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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03314181




Registration number
NCT03314181
Ethics application status
Date submitted
11/10/2017
Date registered
19/10/2017

Titles & IDs
Public title
A Study of Combination Therapy With Venetoclax, Daratumumab and Dexamethasone (With and Without Bortezomib) in Participants With Relapsed or Refractory Multiple Myeloma
Scientific title
A Phase 1/2, Multicenter, Dose-Escalation and Expansion Study of Combination Therapy With Venetoclax, Daratumumab and Dexamethasone (With and Without Bortezomib) in Subjects With Relapsed or Refractory Multiple Myeloma
Secondary ID [1] 0 0
2017-002099-26
Secondary ID [2] 0 0
M15-654
Universal Trial Number (UTN)
Trial acronym
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 - Dexamethasone
Treatment: Drugs - Daratumumab
Treatment: Drugs - Venetoclax
Treatment: Drugs - Bortezomib

Experimental: Arm A, Part 1a: VenDd Dose Escalation - Venetoclax (Ven) various doses administered orally, once daily (QD) in combination with daratumumab (D) (1800 mg subcutaneous injection (preferred) or 16 mg/kg intravenous \[IV\]) administered in accordance with prescribing information and dexamethasone (d) (oral or IV) 40 mg weekly (or 20 mg weekly, if necessary, as described in the protocol).

Experimental: Arm B, Part 1b: VenDd Dose Expansion - Venetoclax at a dose determined by the dose-escalation phase, administered orally QD in combination with daratumumab (1800 mg subcutaneous injection (preferred) or 16 mg/kg IV) administered in accordance with prescribing information and dexamethasone (oral or IV) 40 mg weekly (or 20 mg weekly, if necessary, as described in the protocol).

Experimental: Arm D, Part 2a: VenDVd Dose Escalation - Venetoclax at various doses administered orally QD in combination with daratumumab (1800 mg subcutaneous injection (preferred) or 16 mg/kg IV) administered in accordance with prescribing information, bortezomib (1.3 mg/m2 subcutaneous injection \[preferred\] or IV) Cycles 1-8, Days 1, 4, 8 and 11), and dexamethasone (oral or IV) 20 mg Cycles 1 - 3, Days 1, 2, 4, 5, 8, 9, 11,12 and 15; 20 mg Cycles 4-8, Days 1,2,4,5,8,9,11 and 12; 40 mg weekly (or 20 mg weekly, if necessary as described in the protocol) Cycle 9+.

Experimental: Arm E, Part 2b: VenDVd Dose Expansion - Venetoclax at dose determined by the dose-escalation phase, administered orally QD in combination with daratumumab (1800 mg subcutaneous injection (preferred) or 16 mg/kg IV) administered in accordance with prescribing information, bortezomib (1.3 mg/m2 subcutaneous injection) Cycles 1-8, Days 1, 4, 8 and 11, and dexamethasone (oral or IV) 20 mg Cycles 1 - 3, Days 1, 2, 4, 5, 8, 9, 11,12 and 15; 20 mg Cycles 4-8, Days 1,2,4,5,8,9,11 and 12; 40 mg weekly (or 20 mg weekly, if necessary as described in the protocol) Cycle 9+.

Experimental: Arm F: VenDd Dose Expansion - Venetoclax at a pre-determined dose, administered orally QD in combination with daratumumab (1800 mg subcutaneous injection (preferred) or 16 mg/kg IV) administered in accordance with prescribing information and dexamethasone (oral or IV) 40 mg weekly (or 20 mg weekly, if necessary, as described in the protocol).

Experimental: Arm G: VenDd Dose Expansion - Venetoclax at a pre-determined dose, administered orally QD in combination with daratumumab (1800 mg subcutaneous injection (preferred) or 16 mg/kg IV) administered in accordance with prescribing information and dexamethasone (oral or IV) 40 mg weekly (or 20 mg weekly, if necessary, as described in the protocol).

