs: Venetoclax
tablet; oral

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

Outcomes
Primary outcome [1] 0 0
Progression-Free Survival (PFS) - PFS is defined as the time in days from subject randomization to the date of the first documented progressive disease (PD) or death due to any cause, whichever occurs first.
Timepoint [1] 0 0
Up to approximately 28 months from first randomization
Secondary outcome [1] 0 0
Very Good Partial Response or Better Response Rate (VGPR) - VGPR or better response rate is defined as the proportion of participants with documented stringent complete response (sCR), complete response (CR), or VGPR.
Timepoint [1] 0 0
Up to approximately 28 months from first randomization
Secondary outcome [2] 0 0
Overall Response Rate (ORR) - ORR is defined as the proportion of participants with documented best response (sCR, CR, VGPR or partial response [PR]) prior to first documented PD.
Timepoint [2] 0 0
Up to approximately 28 months from first randomization
Secondary outcome [3] 0 0
Overall survival (OS) - OS is defined as the number of days from the date that the participant was randomized to the date of the participant's death.
Timepoint [3] 0 0
Up to approximately 37 months from first randomization
Secondary outcome [4] 0 0
Duration of response (DOR) - DOR for a participant is defined as the number of days from the date of first documented response (PR or better) to the date of first documented PD or death due to multiple myeloma, whichever occurs first.
Timepoint [4] 0 0
Up to approximately 28 months from first randomization
Secondary outcome [5] 0 0
Time to Disease Progression (TTP) - TTP for a participant is defined as the number of days from the date of randomization to the date of first documented PD or death due to multiple myeloma, whichever occurs first.
Timepoint [5] 0 0
Up to approximately 28 months from first randomization
Secondary outcome [6] 0 0
Time to Response (TTR) - TTR for a participant is defined as the number of days from the date of randomization to the date of first documented response (PR or better).
Timepoint [6] 0 0
Up to approximately 28 months from first randomization
Secondary outcome [7] 0 0
Minimal Residual Disease (MRD) Negativity Rate - MRD defined as the proportion of participants with MRD negativity status. MRD negativity will be defined at 10^-5 threshold as measured by centralized testing of bone marrow aspirate samples by next generation sequencing (NGS).
Timepoint [7] 0 0
Up to approximately 28 months from first randomization
Secondary outcome [8] 0 0
Cmax of Venetoclax - Maximum plasma concentration (Cmax) of venetoclax
Timepoint [8] 0 0
Up to approximately 225 days from initial dose
Secondary outcome [9] 0 0
Trough Concentration (Ctrough) of Venetoclax - Observed plasma concentration at trough (Ctrough) of venetoclax.
Timepoint [9] 0 0
Up to approximately 225 days from initial dose
Secondary outcome [10] 0 0
Change from Baseline in PROMIS Fatigue Score. - Change from baseline in the Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 7a score.
Timepoint [10] 0 0
Up to approximately 28 months from first randomization
Secondary outcome [11] 0 0
Change from Baseline in BPI-SF Worst Pain Score - Change from baseline in the Brief Pain Inventory - Short Form (BPI-SF) worst pain score.
Timepoint [11] 0 0
Up to approximately 28 months from first randomization
Secondary outcome [12] 0 0
Change from Baseline in EORTC QLQ-30 Physical Functioning Score - Change from baseline in the European Organisation for Research and Treatment of Cancer Quality of Life Core 30 Question Questionnaire (EORTC-QLQ-C30) Physical Functioning Score.
Timepoint [12] 0 0
Up to approximately 28 months from first randomization
Secondary outcome [13] 0 0
Change from Baseline in EORTC QLQ-30 Global Health Status/Quality of Life Score - Change from baseline in EORTC QLQ-30 Global Health Status/Quality of Life Score
Timepoint [13] 0 0
Up to approximately 28 months from first randomization

Eligibility
Key inclusion criteria
- Documented diagnosis of multiple myeloma (MM) based on standard IMWG criteria.

- Measurable disease at screening as defined per protocol.

- Has received at least 2 prior lines of therapy as described in the protocol.

- Has had documented disease progression on or within 60 days after completion of the
last therapy.

- Has received at least 2 consecutive cycles of lenalidomide and be refractory to
lenalidomide, as defined per protocol.

- Has received at least 2 consecutive cycles of a proteasome inhibitor (PI).

- Has MM positive for t(11;14).

- An Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to
2.

- Laboratory values (liver, kidney and hematology laboratory values) that meet criteria
as described per protocol.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- History of treatment with venetoclax or another B-Cell Lymphoma (BCL)-2 inhibitor or
pomalidomide.

- History of other active malignancies, including myelodysplastic syndromes (MDS),
within the past 3 years (exceptions described in the protocol).

- Evidence of ongoing graft-versus-host disease (GvHD) if prior stem cell transplant
(SCT).

