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Multiple MyelomaPhase 2NCT03314181

A Study of Combination Therapy With Venetoclax, Daratumumab and Dexamethasone (With and Without Bortezomib) in Participants With Relapsed or Refractory Multiple Myeloma

A Phase 2 study testing Dexamethasone, Daratumumab and Venetoclax in people with Multiple Myeloma, run by AbbVie at 40 sites in 7 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This is a study of venetoclax, daratumumab, and dexamethasone with and without bortezomib combination therapy to evaluate safety, tolerability, and efficacy of these combinations in participants with relapsed or refractory multiple myeloma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
Dexamethasone, Daratumumab and Venetoclax
Could I receive a placebo?
No, everyone receives an active treatment
How many people
156 participants
Where
40 sitesin 7 countries
Study dates
2 Apr 2018to May 2031
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 21Show fewer
  • 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).

Trial locations and contacts

40 sites in 7 countries.

40 sites in 7 countries

United States14 sites

  • Winship Cancer Institute of Emory University /ID# 165427

    Atlanta, Georgia, 30322

  • Univ of Colorado Cancer Center /ID# 167331

    Aurora, Colorado, 80045

  • Beth Israel Deaconess Medical Center /ID# 210904

    Boston, Massachusetts, 02215-5400

  • Dana-Farber Cancer Institute /ID# 166886

    Boston, Massachusetts, 02215

  • Duplicate_Roswell Park Comprehensive Cancer Center /ID# 169615

    Buffalo, New York, 14263

  • Atrium Health Carolinas Medical Center /ID# 164948

    Charlotte, North Carolina, 28203

  • The University of Chicago Medical Center /ID# 165429

    Chicago, Illinois, 60637-1443

  • Duke Cancer Center /ID# 165104

    Durham, North Carolina, 27710-3000

  • Hackensack Univ Med Ctr /ID# 225111

    Hackensack, New Jersey, 07601

  • Weill Cornell Medicine/NYP /ID# 167605

    New York, New York, 10021-4872

  • Oregon Health and Science University /ID# 166822

    Portland, Oregon, 97239

  • University of Washington /ID# 164884

    Seattle, Washington, 98109

  • Moffitt Cancer Center /ID# 169614

    Tampa, Florida, 33612-9416

  • Duplicate_Wake Forest Baptist Health /ID# 224447

    Winston-Salem, North Carolina, 27157-0001

Other trials in United States

Australia7 sites

  • Duplicate_Royal Adelaide Hospital /ID# 171060

    Adelaide, South Australia, 5000

  • Eastern Health /ID# 165850

    Box Hill, Victoria, 3128

  • The Kinghorn Cancer Centre /ID# 165431

    Darlinghurst, New South Wales, 2010

  • St Vincent's Hospital Melbourne /ID# 165853

    Fitzroy Melbourne, Victoria, 3065

  • St George Hospital /ID# 171063

    Kogarah, New South Wales, 2217

  • Peter MacCallum Cancer Ctr /ID# 164742

    Melbourne, Victoria, 3000

  • Duplicate_Royal Perth Hospital /ID# 224895

    Perth, Western Australia, 6000

Other trials in Australia

France6 sites

  • CHU Limoges - Dupuytren 1 /ID# 224759

    Limoges, Franche-Comte, 87042

  • Centre Hospitalier Universitaire de Nantes, Hotel Dieu -HME /ID# 164767

    Nantes, Pays de la Loire Region, 44000

  • Duplicate_AP-HP - Hopital Saint-Louis /ID# 224758

    Paris, 75010

  • CHU Poitiers - La miletrie /ID# 164806

    Poitiers, Vienne, 86000

  • CHRU Tours - Hopital Bretonneau /ID# 164795

    Tours, Indre-et-Loire, 37044

  • Institut Gustave Roussy /ID# 164807

    Villejuif, Val-de-Marne, 94805

Other trials in France

Denmark4 sites

  • Duplicate_Aarhus University Hospital /ID# 164509

    Aarhus N, Central Jutland, 8200

  • Rigshospitalet /ID# 164420

    Copenhagen Ø, Capital Region, 2100

  • Odense University Hospital /ID# 164417

    Odense, Region Syddanmark, 5000

  • Sygehus Lillebalt, Vejle /ID# 164418

    Vejle, Region Syddanmark, 7100

Other trials in Denmark

Japan4 sites

  • Gifu Municipal Hospital /ID# 240381

    Gifu, Gifu, 500-8323

  • Kameda General Hospital /ID# 225246

    Kamogawa-shi, Chiba, 296-8602

  • Duplicate_Matsuyama Red Cross Hospital /ID# 225196

    Matsuyama, Ehime, 790-8524

  • Nagoya City University Hospital /ID# 225273

    Nagoya, Aichi-ken, 467-8602

Other trials in Japan

Canada3 sites

