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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-004340-30 | EudraCT Number |
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| Name | Class |
|---|---|
| Genentech, Inc; Onyx Therapeutics, Inc. | UNKNOWN |
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A Phase 2, open-label, dose escalation study to evaluate the safety and efficacy of venetoclax in combination with carfilzomib-dexamethasone (Kd) in participants with relapsed or refractory MM and have received 1 to 3 prior lines of therapy.
Part 4 of this study is currently enrolling.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Venetoclax + Carfilzomib + Dexamethasone | Experimental | Part 1: Evaluate the safety and pharmacokinetic profiles while providing information to determine the appropriate doses of venetoclax and carfilzomib (VenKd) to be used in the VenKd combination in approximately 18 participants. The dose levels are Venetoclax 400 mg or 800 mg; Carfilzomib 20/27 mg/m2, 20/70 mg/m2, and/or 20/56 mg/m2; Dexamethasone 40 mg Part 2: Further evaluate the safety and efficacy profile of the VenKd combination selected after completion of Part 1 in approximately 22 additional participants. Participants may discontinue Kd but may continue receiving venetoclax once daily (QD) as monotherapy. Part 3: Further evaluation of the efficacy of the VenKd combination after completion of Part 1 and Part 2 in 7 additional participants. Part 4, An additional 65 participants t(11;14) positive will receive varying doses of the VenKd combination or carfilzomib and dexamethasone |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Carfilzomib | Drug | Carfilzomib lyophilized administered intravenously as a 10 to 30 minute infusion in Cycles 1 and beyond within 30 minutes to 4 hours after dexamethasone dosing. Dose level 1 (K1) Cycle 1: 20 mg/m2 on Days 1 and 2, 27 mg/m2 on Days 8, 9, 15, and 16; Cycles 2 - 12: 27 mg/m2 on Days 1, 2, 8, 9, 15, and 16; Cycles 13 - 18: 27 mg/m2 on Days 1, 2, 15, and 16; Cycles 19 and beyond, for participants that have not previously transitioned to monotherapy: 27 mg/m2 on Days 1, 2, 15, and 16. Dose Level K2: Cycle 1: 20 mg/m2 on Day 1; 70 mg/m2 on Days 8 and 15 Cycles 2 - onward: 70 mg/m2 on Days 1, 8, and 15. Dose Level K3: Cycle 1: 20 mg/m2 on Days 1 and 2; 56 mg/m2 on Days 8, 9, 15, and 16. Cycles 2 - onward: 56 mg/m2 on Days 1, 2, 8, 9, 15, and 16. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants with Adverse Events | An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. | First dose of study drug through at least 30 days after end of treatment (approximately 2 years) |
| Very Good Partial Response (VGPR) or Better Response Rate of VenKd in Participants with Relapsed or Refractory Multiple Myeloma (RRMM) as well as Those with t(11;14)-positive RRMM | VGPR or better response rate is defined as the percentage of participants with documented VGPR or better based on IMWG criteria. | First dose of study drug through at least 30 days after end of treatment (approximately 2 years) |
| Objective Response Rate (ORR) of VenKd in Participants with Relapsed or Refractory Multiple Myeloma (RRMM) as well as Those with t(11;14)-positive RRMM | ORR is defined as the percentage of participants with a documented PR or better based on IMWG criteria. | First dose of study drug through at least 30 days after end of treatment (approximately 2 years) |
| Complete Response (CR) or Better Rate of VenKd in Participants with Relapsed or Refractory Multiple Myeloma (RRMM) as well as Those with t(11;14)-positive RRMM | Complete response or better rate is defined as the percentage of participants with documented CR or better based on IMWG criteria. | First dose of study drug through at least 30 days after end of treatment (approximately 2 years) |
| Measure | Description | Time Frame |
|---|---|---|
| Very Good Partial Response (VGPR) or Better Response Rate in Participants with Relapsed or Refractory Multiple Myeloma and in a Subset of Participants with High B-cell lymphocyte-2 (BCL-2) Expression | VGPR or better response rate is defined as the proportion of participants with documented VGPR or better based on IMWG criteria. | Up to approximately 17 months |
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Inclusion Criteria:
Exclusion Criteria:
Has a pre-existing condition that is contraindicated including.
