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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
156
Infusion; Intravenous (IV), or Tablet; Oral
Injection; Subcutaneous (preferred), Infusion; Intravenous (IV)
Tablet; Oral
Injection; Subcutaneous (preferred), Infusion; Intravenous (IV)
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
Overall Response Rate (ORR)
ORR is defined as the percentage of participants with documented partial response (PR) or better based on International Myeloma Working Group (IMWG) criteria.
Time frame: Up to approximately 3.5 years after the last participant is enrolled
Very Good Partial Response or Better Response Rate (VGPR)
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.
Time frame: Up to approximately 3.5 years after the last participant is enrolled
Complete Response (CR) or Better Rate
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 frame: Up to approximately 3.5 years after the last participant is enrolled
Time to Response (TTR)
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.
Time frame: Up to approximately 3.5 years after the last participant is enrolled
Duration of Response (DOR)
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 frame: Up to approximately 3.5 years after the last participant is enrolled
Time to Progression (TTP)
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.
Time frame: Up to approximately 3.5 years after the last participant is enrolled
Progression-Free Survival (PFS)
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.
Time frame: Up to approximately 3.5 years after the last participant is enrolled
Overall Survival (OS)
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.
Time frame: Up to approximately 3.5 years after the last participant is enrolled
Minimal Residual Disease (MRD)
MRD negativity in bone marrow aspirates is defined at 10\^-5 threshold as assessed by next generation sequencing (NGS) in participants at the time of suspected CR/sCR, and at 6 and 12 months post confirmation of CR/sCR for participants who maintained this response.
Time frame: Up to 12 months after confirmation of Complete Response (CR) or Stringent Complete Response (sCR)
Cmax of Venetoclax
Maximum observed plasma concentration (Cmax) of venetoclax
Time frame: Up to approximately 1 year
Tmax of Venetoclax
Time to Cmax (Tmax) of Venetoclax
Time frame: Up to approximately 1 year
AUC0-24 of Venetoclax
Area under the plasma concentration-time curve (AUC) over the dose interval (AUC0-24) of venetoclax.
Time frame: Up to approximately 1 year
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
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
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