  • Arthur J. E. Child Comprehensive Cancer Centre /ID# 167822

    Calgary, Alberta, T2N 5G2

  • Cross Cancer Institute /ID# 203114

    Edmonton, Alberta, T6G 1Z2

  • Disc_Royal Victoria Hospital / McGill University Health Centre /ID# 167824

    Montreal, Quebec, H4A 3J1

Other trials in Canada

Germany2 sites

  • University Hospital Cologne /ID# 166037

    Cologne, North Rhine-Westphalia, 50937

  • Universitaetsklinikum Freiburg /ID# 166036

    Freiburg im Breisgau, Baden-Wurttemberg, 79106

Other trials in Germany

About this study

Official 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

This is a study of venetoclax, daratumumab, and dexamethasone with and without bortezomib combination therapy to evaluate safety, tolerability, and efficacy of these combinations in participants with relapsed or refractory multiple myeloma. The study will consist of 3 distinct parts: Part 1 includes participants with t(11;14) positive relapsed/refractory (R/R) multiple myeloma who will receive venetoclax in combination with daratumumab and dexamethasone (VenDd); Part 2 includes participants with R/R multiple myeloma who will receive venetoclax in combination with daratumumab, bortezomib, and dexamethasone (VenDVd); Part 3 includes participants with t(11;14) positive R/R multiple myeloma who will receive venetoclax in combination with daratumumab and dexamethasone (VenDd) or daratumumab, bortezomib, and dexamethasone (DVd).

Part 1 and Part 2 are non-randomized and will be initiated with a dose-escalation phase in which increasing doses of venetoclax will be given with fixed doses of daratumumab and dexamethasone (Part 1a) or with fixed doses of daratumumab, bortezomib, and dexamethasone (Part 2a). Each dose escalation phase will be followed by a single-arm, open-label expansion phase. Part 3 will include a randomized, open-label expansion phase with participants receiving venetoclax in combination with daratumumab and dexamethasone (VenDd) or daratumumab, bortezomib, and dexamethasone (DVd).

Keywords
t(11,14) positive relapsed/refractory (R/R) multiple myeloma, Non-refractory Relapsed Multiple Myeloma, Non-refractory Refractory Multiple Myeloma, Relapsed Multiple Myeloma, Refractory Multiple Myeloma, Multiple Myeloma, Cancer, Venetoclax, Venclexta
Medical subject headings
Multiple Myeloma, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DexamethasoneDrug

    Infusion; Intravenous (IV), or Tablet; Oral

  • DaratumumabDrug

    Injection; Subcutaneous (preferred), Infusion; Intravenous (IV)

  • VenetoclaxDrug

    Also called ABT-199, Venclexta

    Tablet; Oral

  • BortezomibDrug

    Injection; Subcutaneous (preferred), Infusion; Intravenous (IV)

Study groups in NCT03314181
Study groupRoleWhat they receive
Arm A, Part 1a: VenDd Dose EscalationExperimentalVenetoclax (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).
Receives: Drug: Dexamethasone; Drug: Daratumumab; Drug: Venetoclax
Arm B, Part 1b: VenDd Dose ExpansionExperimentalVenetoclax 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).
Receives: Drug: Dexamethasone; Drug: Daratumumab; Drug: Venetoclax
Arm D, Part 2a: VenDVd Dose EscalationExperimentalVenetoclax 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+.
Receives: Drug: Dexamethasone; Drug: Daratumumab; Drug: Venetoclax; Drug: Bortezomib
Arm E, Part 2b: VenDVd Dose ExpansionExperimentalVenetoclax 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+.
Receives: Drug: Dexamethasone; Drug: Daratumumab; Drug: Venetoclax; Drug: Bortezomib
Arm F: VenDd Dose ExpansionExperimentalVenetoclax 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).
Receives: Drug: Dexamethasone; Drug: Daratumumab; Drug: Venetoclax
Arm G: VenDd Dose ExpansionExperimentalVenetoclax 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).
Receives: Drug: Dexamethasone; Drug: Daratumumab; Drug: Venetoclax
Arm H: DVd DoseActive comparatorDaratumumab (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
Receives: Drug: Dexamethasone; Drug: Daratumumab; Drug: Bortezomib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response Rate (ORR)

    ORR is defined as the percentage of participants with documented partial response (PR) or better based on International Myeloma Working Group (IMWG) criteria.

