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

Study Purpose

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).

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

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.

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).

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03314181
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

AbbVie
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

ABBVIE INC.
Principal Investigator Affiliation AbbVie
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries Australia, Canada, Denmark, France, Germany, Japan, United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Multiple Myeloma
Study Website: View Trial Website
Arms & Interventions

Arms

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

Interventions

Drug: - Dexamethasone

Infusion; Intravenous (IV), or Tablet; Oral

Drug: - Daratumumab

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

Drug: - Venetoclax

Tablet; Oral

Drug: - Bortezomib

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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Aurora, Colorado

Status

Completed

Address

Univ of Colorado Cancer Center /ID# 167331

Aurora, Colorado, 80045

Moffitt Cancer Center /ID# 169614, Tampa, Florida

Status

Recruiting

Address

Moffitt Cancer Center /ID# 169614

Tampa, Florida, 33612-9416

Site Contact

Site Coordinator

abbvieclinicaltrials@abbvie.com

844-663-3742

Atlanta, Georgia

Status

Recruiting

Address

Emory University, Winship Cancer Institute /ID# 165427

Atlanta, Georgia, 30322

Chicago, Illinois

Status

Recruiting

Address

The University of Chicago Medical Center /ID# 165429

Chicago, Illinois, 60637-1443

Boston, Massachusetts

Status

Completed

Address

Beth Israel Deaconess Medical Center /ID# 210904

Boston, Massachusetts, 02215-5400

Dana-Farber Cancer Institute /ID# 166886, Boston, Massachusetts

Status

Recruiting

Address

Dana-Farber Cancer Institute /ID# 166886

Boston, Massachusetts, 02215

Hackensack Univ Med Ctr /ID# 225111, Hackensack, New Jersey

Status

Recruiting

Address

Hackensack Univ Med Ctr /ID# 225111

Hackensack, New Jersey, 07601

Buffalo, New York

Status

Completed

Address

Roswell Park Comprehensive Cancer Center /ID# 169615

Buffalo, New York, 14263

Weill Cornell Medicine/NYP /ID# 167605, New York, New York

Status

Completed

Address

Weill Cornell Medicine/NYP /ID# 167605

New York, New York, 10021-4872

Charlotte, North Carolina

Status

Recruiting

Address

Atrium Health Carolinas Medical Center /ID# 164948

Charlotte, North Carolina, 28203

Duke Cancer Center /ID# 165104, Durham, North Carolina

Status

Recruiting

Address

Duke Cancer Center /ID# 165104

Durham, North Carolina, 27710-3000

Wake Forest Baptist Health /ID# 224447, Winston-Salem, North Carolina

Status

Recruiting

Address

Wake Forest Baptist Health /ID# 224447

Winston-Salem, North Carolina, 27157-0001

Portland, Oregon

Status

Recruiting

Address

Oregon Health & Science University /ID# 166822

Portland, Oregon, 97239-3011

University of Washington /ID# 164884, Seattle, Washington

Status

Recruiting

Address

University of Washington /ID# 164884

Seattle, Washington, 98109

International Sites

The Kinghorn Cancer Centre /ID# 165431, Darlinghurst, New South Wales, Australia

Status

Recruiting

Address

The Kinghorn Cancer Centre /ID# 165431

Darlinghurst, New South Wales, 2010

St George Hospital /ID# 171063, Kogarah, New South Wales, Australia

Status

Recruiting

Address

St George Hospital /ID# 171063

Kogarah, New South Wales, 2217

Royal Adelaide Hospital /ID# 171060, Adelaide, South Australia, Australia

Status

Recruiting