Active comparator: Arm H: DVd Dose - Daratumumab (1800 mg subcutaneous injection (preferred) or 16 mg/kg IV) administered in accordance with prescribing information, bortezomib (1.3 mg/m2 subcutaneous injection) Cycles 1-8: Days 1, 4, 8 and 11, and dexamethasone (oral or IV) 20 mg on Cycles 1 - 3: Days 1, 2, 4, 5, 8, 9, 11,12 and 15; 40 mg weekly (or 20 mg weekly, if necessary as described in the protocol) on Cycles 4-8: Days 1,2,4,5,8,9,11 and 12; 20 mg monthly for Cycles 9+: Day 1


Treatment: Drugs: Dexamethasone
Infusion; Intravenous (IV), or Tablet; Oral

Treatment: Drugs: Daratumumab
Injection; Subcutaneous (preferred), Infusion; Intravenous (IV)

Treatment: Drugs: Venetoclax
Tablet; Oral

Treatment: Drugs: Bortezomib
Injection; Subcutaneous (preferred), Infusion; Intravenous (IV)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Response Rate (ORR)
Timepoint [1] 0 0
Up to approximately 3.5 years after the last participant is enrolled
Primary outcome [2] 0 0
Very Good Partial Response or Better Response Rate (VGPR)
Timepoint [2] 0 0
Up to approximately 3.5 years after the last participant is enrolled
Primary outcome [3] 0 0
Complete Response (CR) or Better Rate
Timepoint [3] 0 0
Up to approximately 3.5 years after the last participant is enrolled
Primary outcome [4] 0 0
Time to Response (TTR)
Timepoint [4] 0 0
Up to approximately 3.5 years after the last participant is enrolled
Primary outcome [5] 0 0
Duration of Response (DOR)
Timepoint [5] 0 0
Up to approximately 3.5 years after the last participant is enrolled
Primary outcome [6] 0 0
Time to Progression (TTP)
Timepoint [6] 0 0
Up to approximately 3.5 years after the last participant is enrolled
Primary outcome [7] 0 0
Progression-Free Survival (PFS)
Timepoint [7] 0 0
Up to approximately 3.5 years after the last participant is enrolled
Primary outcome [8] 0 0
Overall Survival (OS)
Timepoint [8] 0 0
Up to approximately 3.5 years after the last participant is enrolled
Secondary outcome [1] 0 0
Minimal Residual Disease (MRD)
Timepoint [1] 0 0
Up to 12 months after confirmation of Complete Response (CR) or Stringent Complete Response (sCR)
Secondary outcome [2] 0 0
Cmax of Venetoclax
Timepoint [2] 0 0
Up to approximately 1 year
Secondary outcome [3] 0 0
Tmax of Venetoclax
Timepoint [3] 0 0
Up to approximately 1 year
Secondary outcome [4] 0 0
AUC0-24 of Venetoclax
Timepoint [4] 0 0
Up to approximately 1 year

Eligibility
Key inclusion criteria
* Eastern Cooperative Oncology Group (ECOG) performance status <= 2.
* Participant has relapsed or refractory multiple myeloma with documented evidence of progression that occurred during or after the participant's last treatment regimen based on investigator's determination of International Myeloma Working Group (IMWG) criteria.
* Measurable disease confirmed by central lab at Screening, defined by at least 1 of the following: Serum M-protein >= 1.0 g/dL (>= 10 g/L), OR Urine M-protein >= 200 mg/24 hours, OR Serum free light chain (FLC) >= 10 mg/dL, provided serum FLC ratio is abnormal in participants who do not have measurable disease by Serum Protein Electrophoresis (SPEP) or Urine Protein Electrophoresis (UPEP) criteria.
* Participant has received previous multiple myeloma treatment as defined in the protocol.
* Bone marrow aspirate samples have been collected.
* To qualify for Part 1 and 3, the participant must be t(11;14) positive as determined by an analytically validated Fluorescent In Situ Hybridization (FISH) assay per central laboratory testing.
* Participants must have adequate hematologic, renal and hepatic function.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Previous treatment with venetoclax or other B-Cell Lymphoma 2 (BCL-2) inhibitor
* For participants in Parts 1 and 2: Previous treatment with daratumumab or other anti-CD38 therapy. For participants in Part 3: Prior daratumumab or other anti-CD38 antibody therapy exposure that meets ANY of the following criteria:

