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

Running, not enrolling · Phase 2

Conditions studied: Multiple Myeloma

In brief

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).

Key facts

Study ID: NCT03314181
Run by: AbbVie
People needed: 156
Starts: 2018-04-02
Expected to finish: 2031-05-01
Last updated by the study team: 2025-08-14

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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.

You may not qualify if…

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).

Where it is running

Univ of Colorado Cancer Center /ID# 167331 — Aurora, Colorado, United States
Moffitt Cancer Center /ID# 169614 — Tampa, Florida, United States
Winship Cancer Institute of Emory University /ID# 165427 — Atlanta, Georgia, United States
The University of Chicago Medical Center /ID# 165429 — Chicago, Illinois, United States
Beth Israel Deaconess Medical Center /ID# 210904 — Boston, Massachusetts, United States
Dana-Farber Cancer Institute /ID# 166886 — Boston, Massachusetts, United States
Hackensack Univ Med Ctr /ID# 225111 — Hackensack, New Jersey, United States
Duplicate_Roswell Park Comprehensive Cancer Center /ID# 169615 — Buffalo, New York, United States
Weill Cornell Medicine/NYP /ID# 167605 — New York, New York, United States
Atrium Health Carolinas Medical Center /ID# 164948 — Charlotte, North Carolina, United States
Duke Cancer Center /ID# 165104 — Durham, North Carolina, United States
Duplicate_Wake Forest Baptist Health /ID# 224447 — Winston-Salem, North Carolina, United States
Oregon Health and Science University /ID# 166822 — Portland, Oregon, United States
University of Washington /ID# 164884 — Seattle, Washington, United States
The Kinghorn Cancer Centre /ID# 165431 — Darlinghurst, New South Wales, Australia
St George Hospital /ID# 171063 — Kogarah, New South Wales, Australia
Duplicate_Royal Adelaide Hospital /ID# 171060 — Adelaide, South Australia, Australia
Eastern Health /ID# 165850 — Box Hill, Victoria, Australia
St Vincent's Hospital Melbourne /ID# 165853 — Fitzroy Melbourne, Victoria, Australia
Peter MacCallum Cancer Ctr /ID# 164742 — Melbourne, Victoria, Australia
Duplicate_Royal Perth Hospital /ID# 224895 — Perth, Western Australia, Australia
Arthur J. E. Child Comprehensive Cancer Centre /ID# 167822 — Calgary, Alberta, Canada
Cross Cancer Institute /ID# 203114 — Edmonton, Alberta, Canada
Disc_Royal Victoria Hospital / McGill University Health Centre /ID# 167824 — Montreal, Quebec, Canada
Rigshospitalet /ID# 164420 — Copenhagen Ø, Capital Region, Denmark

Full record on ClinicalTrials.gov

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