    Measured: Up to approximately 3.5 years after the last participant is enrolled

  2. Very Good Partial Response or Better Response Rate (VGPR)

    VGPR or better response rate is defined as the proportion of participants with documented VGPR or better (sCR, CR. or VGPR) based on IMWG criteria.

    Measured: Up to approximately 3.5 years after the last participant is enrolled

  3. Complete Response (CR) or Better Rate

    CR or better response is defined as the percentage of participants with documented response of CR or better (stringent complete response [sCR] or CR) based on IMWG criteria.

    Measured: Up to approximately 3.5 years after the last participant is enrolled

  4. Time to Response (TTR)

    TTR is defined as the number of days from the date of treatment start (for subjects enrolled prior to randomization start) or randomization (for randomized subjects) to the date of first documented response of PR or better.

    Measured: Up to approximately 3.5 years after the last participant is enrolled

  5. Duration of Response (DOR)

    DOR is defined as the number of days from the participant's date of first documented response (PR or better) to the date of first documented disease progression or death due to multiple myeloma, whichever occurs first.

    Measured: Up to approximately 3.5 years after the last participant is enrolled

  6. Time to Progression (TTP)

    TTP is defined as the number of days from the date of treatment start (for subjects enrolled prior to randomization start) or randomization (for randomized subjects) to the date of first documented PD or death due to MM, whichever occurs first.

    Measured: Up to approximately 3.5 years after the last participant is enrolled

  7. Progression-Free Survival (PFS)

    PFS is defined as the number of days from the date of treatment start (for subjects enrolled prior to randomization start) or randomization (for randomized subjects) to the date of the first documented PD or death due to any cause, whichever occurs first.

    Measured: Up to approximately 3.5 years after the last participant is enrolled

  8. Overall Survival (OS)

    OS is defined as the number of days from the date of treatment start (for subjects enrolled prior to randomization start) or randomization (for randomized subjects) to the date of death.

    Measured: Up to approximately 3.5 years after the last participant is enrolled

Secondary outcomes (4)

  1. Minimal Residual Disease (MRD)

    MRD negativity in bone marrow aspirates is defined at 10^-5 threshold as assessed by next generation sequencing (NGS) in participants at the time of suspected CR/sCR, and at 6 and 12 months post confirmation of CR/sCR for participants who maintained this response.

    Measured: Up to 12 months after confirmation of Complete Response (CR) or Stringent Complete Response (sCR)

  2. Cmax of Venetoclax

    Maximum observed plasma concentration (Cmax) of venetoclax

    Measured: Up to approximately 1 year

  3. Tmax of Venetoclax

    Time to Cmax (Tmax) of Venetoclax

    Measured: Up to approximately 1 year

  4. AUC0-24 of Venetoclax

    Area under the plasma concentration-time curve (AUC) over the dose interval (AUC0-24) of venetoclax.

    Measured: Up to approximately 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Oct 2017
  2. Study start2 Apr 2018
  3. Primary completionMay 2031 (estimated)
  4. Study completionMay 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
156 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03314181
Sponsor's protocol ID
M15-654
Other IDs
2017-002099-26, 2017
Status last verified
Aug 2025
First submitted
11 Oct 2017
Last updated
14 Aug 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information.
Expanded access
Available

Publications

  • Bahlis NJ, Baz R, Harrison SJ, Quach H, Ho SJ, Vangsted AJ, Plesner T, Moreau P, Gibbs SD, Coppola S, Yang X, Al Masud A, Ross JA, Bueno O, Kaufman JL. Phase I Study of Venetoclax Plus Daratumumab and Dexamethasone, With or Without Bortezomib, in Patients With Relapsed or Refractory Multiple Myeloma With and Without t(11;14). J Clin Oncol. 2021 Nov 10;39(32):3602-3612. doi: 10.1200/JCO.21.00443. Epub 2021 Aug 13.

    PubMed 34388020

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dexamethasone, Daratumumab and Venetoclax in people with Multiple Myeloma, run by AbbVie at 40 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 14 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 40 sites in United States, Australia, France, Denmark, Japan and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) (time frame: Up to approximately 3.5 years after the last participant is enrolled). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03314181, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2025.

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