* Failure to achieve at least a PR to most recent therapy with daratumumab or other anti-CD38 therapy.
* Daratumumab or other anti-CD38 antibody therapy was discontinued due to toxicity.
* Relapse within 60 days of intensive treatment (at least every other week) of daratumumab or other anti-CD38 antibody therapy.
* Prior treatment with daratumumab or other anti-CD38 antibody within 6 months prior to first dose of study drug.
* For participants in Part 2 and 3:

* 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.
* Treatment with anti-myeloma chemotherapy, radiotherapy, biological, immunotherapy or an investigational therapy, including targeted small molecule agents within 2 weeks or 5 half-lives (whichever is longer and/or applicable) before first dose.
* Treatment with anti-myeloma monoclonal antibodies within 6 weeks prior to first dose.
* Recent corticosteroid therapy at a cumulative dose equivalent to >= 140 mg of prednisone, cumulative dose equivalent to >= 40 mg of dexamethasone, or a single dose equivalent to >= 40 mg of dexamethasone within 2 weeks prior the first dose of study drug.
* Known central nervous system involvement of multiple myeloma.
* Significant history of medical conditions as listed in the protocol.
* History of other active malignancies including myelodysplatic syndromes (MDS) within the past 3 years with the exceptions of:

* 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 confirmed and surgically resected (or treated with other modalities) with curative intent and unlikely to impact survival during the duration of the study.
* Known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
* Has a hypersensitivity or allergy to any of the components of study therapy, excipient or boron.
* Known allergies, hypersensitivities, or intolerance to monoclonal antibodies or human proteins, or their excipients, or known sensitivity to mammalian-derived products (see daratumumab prescribing information).

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 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/04/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
21/08/2025
Actual
Sample size
Target
Accrual to date
Final
156
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
The Kinghorn Cancer Centre /ID# 165431 - Darlinghurst
Recruitment hospital [2] 0 0
St George Hospital /ID# 171063 - Kogarah
Recruitment hospital [3] 0 0
Royal Adelaide Hospital /ID# 171060 - Adelaide
Recruitment hospital [4] 0 0
Eastern Health /ID# 165850 - Box Hill
Recruitment hospital [5] 0 0
St Vincent's Hospital Melbourne /ID# 165853 - Fitzroy Melbourne
Recruitment hospital [6] 0 0
Peter MacCallum Cancer Ctr /ID# 164742 - Melbourne
Recruitment hospital [7] 0 0
Duplicate_Royal Perth Hospital /ID# 224895 - Perth
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3128 - Box Hill
Recruitment postcode(s) [5] 0 0
3065 - Fitzroy Melbourne
Recruitment postcode(s) [6] 0 0
3000 - Melbourne
Recruitment postcode(s) [7] 0 0
6000 - Perth
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
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
New Jersey
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Oregon
Country [10] 0 0
United States of America
State/province [10] 0 0
Washington
Country [11] 0 0
Canada
State/province [11] 0 0
Alberta
Country [12] 0 0
Canada
State/province [12] 0 0
Quebec
Country [13] 0 0
Denmark
State/province [13] 0 0
Hovedstaden
Country [14] 0 0
Denmark
State/province [14] 0 0
Midtjylland
Country [15] 0 0
Denmark
State/province [15] 0 0
Syddanmark
Country [16] 0 0
France
State/province [16] 0 0
Franche-Comte
Country [17] 0 0
France
State/province [17] 0 0
Indre-et-Loire
Country [18] 0 0
France
State/province [18] 0 0
Pays-de-la-Loire
Country [19] 0 0
France
State/province [19] 0 0
Val-de-Marne
Country [20] 0 0
France
State/province [20] 0 0
Vienne
Country [21] 0 0
France
State/province [21] 0 0
Paris
Country [22] 0 0
Germany
State/province [22] 0 0
Baden-Wuerttemberg
Country [23] 0 0
Germany
State/province [23] 0 0
Cologne
Country [24] 0 0
Japan
State/province [24] 0 0
Aichi
Country [25] 0 0
Japan
State/province [25] 0 0
Chiba
Country [26] 0 0
Japan
State/province [26] 0 0
Ehime
Country [27] 0 0
Japan
State/province [27] 0 0
Gifu

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
Janssen Research & Development, LLC
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?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03314181