History of other active malignancies, including myelodysplastic syndrome (MDS), within the past 3 years prior to study entry Other protocol defined inclusion/exclusion criteria could apply
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| Name | Affiliation | Role |
|---|---|---|
| ABBVIE INC. | AbbVie | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham - Main /ID# 151405 | Birmingham | Alabama | 35233 | United States | ||
| University of Arkansas for Medical Sciences /ID# 151399 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39388024 | Derived | Badawi MA, Engelhardt B, Dobkowska E, Deng R, Kaufman JL, Menon R, Salem AH. Exposure-response relationships of venetoclax in combination with carfilzomib and dexamethasone in relapsed/refractory t(11;14) multiple myeloma patients. Invest New Drugs. 2024 Dec;42(6):635-643. doi: 10.1007/s10637-024-01471-x. Epub 2024 Oct 10. | |
| 34470049 |
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AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information.
For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
To learn more about the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
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| Venetoclax | Drug | Venetoclax tablet administered orally once daily during Cycles 1 - onward. Venetoclax dose level 1 (Ven1) 400 mg once daily, Ven2 800 mg once daily. |
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| Dexamethasone | Drug | Dexamethasone tablet administered orally during Cycles 1 - onward. Dexamethasone dose level 1 (Dex1) 40 mg once weekly, Dex2 40 mg once weekly, Dex3 20 mg twice weekly. |
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| Progression-free survival (PFS) in Participants with Relapsed or Refractory Multiple Myeloma and in a Subset of Participants with High B-cell lymphocyte-2 (BCL-2) Expression | PFS is defined as the number of days from the date of the first dose of study drug to the date of the first documented progressive disease (PD) or death due to any cause, whichever occurs first. | Up to approximately 17 months |
| Minimal residual disease (MRD) | MRD in the bone marrow by next generation sequencing. | Up to 2 years (Screening, Cycle 3 Day 1, and Confirmation of Stringent Complete Response [sCR]/Complete Response [CR]) |
| Duration of Overall Response (DOR) in Participants with Relapsed or Refractory Multiple Myeloma and in a Subset of Participants with High B-cell lymphocyte-2 (BCL-2) Expression | 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 PD or death due to MM, whichever occurs first. | Up to approximately 17 months |
| Time to progression (TTP) in Participants with Relapsed or Refractory Multiple Myeloma and in a Subset of Participants with High B-cell lymphocyte-2 (BCL-2) Expression | TTP is defined as the number of days from the date of the first dose of study drug to the date of first documented PD or death due to MM, whichever occurs first. | Up to approximately 17 months |
| Objective response rate (ORR) in Participants with Relapsed or Refractory Multiple Myeloma and in a Subset of Participants with High B-cell lymphocyte-2 (BCL-2) Expression | ORR is defined as the proportion of participants with documented partial response (PR) or better based on International Myeloma Working Group (IMWG) criteria. | Up to approximately 17 months |
| Time to Response (TTR) in Participants with Relapsed or Refractory Multiple Myeloma and in a Subset of Participants with High B-cell lymphocyte-2 (BCL-2) Expression | TTR is defined as the number of days from the date of the first dose of study drug to the date of first documented response (Partial Response (PR) or better). | Up to approximately 17 months |
| Area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) post-dose of Venetoclax | AUC0-24 post-dose of venetoclax. | Approximately 24 hours post-dose on Cycle 1 Days 1 and 15 |
| Clearance (CL) of Carfilzomib | CL of carfilzomib. | Approximately 4 hours post-dose on Cycle 1 Days 1 and 15 |
| Terminal Phase Elimination Rate Constant (β) of Carfilzomib | β of carfilzomib. | Approximately 4 hours post-dose on Cycle 1 Days 1 and 15 |
| AUC from 0 to Infinity (AUC∞) of Carfilzomib | AUC∞ of carfilzomib. | Approximately 4 hours post-dose on Cycle 1 Days 1 and 15 |
