Multiple Myeloma Clinical Trial

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

View Eligibility Criteria

Eligibility 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).

Study is for people with:

Multiple Myeloma

Phase:

Phase 2

Estimated Enrollment:

156

Study ID:

NCT03314181

Recruitment Status:

Active, not recruiting

Sponsor:

AbbVie

Check Your Eligibility

Let’s see if you might be eligible for this study.

What is your age and gender ?

Submit

There are 38 Locations for this study

See Locations Near You

Univ of Colorado Cancer Center /ID# 167331
Aurora Colorado, 80045, United States
Moffitt Cancer Center /ID# 169614
Tampa Florida, 33612, United States
Emory University, Winship Cancer Institute /ID# 165427
Atlanta Georgia, 30322, United States
The University of Chicago Medical Center /ID# 165429
Chicago Illinois, 60637, United States
Beth Israel Deaconess Medical Center /ID# 210904
Boston Massachusetts, 02215, United States
Dana-Farber Cancer Institute /ID# 166886
Boston Massachusetts, 02215, United States
Hackensack Univ Med Ctr /ID# 225111
Hackensack New Jersey, 07601, United States
Roswell Park Comprehensive Cancer Center /ID# 169615
Buffalo New York, 14263, United States
Weill Cornell Medicine/NYP /ID# 167605
New York New York, 10021, United States
Atrium Health Carolinas Medical Center /ID# 164948
Charlotte North Carolina, 28203, United States
Duke Cancer Center /ID# 165104
Durham North Carolina, 27710, United States
Wake Forest Baptist Health /ID# 224447
Winston-Salem North Carolina, 27157, United States
Oregon Health & Science University /ID# 166822
Portland Oregon, 97239, United States
University of Washington /ID# 164884
Seattle Washington, 98109, United States
The Kinghorn Cancer Centre /ID# 165431
Darlinghurst New South Wales, 2010, Australia
St George Hospital /ID# 171063
Kogarah New South Wales, 2217, Australia
Royal Adelaide Hospital /ID# 171060
Adelaide South Australia, 5000, Australia
Eastern Health /ID# 165850
Box Hill Victoria, 3128, Australia
St Vincent's Hospital Melbourne /ID# 165853
Fitzroy Melbourne Victoria, 3065, Australia
Peter MacCallum Cancer Ctr /ID# 164742
Melbourne Victoria, 3000, Australia
Royal Perth Hospital /ID# 224895
Perth Western Australia, 6000, Australia
Tom Baker Cancer Centre /ID# 167822
Calgary Alberta, T2N 4, Canada
Cross Cancer Institute /ID# 203114
Edmonton Alberta, T6G 1, Canada
Royal Victoria Hospital / McGill University Health Centre /ID# 167824
Montreal Quebec, H4A 3, Canada
Rigshospitalet /ID# 164420
Copenhagen Ø Hovedstaden, 2100, Denmark
Aarhus University Hospital /ID# 164509
Aarhus N Midtjylland, 8200, Denmark
Odense University Hospital /ID# 164417
Odense C Syddanmark, 5000, Denmark
Sygehus Lillebælt, Vejle /ID# 164418
Vejle Syddanmark, 7100, Denmark
CHU Limoges - Dupuytren 1 /ID# 224759
Limoges CEDEX 1 Franche-Comte, 87042, France
CHRU Tours - Hopital Bretonneau /ID# 164795
Tours CEDEX 9 Indre-et-Loire, 37044, France
CHU de Nantes, Hotel Dieu -HME /ID# 164767
Nantes Pays-de-la-Loire, 44000, France
CHU Poitiers - La milétrie /ID# 164806
Poitiers Poitou-Charentes, 86000, France
Institut Gustave Roussy /ID# 164807
Villejuif Cedex Val-de-Marne, 94805, France
AP-HP - Hopital Saint-Louis /ID# 224758
Paris , 75010, France
Universitaetsklinikum Freiburg /ID# 166036
Freiburg Baden-Wuerttemberg, 79106, Germany
University Hospital Cologne /ID# 166037
Cologne , 50937, Germany
Nagoya City University Hospital /ID# 225273
Nagoya shi Aichi, 467-8, Japan
Kameda General Hospital /ID# 225246
Kamogawa-shi Chiba, 296-8, Japan
Matsuyama Red Cross Hospital /ID# 225196
Matsuyama-shi Ehime, 790-8, Japan
Gifu Municipal Hospital /ID# 240381
Gifu-shi Gifu, 500-8, Japan

How clear is this clinincal trial information?

Study is for people with:

Multiple Myeloma

Phase:

Phase 2

Estimated Enrollment:

156

Study ID:

NCT03314181

Recruitment Status:

Active, not recruiting

Sponsor:


AbbVie

How clear is this clinincal trial information?

×

Introducing, the Journey Bar

Use this bar to access information about the steps in your cancer journey.

Please confirm you are a US based health care provider:

Yes, I am a health care Provider No, I am not a health care provider