Address

Royal Adelaide Hospital /ID# 171060

Adelaide, South Australia, 5000

Eastern Health /ID# 165850, Box Hill, Victoria, Australia

Status

Recruiting

Address

Eastern Health /ID# 165850

Box Hill, Victoria, 3128

Fitzroy Melbourne, Victoria, Australia

Status

Recruiting

Address

St Vincent's Hospital Melbourne /ID# 165853

Fitzroy Melbourne, Victoria, 3065

Peter MacCallum Cancer Ctr /ID# 164742, Melbourne, Victoria, Australia

Status

Recruiting

Address

Peter MacCallum Cancer Ctr /ID# 164742

Melbourne, Victoria, 3000

Royal Perth Hospital /ID# 224895, Perth, Western Australia, Australia

Status

Recruiting

Address

Royal Perth Hospital /ID# 224895

Perth, Western Australia, 6000

Tom Baker Cancer Centre /ID# 167822, Calgary, Alberta, Canada

Status

Recruiting

Address

Tom Baker Cancer Centre /ID# 167822

Calgary, Alberta, T2N 4N2

Cross Cancer Institute /ID# 203114, Edmonton, Alberta, Canada

Status

Recruiting

Address

Cross Cancer Institute /ID# 203114

Edmonton, Alberta, T6G 1Z2

Montreal, Quebec, Canada

Status

Recruiting

Address

Royal Victoria Hospital / McGill University Health Centre /ID# 167824

Montreal, Quebec, H4A 3J1

Rigshospitalet /ID# 164420, Copenhagen Ø, Hovedstaden, Denmark

Status

Recruiting

Address

Rigshospitalet /ID# 164420

Copenhagen Ø, Hovedstaden, 2100

Aarhus University Hospital /ID# 164509, Aarhus N, Midtjylland, Denmark

Status

Completed

Address

Aarhus University Hospital /ID# 164509

Aarhus N, Midtjylland, 8200

Odense University Hospital /ID# 164417, Odense C, Syddanmark, Denmark

Status

Recruiting

Address

Odense University Hospital /ID# 164417

Odense C, Syddanmark, 5000

Sygehus Lillebælt, Vejle /ID# 164418, Vejle, Syddanmark, Denmark

Status

Recruiting

Address

Sygehus Lillebælt, Vejle /ID# 164418

Vejle, Syddanmark, 7100

CHU Limoges - Dupuytren 1 /ID# 224759, Limoges CEDEX 1, Franche-Comte, France

Status

Recruiting

Address

CHU Limoges - Dupuytren 1 /ID# 224759

Limoges CEDEX 1, Franche-Comte, 87042

Tours CEDEX 9, Indre-et-Loire, France

Status

Recruiting

Address

CHRU Tours - Hopital Bretonneau /ID# 164795

Tours CEDEX 9, Indre-et-Loire, 37044

Nantes, Pays-de-la-Loire, France

Status

Recruiting

Address

CHU de Nantes, Hotel Dieu -HME /ID# 164767

Nantes, Pays-de-la-Loire, 44000

CHU Poitiers - La milétrie /ID# 164806, Poitiers, Poitou-Charentes, France

Status

Recruiting

Address

CHU Poitiers - La milétrie /ID# 164806

Poitiers, Poitou-Charentes, 86000

Institut Gustave Roussy /ID# 164807, Villejuif Cedex, Val-de-Marne, France

Status

Recruiting

Address

Institut Gustave Roussy /ID# 164807

Villejuif Cedex, Val-de-Marne, 94805

AP-HP - Hopital Saint-Louis /ID# 224758, Paris, France

Status

Recruiting

Address

AP-HP - Hopital Saint-Louis /ID# 224758

Paris, , 75010

Freiburg, Baden-Wuerttemberg, Germany

Status

Recruiting

Address

Universitaetsklinikum Freiburg /ID# 166036

Freiburg, Baden-Wuerttemberg, 79106

University Hospital Cologne /ID# 166037, Cologne, Germany

Status

Recruiting

Address

University Hospital Cologne /ID# 166037

Cologne, , 50937

Nagoya shi, Aichi, Japan

Status

Recruiting

Address

Nagoya City University Hospital /ID# 225273

Nagoya shi, Aichi, 467-8602

Kameda General Hospital /ID# 225246, Kamogawa-shi, Chiba, Japan

Status

Recruiting

Address

Kameda General Hospital /ID# 225246

Kamogawa-shi, Chiba, 296-8602

Matsuyama Red Cross Hospital /ID# 225196, Matsuyama-shi, Ehime, Japan

Status

Recruiting

Address

Matsuyama Red Cross Hospital /ID# 225196

Matsuyama-shi, Ehime, 790-8524

Gifu Municipal Hospital /ID# 240381, Gifu-shi, Gifu, Japan

Status

Recruiting

Address

Gifu Municipal Hospital /ID# 240381

Gifu-shi, Gifu, 500-8513