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

  • STATUS
    Recruiting
  • End date
    Jun 26, 2025
  • participants needed
    104
  • sponsor
    AbbVie
Updated on 8 September 2021
measurable disease
bone marrow procedure
dexamethasone
bortezomib
electrophoresis
daratumumab
refractory multiple myeloma

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. 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).

Details
Condition Multiple Myeloma, Lymphoproliferative Disorder, Cancer - Multiple Myeloma, Cancer - Multiple Myeloma, Cancer - Multiple Myeloma, Lymphoproliferative disorders, multiple myeloma (mm)
Treatment Placebo, Dexamethasone, Bortezomib, Daratumumab, venetoclax
Clinical Study IdentifierNCT03314181
SponsorAbbVie
Last Modified on8 September 2021

Eligibility

Yes No Not Sure

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 Part 2 and 3
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
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
Daratumumab or other anti-CD38 antibody therapy was discontinued due to toxicity
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
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
Significant history of medical conditions as listed in the protocol
Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin
Treatment with anti-myeloma monoclonal antibodies within 6 weeks prior to first dose
Prostate cancer Gleason grade 6 or lower AND with stable Prostate Specific Antigen (PSA) levels off treatment
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
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 central nervous system involvement of multiple myeloma
History of other active malignancies including myelodysplatic syndromes (MDS) within the past 3 years with the exceptions of
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)
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