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Closed (no longer recruiting)Last updated: 9 January 2024

M15-654: This phase II trial is evaluating the combination of two anti-cancer therapies (Venetoclax and Daratumumab) and a steroid (Dexamethasone), with or without (Bortezomib) chemotherapy in patients with Multiple MyelomaA 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

Clinical summary


This is a non-randomised, dose escalation and expansion trial. In this trial, Venetoclax will be administered orally at varying doses, as determined by the dose-escalation phase. Venetoclax will be administered in combination with Daratumumab (16 mg/kg IV), which will be given in accordance with prescribing information. Bortezomib will be administered via 1.3mg/m2 subcutaneous injection and dexamethasone will be administered orally or by IV, as described in the protocol.


This trial is treating patients with Multiple Myeloma


Blood Cancers Haematological





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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



  • 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.


  • 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).


  • You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.


  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.

Clinical trials have complex eligibility criteria.

Ask your doctor if this trial could be right for you.

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