| AUC from Time 0 to the Time of the Last Measurable Concentration (AUCt) of Carfilzomib | AUCt of carfilzomib. | Approximately 4 hours post-dose on Cycle 1 Days 1 and 15 |
| Maximum Plasma Concentration (Cmax) of Venetoclax | Cmax of venetoclax. | Approximately 24 hours post-dose on Cycle 1 Days 1 and 15 |
| Cmax of Carfilzomib | Cmax of carfilzomib. | Approximately 4 hours post-dose on Cycle 1 Days 1 and 15 |
| Terminal Elimination Half-life (t1/2) of Carfilzomib | t1/2 of carfilzomib. | Approximately 4 hours post-dose on Cycle 1 Days 1 and 15 |
| Time to Maximum Plasma Concentration (Peak Time, Tmax) of Venetoclax | (Peak time, Tmax) of venetoclax. | Approximately 24 hours post-dose on Cycle 1 Days 1 and 15 |
| Little Rock |
| Arkansas |
| 72205 |
| United States |
| Memorial Healthcare System /ID# 224862 | Hollywood | Florida | 33021-3513 | United States |
| Winship Cancer Institute of Emory University /ID# 161710 | Atlanta | Georgia | 30322 | United States |
| The University of Chicago Medical Center /ID# 151395 | Chicago | Illinois | 60637-1443 | United States |
| Indiana Blood & Marrow Transpl /ID# 218862 | Indianapolis | Indiana | 46237 | United States |
| Duplicate_University of Kentucky Chandler Medical Center /ID# 151407 | Lexington | Kentucky | 40536 | United States |
| Central Maine Medical Center /ID# 218856 | Lewiston | Maine | 04240 | United States |
| Duplicate_University of Maryland School of Medicine /ID# 159721 | Baltimore | Maryland | 21201-1544 | United States |
| Oncology Hematology Associates (OHA) - Springfield /ID# 218855 | Springfield | Missouri | 65807-5287 | United States |
| Washington University-School of Medicine /ID# 222651 | St Louis | Missouri | 63110 | United States |
| Duke Cancer Center /ID# 162062 | Durham | North Carolina | 27710-3000 | United States |
| University of Pennsylvania /ID# 151768 | Philadelphia | Pennsylvania | 19104-5502 | United States |
| University of Texas Southwestern Medical Center /ID# 218336 | Dallas | Texas | 75390-7208 | United States |
| Baylor Scott & White Medical Center- Temple /ID# 218252 | Temple | Texas | 76508-0001 | United States |
| University of Utah /ID# 151397 | Salt Lake City | Utah | 84112-5500 | United States |
| Duplicate_VA Puget Sound Healthcare Syst /ID# 155369 | Seattle | Washington | 98108 | United States |
| Aurora Health Care, Aurora Cancer Center /ID# 209612 | Wauwatosa | Wisconsin | 53226-3436 | United States |
| Border Medical Oncology Research Unit Albury Wodonga Regiona /ID# 222200 | East Albury | New South Wales | 2640 | Australia |
| Calvary Mater Newcastle /ID# 218739 | Waratah | New South Wales | 2298 | Australia |
| Flinders Medical Centre /ID# 221345 | Bedford Park | South Australia | 5042 | Australia |
| Royal Hobart Hospital /ID# 217546 | Hobart | Tasmania | 7000 | Australia |
| Debreceni Egyetem-Klinikai Kozpont /ID# 217624 | Debrecen | Hajdú-Bihar | 4032 | Hungary |
| Semmelweis Egyetem /ID# 217626 | Budapest | 1085 | Hungary |
| Del-pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet /ID# 217625 | Budapest | 1097 | Hungary |
| Szegedi Tudományegyetem /ID# 219172 | Szeged | 6720 | Hungary |
| Auxilio Mutuo Cancer Center /ID# 157853 | San Juan | 00918 | Puerto Rico |
| VA Caribbean Healthcare System /ID# 157854 | San Juan | 00921-3201 | Puerto Rico |
| Hospital Universitario Germans Trias i Pujol /ID# 218006 | Badalona | Barcelona | 08916 | Spain |
| Hospital Clinic de Barcelona /ID# 218007 | Barcelona | 08036 | Spain |
| Hospital General Universitario Gregorio Maranon /ID# 218005 | Madrid | 28007 | Spain |
| Hospital Universitario Ramon y Cajal /ID# 220925 | Madrid | 28034 | Spain |
| Costa LJ, Davies FE, Monohan GP, Kovacsovics T, Burwick N, Jakubowiak A, Kaufman JL, Hong WJ, Dail M, Salem AH, Yang X, Masud AA, Munasinghe W, Ross JA, Bueno OF, Kumar SK, Stadtmauer EA. Phase 2 study of venetoclax plus carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma. Blood Adv. 2021 Oct 12;5(19):3748-3759. doi: 10.1182/bloodadvances.2020004146. |
| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| D054219 | Neoplasms, Plasma Cell |
| D012008 | Recurrence |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C524865 | carfilzomib |
| C579720 | venetoclax |
| D003907 | Dexamethasone |
| ID | Term |
|---|---|
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |
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