A Study of Combination Therapy With Venetoclax, Daratumumab and Dexamethasone (With and Without Bortezomib) in Participants With Relapsed or Refractory Multiple Myeloma (NCT03314181) — Canada Trial Details

Condition(s) studied

Multiple Myeloma

Investigational drug(s) / intervention(s)

Dexamethasone →Daratumumab →Venetoclax →Bortezomib →

Dexamethasone: Infusion; Intravenous (IV), or Tablet; Oral

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

Venetoclax: Tablet; Oral

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

Study 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).

Eligibility

Sex

ALL

Min age

18 Years

Max age

—

Healthy volunteers

No

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).

Primary outcome measure(s)

Overall Response Rate (ORR) — Up to approximately 3.5 years after the last participant is enrolled
ORR is defined as the percentage of participants with documented partial response (PR) or better based on International Myeloma Working Group (IMWG) criteria.
Very Good Partial Response or Better Response Rate (VGPR) — Up to approximately 3.5 years after the last participant is enrolled
VGPR or better response rate is defined as the proportion of participants with documented VGPR or better (sCR, CR. or VGPR) based on IMWG criteria.
Complete Response (CR) or Better Rate — Up to approximately 3.5 years after the last participant is enrolled
CR or better response is defined as the percentage of participants with documented response of CR or better (stringent complete response \[sCR\] or CR) based on IMWG criteria.
Time to Response (TTR) — Up to approximately 3.5 years after the last participant is enrolled
TTR is defined as the number of days from the date of treatment start (for subjects enrolled prior to randomization start) or randomization (for randomized subjects) to the date of first documented response of PR or better.
Duration of Response (DOR) — Up to approximately 3.5 years after the last participant is enrolled
DOR is defined as the number of days from the participant's date of first documented response (PR or better) to the date of first documented disease progression or death due to multiple myeloma, whichever occurs first.
Time to Progression (TTP) — Up to approximately 3.5 years after the last participant is enrolled
TTP is defined as the number of days from the date of treatment start (for subjects enrolled prior to randomization start) or randomization (for randomized subjects) to the date of first documented PD or death due to MM, whichever occurs first.
Progression-Free Survival (PFS) — Up to approximately 3.5 years after the last participant is enrolled
PFS is defined as the number of days from the date of treatment start (for subjects enrolled prior to randomization start) or randomization (for randomized subjects) to the date of the first documented PD or death due to any cause, whichever occurs first.
Overall Survival (OS) — Up to approximately 3.5 years after the last participant is enrolled
OS is defined as the number of days from the date of treatment start (for subjects enrolled prior to randomization start) or randomization (for randomized subjects) to the date of death.

Trial sites (40)

Facility	City	Region
Univ of Colorado Cancer Center /ID# 167331	Aurora	Colorado
Moffitt Cancer Center /ID# 169614	Tampa	Florida
Winship Cancer Institute of Emory University /ID# 165427	Atlanta	Georgia
The University of Chicago Medical Center /ID# 165429	Chicago	Illinois
Beth Israel Deaconess Medical Center /ID# 210904	Boston	Massachusetts
Dana-Farber Cancer Institute /ID# 166886	Boston	Massachusetts
Hackensack Univ Med Ctr /ID# 225111	Hackensack	New Jersey
Duplicate_Roswell Park Comprehensive Cancer Center /ID# 169615	Buffalo	New York
Weill Cornell Medicine/NYP /ID# 167605	New York	New York
Atrium Health Carolinas Medical Center /ID# 164948	Charlotte	North Carolina
Duke Cancer Center /ID# 165104	Durham	North Carolina
Duplicate_Wake Forest Baptist Health /ID# 224447	Winston-Salem	North Carolina
Oregon Health and Science University /ID# 166822	Portland	Oregon
University of Washington /ID# 164884	Seattle	Washington
The Kinghorn Cancer Centre /ID# 165431	Darlinghurst	New South Wales
St George Hospital /ID# 171063	Kogarah	New South Wales
Duplicate_Royal Adelaide Hospital /ID# 171060	Adelaide	South Australia
Eastern Health /ID# 165850	Box Hill	Victoria
St Vincent's Hospital Melbourne /ID# 165853	Fitzroy Melbourne	Victoria
Peter MacCallum Cancer Ctr /ID# 164742	Melbourne	Victoria
Duplicate_Royal Perth Hospital /ID# 224895	Perth	Western Australia
Arthur J. E. Child Comprehensive Cancer Centre /ID# 167822	Calgary	Alberta
Cross Cancer Institute /ID# 203114	Edmonton	Alberta
Disc_Royal Victoria Hospital / McGill University Health Centre /ID# 167824	Montreal	Quebec
Rigshospitalet /ID# 164420	Copenhagen Ø	Capital Region
Duplicate_Aarhus University Hospital /ID# 164509	Aarhus N	Central Jutland
Odense University Hospital /ID# 164417	Odense	Region Syddanmark
Sygehus Lillebalt, Vejle /ID# 164418	Vejle	Region Syddanmark
CHU Limoges - Dupuytren 1 /ID# 224759	Limoges	Franche-Comte
CHRU Tours - Hopital Bretonneau /ID# 164795	Tours	Indre-et-Loire
Centre Hospitalier Universitaire de Nantes, Hotel Dieu -HME /ID# 164767	Nantes	Pays de la Loire Region
Institut Gustave Roussy /ID# 164807	Villejuif	Val-de-Marne
CHU Poitiers - La miletrie /ID# 164806	Poitiers	Vienne
Duplicate_AP-HP - Hopital Saint-Louis /ID# 224758	Paris	France
Universitaetsklinikum Freiburg /ID# 166036	Freiburg im Breisgau	Baden-Wurttemberg
University Hospital Cologne /ID# 166037	Cologne	North Rhine-Westphalia
Nagoya City University Hospital /ID# 225273	Nagoya	Aichi-ken
Kameda General Hospital /ID# 225246	Kamogawa-shi	Chiba
Duplicate_Matsuyama Red Cross Hospital /ID# 225196	Matsuyama	Ehime
Gifu Municipal Hospital /ID# 240381	Gifu	Gifu

On this site

📄 Darzalex (daratumumab) drug profile → 📄 Venclexta (venetoclax) drug profile →

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