- Prior treatment with any of the following: allogeneic or syngeneic SCT within 16 weeks
prior to randomization; or autologous SCT within 12 weeks prior to randomization.

- Known meningeal involvement of MM.

- Concurrent conditions as listed in the protocol.

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
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,WA
Recruitment hospital [1] 0 0
Liverpool Hospital /ID# 202431 - Liverpool
Recruitment hospital [2] 0 0
Wollongong Hospital /ID# 205545 - Wollongong
Recruitment hospital [3] 0 0
Icon Cancer Care - Townsville /ID# 206565 - Hyde Park
Recruitment hospital [4] 0 0
Icon Cancer Centre /ID# 205663 - South Brisbane
Recruitment hospital [5] 0 0
The Queen Elizabeth Hospital /ID# 202432 - Woodville
Recruitment hospital [6] 0 0
Perth Blood Institute Ltd /ID# 206649 - Nedlands
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
2500 - Wollongong
Recruitment postcode(s) [3] 0 0
4812 - Hyde Park
Recruitment postcode(s) [4] 0 0
4101 - South Brisbane
Recruitment postcode(s) [5] 0 0
5011 - Woodville
Recruitment postcode(s) [6] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Kentucky
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
South Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
Czechia
State/province [10] 0 0
Brno
Country [11] 0 0
Czechia
State/province [11] 0 0
Ostrava
Country [12] 0 0
France
State/province [12] 0 0
Hauts-de-France
Country [13] 0 0
France
State/province [13] 0 0
Lorraine
Country [14] 0 0
France
State/province [14] 0 0
Rhone
Country [15] 0 0
France
State/province [15] 0 0
Creteil
Country [16] 0 0
France
State/province [16] 0 0
Nantes
Country [17] 0 0
Germany
State/province [17] 0 0
Schleswig-Holstein
Country [18] 0 0
Germany
State/province [18] 0 0
Berlin
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Germany
State/province [19] 0 0
Jena
Country [20] 0 0
Germany
State/province [20] 0 0
Munich
Country [21] 0 0
Germany
State/province [21] 0 0
Wuerzburg
Country [22] 0 0
Greece
State/province [22] 0 0
Attiki
Country [23] 0 0
Greece
State/province [23] 0 0
Patras
Country [24] 0 0
Greece
State/province [24] 0 0
Thessaloniki
Country [25] 0 0
Israel
State/province [25] 0 0
Tel-Aviv
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Israel
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Haifa
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Israel
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Jerusalem
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Israel
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Tel Aviv
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Italy
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Emilia-Romagna
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Italy
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Marche
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Italy
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Piemonte
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Italy
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Rionero in Vulture
Country [33] 0 0
Italy
State/province [33] 0 0
Terni
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Japan
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Aichi
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Japan
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Fukuoka
Country [36] 0 0
Japan
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Gifu
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Japan
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Gunma
Country [38] 0 0
Japan
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Hyogo
Country [39] 0 0
Japan
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Ibaraki
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Japan
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Miyagi
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Japan
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Okayama
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Japan
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Osaka
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Japan
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Tokushima
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Japan
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Tokyo
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Korea, Republic of
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Incheon Gwang Yeogsi
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Korea, Republic of
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Seoul Teugbyeolsi
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Korea, Republic of
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Seoul
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Russian Federation
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Moskva
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Russian Federation
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Moscow
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Russian Federation
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Pyatigorsk
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Russian Federation
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Sankt-peterburg
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Russian Federation
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St. Petersburg
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Singapore
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Central Singapore
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Singapore
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Singapore
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Spain
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Girona
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Spain
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Madrid
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Spain
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Salamanca
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Spain
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Sevilla
Country [59] 0 0
Sweden
State/province [59] 0 0
Norrbottens Lan
Country [60] 0 0
Sweden
State/province [60] 0 0
Vastra Gotalands Lan
Country [61] 0 0
Turkey
State/province [61] 0 0
Adana
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Turkey
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Izmir
Country [63] 0 0
Turkey
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Ankara
Country [64] 0 0
Turkey
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Istanbul
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United Kingdom
State/province [65] 0 0
Glasgow
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United Kingdom
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London
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United Kingdom
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Manchester
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United Kingdom
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Portsmouth
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United Kingdom
State/province [69] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AbbVie
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
A study designed to evaluate the safety and efficacy of venetoclax plus dexamethasone
(VenDex) compared with pomalidomide plus dexamethasone (PomDex) in participants with
t(11;14)-positive Relapsed or Refractory Multiple Myeloma.

Subjects randomized to Arm 2 (PomDex) may elect, if eligible, to receive VenDex therapy after
documented disease progression per International Myeloma Working Group (IMWG) criteria.
Trial website
https://clinicaltrials.gov/show/NCT03539744
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
ABBVIE CALL CENTER
Address 0 0
Country 0 0
Phone 0 0
847.283.8955
Fax 0 0
Email 0 0
abbvieclinicaltrials@abbvie.com
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Not applicable